Abstract

Aging is the greatest risk factor for numerous diseases and mortality, and establishing geroprotective interventions targeting aging is required. Previous studies have suggested that healthy dietary patterns, such as the Mediterranean diet, are associated with delayed biological aging; however, these associations depend on nationality and sex. Therefore, this study aimed to investigate the relationship between dietary patterns identified through principal component analysis and biological aging in older men of Japan, one of the countries with the longest life expectancies. Principal component analysis identified two dietary patterns: a healthy Japanese dietary pattern and a Western-style dietary pattern. Eight epigenetic clocks, some of the most accurate aging biomarkers, were identified using DNA methylation data from whole-blood samples. Correlation analyses revealed that healthy Japanese dietary patterns were significantly negatively or positively correlated with multiple epigenetic age accelerations (AgeAccel), including AgeAccelGrim, FitAgeAccel, and age-adjusted DNAm-based telomere length (DNAmTLAdjAge). Conversely, the Western-style dietary pattern showed no significant correlation with any of the examined epigenetic AgeAccels or age-adjusted values. After adjusting for confounders, the healthy Japanese dietary pattern remained significantly negatively correlated with AgeAccelPheno and AgeAccelGrim and positively correlated with DNAmTLAdjAge. These findings suggest that a Western-style dietary pattern is not associated with biological aging, whereas a healthy Japanese dietary pattern is associated with delayed biological aging in older Japanese men. Our findings provide evidence that healthy dietary patterns may have beneficial effects on delayed biological aging in older Japanese men.

AIMS: High non-fasting triglycerides (TG) concentration is linked to the development of atherosclerosis, and physical activity is commonly recommended to reduce postprandial TG concentration and cardiovascular diseases. Previous studies have demonstrated that acute whole-body (walking and running) or lower-body (leg cycling) aerobic exercise reduces postprandial TG. However, it is unclear whether upper-body exercise (i.e. arm-cranking) with sufficient energy expenditure lowers postprandial TG. Therefore, this study aimed to evaluate the effects of energy-matched upper- and lower-body exercises on postprandial TG concentrations the next day in healthy young men. METHOD AND MATERIALS: Fifteen healthy young men (age 22.5 ± 1.7 years, height 173.8 ± 5.7 cm, body mass 68.2 ± 8.5 kg, peak oxygen uptake 48.0 ± 5.5 mL/min/kg and physically active) participated in a three-arm crossover trials: 1) arm-cranking, 2) leg-cycling exercise at 70% of mode-specific peak oxygen uptake to induce a net energy expenditure of 1,255 kJ, or 3) rested between 16:00 and 17:00 h on day 1 and consumed two standardised meals for breakfast (10:00 h) and lunch (13:00 h) on day 2. The mean macronutrient content of the breakfast was 44.9 ± 5.6 g fat, 104.8 ± 13.0 g carbohydrate, and 29.4 ± 3.6 g protein, which provided 3.95 ± 0.49 MJ energy (43% fat, 45% carbohydrate, and 12% protein), and that of the lunch was 45.2 ± 5.6 g fat, 106.7 ± 13.2 g carbohydrate, and 33.9 ± 4.2 g protein, which provided 4.06 ± 0.50 MJ energy (42% fat, 44% carbohydrate, and 14% protein). RESULTS: Time-averaged postprandial serum TG concentrations over 8 h differed among trials (main effect of trial p < 0.001) and were lower in the upper- and lower-body exercise trials than in the control trial (1.46 ± 0.54 vs. 1.50 ± 0.69 vs. 1.79 ± 0.83 mmol/L, respectively). The incremental TG area under the curve (AUC) (main effect of trial, p = 0.012) was 39% and 37% higher in the control trial than in the upper- and lower-body exercise trials (p = 0.025 and p = 0.033, respectively). There were no significant differences in incremental TG AUC between the upper- and lower-body exercise trials. CONCLUSION: An acute bout of energy-matched upper- and lower-body exercises similarly lowered postprandial TG concentrations the following day in healthy young men.Trial registration number: UMIN000045449.Date of registration: 10 September 2021.

AIM: The gut microbiota has emerged as a new intervention target for sarcopenia. Prior studies in humans have focused on the association between gut microbiota and skeletal muscle quantity, while the evidence on muscle function and quality is lacking. This study aimed to identify gut microbiota genera associated with skeletal muscle function, quantity, and quality in a general population of Japanese adults. METHODS: This cross-sectional study included 164 participants aged 35-80 years, women and men recruited from urban areas of Japan. Fecal samples were collected and analyzed using 16S rRNA gene amplicon sequencing. Skeletal muscle function was measured using handgrip strength and leg extension power (LEP), while skeletal muscle mass was estimated using bioelectrical impedance analysis. Phase angle was used as a measure of skeletal muscle quality. Multivariate linear regression analysis stratified by age group was used to examine the association between the dominant genera of the gut microbiota and skeletal muscle variables. RESULTS: A significant association was found between Bacteroides and Prevotella 9 with LEP only in the ≥60 years group. When both Bacteroides and Prevotella 9 were included in the same regression model, only Bacteroides remained consistently and significantly associated with LEP. No significant associations were observed between skeletal muscle mass, handgrip strength, and phase angle and major gut microbiota genera. CONCLUSIONS: In this study, we observed a significant positive association between Bacteroides and leg muscle function in older adults. Further studies are required to elucidate the underlying mechanisms linking Bacteroides to lower-extremity muscle function. Geriatr Gerontol Int 2023; ••: ••-••.

Escherichia coli harboring polyketide synthase (pks+ E. coli) has been suggested to contribute to colorectal cancer development. Physical activity is strongly associated with lower colorectal cancer risks, but its effects on pks+ E. coli remain unclear. The aim of this study was to investigate the association between pks+ E. coli prevalence and physical activity. A cross-sectional study was conducted on 222 Japanese adults (27-79-years-old, 73.9% female). Triaxial accelerometers were used to measure light-intensity physical activity, moderate-to-vigorous intensity physical activity, the physical activity level, step-count, and time spent inactive. Fecal samples collected from participants were used to determine the prevalence of pks+ E. coli. Multivariate logistic regression analysis and restricted cubic spline curves were used to examine the association between pks+ E. coli prevalence and physical activity. The prevalence of pks+ E. coli was 26.6% (59/222 participants). The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the highest tertile with reference to the lowest tertile of physical activity variables were as follows: light-intensity physical activity (OR 0.63; 95% CI 0.26-1.5), moderate-to-vigorous intensity physical activity (OR 0.85; 95% CI 0.39-1.87), physical activity level (OR 0.69; 95% CI 0.32-1.51), step-count (OR 0.92; 95% CI 0.42-2.00) and time spent inactive (OR 1.30; 95% CI 0.58-2.93). No significant dose-response relationship was found between all physical activity variables and pks+ E. coli prevalence. Our findings did not suggest that physical activity has beneficial effects on the prevalence of pks+ E. coli. Longitudinal studies targeting a large population are needed to clarify this association.

A growing number of companies are developing or using wearable sensor technologies that can monitor, analyse and transmit data from humans in real time that can be used by the sporting, biomedical and media industries. To explore this phenomenon, we describe and review two high-profile sporting events where innovations in wearable technologies were trialled: the Tokyo 2020 Summer Olympic Games (Tokyo 2020, Japan) and the 2022 adidas Road to Records (Germany). These two major sporting events were the first time academic and industry partners came together to implement real-time wearable solutions during major competition, to protect the health of athletes competing in hot and humid environments, as well as to better understand how these metrics can be used moving forwards. Despite the undoubted benefits of such wearables, there are well-founded concerns regarding their use including: (1) limited evidence quantifying the potential beneficial effects of analysing specific parameters, (2) the quality of hardware and provided data, (3) information overload, (4) data security and (5) exaggerated marketing claims. Employment and sporting rules and regulations also need to evolve to facilitate the use of wearable devices. There is also the potential to obtain real-time data that will oblige medical personnel to make crucial decisions around whether their athletes should continue competing or withdraw for health reasons. To protect athletes, the urgent need is to overcome these ethical/data protection concerns and develop wearable technologies that are backed by quality science. The fields of sport and exercise science and medicine provide an excellent platform to understand the impact of wearable sensors on performance, wellness, health, and disease.

Abstract

Purpose:Limited data are available on the relationship of parasympathetic nervous function with the prevalence of prediabetes and diabetes in men and women. We conducted a cross-sectional study to investigate the relationship between diving reflex - markers of parasympathetic nervous function - with the prevalence of prediabetes and diabetes among men and women in WASEDA'S Health Study.Methods: Participants were 199 men and 75 women who completed a medical examination, maximal exercise test, and diving reflex test. The participants were divided into tertiles based on the diving reflex indexes. The diving reflex indexes were the peak value of the R–R interval during the test (R–Rmax) and the relative difference between the baseline and peak response due to the test (R–Rchange). Odds ratios and 95% confidence intervals for the prevalence of prediabetes and diabetes were obtained using logistic regression models while adjusting for sex, age, body fat percentage, family history of diabetes, smoking status, and drinking status, sleeping hours, energy intake, and peak oxygen uptake.Results: Forty-one participants had prediabetes (n=24) or diabetes (n=17). Using the lowest diving reflex indexes as reference, we calculated odds ratios and 95% confidence intervals for the outcomes if interests. We found inverse relationships between R-Rmax and prediabetes and diabetes (P for trend = 0.104) as well as R-Rchange and diabetes (P for trend = 0.023).Conclusions: In this cross-sectional analysis, the data suggest diving reflex indexes, especially R-Rchange, may be related to the prevalence of diabetes.

AIM: Aging decreases muscle mass and bone mineral density (BMD), especially in older women. It has been reported that rowing and inulin intake positively affect muscle and bone, respectively. We examined the synergistic effect of rowing and functional food intake, including inulin, on lean body mass, BMD, and physical function parameters in older Japanese women. METHODS: Fifty women aged 65-79 years were divided into four groups with or without inulin intake and rowing. The interventions were carried out for 12 weeks in each group. We assessed lean body mass and BMD using dual-energy X-ray absorptiometry at baseline and after the intervention and examined the changes in the values in each group. RESULTS: Lean body mass in all groups decreased, and the change in lean body mass in the group with rowing and inulin intake was significantly smaller than that in the group without them (-0.05 ± 0.61; -0.83 ± 0.59 kg; P = 0.030). The BMD in the three intervention groups increased after the 12-week intervention. The change in BMD in each of the three intervention groups showed significant differences compared with the control group (Rowing + Inulin: P = 0.03; Rowing + No inulin: P = 0.01; No rowing + Inulin: P < 0.01). CONCLUSIONS: Rowing and the intake of functional foods, including inulin, synergistically prevented a decrease in lean body mass. These factors, individually and additively, might increase BMD in older Japanese women. Geriatr Gerontol Int 2023; ••: ••-••.

Ageing is associated with a decline in circadian clock systems, which correlates with the development of ageing-associated diseases. Chrononutrition is a field of chronobiology that examines the relationship between the timing of meal/nutrition and circadian clock systems. Although there is growing evidence regarding the role of chrononutrition in the prevention of lifestyle and ageing-related diseases, the optimal timing of meal intake to regulate the circadian clock in humans remains unknown. In this study, we investigated the relationship between clock gene expression and meal timing in young and older adults. In this cross-sectional study, we enrolled 51 healthy young men and 35 healthy older men (age, mean±standard deviation: 24 ± 4 and 70 ± 4 y, respectively). Under daily living conditions, beard follicle cells were collected at 4-h intervals over a 24-h period to evaluate clock gene expression. Participants were asked to record the timing of habitual sleep and wake-up, breakfast, lunch, and dinner. From these data, we calculated "From bedtime to breakfast time," "From wake up to first meal time," and "From dinner to bed time." NR1D1 and PER3 expressions in older adults at 06:00 h were significantly higher than those in young adults (P = 0.001). There were significant differences in the peak time for NR1D2 (P = 0.003) and PER3 (P = 0.049) expression between young and older adults. "From bedtime to breakfast time" was significantly longer in older adults than in young adults. In contrast, "From dinner to bed time" was significantly shorter in older adults than in young adults. Moreover, higher rhythmicity of NR1D1 correlated with longer "From bedtime to breakfast time" (r =  -0.470, P = 0.002) and shorter "From wake up to first meal time" in young adults (r = 0.302, P = 0.032). Higher rhythmicity of PER3 correlated with longer "From bedtime to breakfast time" in older adults (r =  -0.342, P = 0.045). These results suggest that the peak time of clock gene expression in older adults may be phase-advanced compared to that in young adults. In addition, a longer fasting duration from bedtime to breakfast in both young and older adults and earlier intake of meals after waking up in young adults may correlate with robust clock gene expression rhythms.

Abstract

DNA methylation-based age estimators (DNAm aging clocks) are currently one of the most promising biomarkers for predicting biological age. However, the relationships between objectively measured physical fitness, including cardiorespiratory fitness, and DNAm aging clocks are largely unknown. We investigated the relationships between physical fitness and the age-adjusted value from the residuals of the regression of DNAm aging clock to chronological age (DNAmAgeAcceleration: DNAmAgeAccel) and attempted to determine the relative contribution of physical fitness variables to DNAmAgeAccel in the presence of other lifestyle factors. DNA samples from 144 Japanese men aged 65–72 years were used to calculate first- (i.e., DNAmHorvath and DNAmHannum) and second- (i.e., DNAmPhenoAge, DNAmGrimAge and DNAmFitAge) generation DNAm aging clocks. Various surveys and measurements were conducted, including physical fitness, body composition, blood biochemical parameters, nutrients intake, smoking, alcohol consumption, disease status, sleep status, and chronotype. The peak oxygen uptake (VO_2peak) per kg body weight had a significant negative correlation with GrimAgeAccel (r= -0.222,p= 0.008). A comparison of the tertile groups showed that the GrimAgeAccel of the highest VO_2peakgroup was decelerated by 1.6 years compared to the lowest group (p= 0.035). Multiple regression analysis suggested that rather than physical fitness, serum triglycerides, carbohydrate intake, and smoking status, were significantly associated with DNAmAgeAccel. In conclusion, the contribution of cardiorespiratory fitness to DNAmAgeAccel was relatively low compared to lifestyle factors such as smoking. However, this study reveals a negative relationship between cardiorespiratory fitness and DNAmAgeAccel in older men.

A cross-sectional study involving 224 healthy Japanese adult females explored the relationship between ramen intake, gut microbiota diversity, and blood biochemistry. Using a stepwise regression model, ramen intake was inversely associated with gut microbiome alpha diversity after adjusting for related factors, including diets, Age, BMI, and stool habits (β = −0.018; r = −0.15 for Shannon index). The intake group of ramen was inversely associated with dietary nutrients and dietary fiber compared with the no-intake group of ramen. Sugar intake, Dorea as a short-chain fatty acid (SCFA)-producing gut microbiota, and γ-glutamyl transferase as a liver function marker were directly associated with ramen intake after adjustment for related factors including diets, gut microbiota, and blood chemistry using a stepwise logistic regression model, whereas Dorea is inconsistently less abundant in the ramen group. In conclusion, the increased ramen was associated with decreased gut bacterial diversity accompanying a perturbation of Dorea through the dietary nutrients, gut microbiota, and blood chemistry, while the methodological limitations existed in a cross-sectional study. People with frequent ramen eating habits need to take measures to consume various nutrients to maintain and improve their health, and dietary management can be applied to the dietary feature in ramen consumption.

Although social jetlag (SJL) is generally considered a chronic condition, even acute SJL may have unfavorable effects on the cardiovascular system. We focused on the acute effects of SJL on morning blood pressure (BP) surge. This randomized crossover trial recruited 20 healthy men. In the SJL trial, participants delayed their bedtime by three hours on Friday and Saturday nights. Participants in the control (CON) trial implemented the same sleep-wake timing as on weekdays. Pre- and post-intervention measurements were performed to evaluate resting cardiovascular variables on Friday and Monday mornings, respectively. The ambulatory BP was automatically measured during the sleep and awake periods for 2 h after the participant woke up at night before pre- and post-intervention measurements. SJL (average mid-sleep time on weekends - average mid-sleep time on weekdays) occurred only in the SJL trial (SJL: 181 ± 24 min vs. CON: 8 ± 47 min). Carotid-femoral pulse wave velocity (cfPWV) and morning BP surge on Monday in the SJL trial were significantly higher than those on Friday in the SJL trial (cfPWV: P = 0.001, morning BP surge: P < 0.001), and those on Monday in the CON trial (cfPWV: P = 0.007; morning BP surge: P < 0.001). Furthermore, a significant positive correlation was found between ΔcfPWV and Δmorning BP surge (R = 0.587, P = 0.004). These results suggest that even acute SJL augments morning BP surge. This phenomenon may correspond to increased central arterial stiffness.State the details of Clinical Trials: Name: Effect of acute social jetlag on risk factors of lifestyle-related diseases. URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053204 . Unique identifier: UMIN000046639. Registration date: 17/01/2022.

Fat-free mass (FFM) is a heterogeneous compartment comprising body cell mass (BCM), intracellular water (ICW), extracellular solids, and extracellular water (ECW). The BCM/FFM and ECW/ICW ratios vary among individuals and decrease with age. This study aimed to determine whether BCM/FFM and ECW/ICW ratios are predictors of maximal oxygen uptake (V̇O2peak) independently of age, sex, and objectively measured physical activity (PA). A total of 115 Japanese males and females, aged 55.3 ± 8.0 years (mean ± standard deviation), were included in the study. Anthropometry, explosive leg muscle power, and V̇O2peak were measured, and BCM, FFM, ICW, and ECW were estimated. Step count and PA were objectively measured using a triaxial accelerometer. Blood flow volume was assessed using ultrasonography. BCM and ICW were negatively correlated with age, whereas FFM and ECW were not significantly correlated with age. FFM, ICW/ECW, BCM/FFM, step counts, moderate and vigorous PA, and leg muscle power were positively correlated with V̇O2peak, even after adjusting for age and sex (P<0.05). Multiple regression analysis indicated that either BCM/FFM or ECW/ICW, leg power, and objectively measured PA were associated with V̇O2peak independent of age, sex, and FFM. Blood flow volume was significantly correlated with ECW (P<0.05), but not with BCM. The BCM/FFM and ECW/ICW ratios were significant predictors of VO2peak, independent of age, sex, FFM, leg power, and objectively measured PA.

Abstract

DNAmPhenoAge, DNAmGrimAge, and the newly developed DNAmFitAge are DNA methylation (DNAm) based biomarkers that reflect the individual aging process. Furthermore, physical fitness is known to relate to the aging process, but its relationship to the gut microbiome has not yet been studied. Here, we examine the relationship among physical fitness, DNAm based biomarkers, and the microbiome in adults aged 33-88 with a wide range of physical fitness (including athletes with long-term training history). Higher levels of VO2max (ρ=0.2, p=6.4E-4, r=0.19, p=1.2E-3), Jumpmax p=0.11, p=5.5E-2, r=0.13 p= 2.8E-2), Gripmax (=ρ=0.17, p=3.5E-3, r=0.16, p=5.6E-3), and HDL levels (ρ=0.18, p=1.95E-3, r=0.19, p=1.1E-3) are associated with better verbal short term memory. In addition, verbal short term memory is associated with decelerated aging assessed with the new DNAm biomarker FitAgeAcceleration (ρ: −0.18, p=0.0017). DNAmFitAge is able to distinguish high fitness individuals from low/medium fitness individuals better than existing DNAm biomarkers and estimates a younger biological age in the high fit males and females (1.5 and 2.0 years younger, respectively). The microbiomal pathways are associated with VO2max, redox balance, and DNAmPhenoAge. PhenoAge Acceleration is influenced by pyruvate producing microbiomal pathways, where higher activity of these pathways lead to suppressed PhenoAge acceleration. Our research shows that regular physical exercise contributes to observable physiological, methylation, and microbiota differences which are beneficial to the aging process. DNAmFitAge emerged as a biological marker of the quality of life.

BACKGROUND: The effects of Anabolic Androgenic Steroids (AAS) are largely illustrated through Androgen Receptor induced gene transcription, yet RNA-Seq has yet to be conducted on human whole blood and skeletal muscle. Investigating the transcriptional signature of AAS in blood may aid AAS detection and in muscle further understanding of AAS induced hypertrophy. METHODS: Males aged 20-42 were recruited and sampled once: sedentary controls (C), resistance trained lifters (RT) and resistance trained current AAS users (RT-AS) who ceased exposure ≤ 2 or ≥ 10 weeks prior to sampling. RT-AS were sampled twice as Returning Participants (RP) if AAS usage ceased for ≥ 18 weeks. RNA was extracted from whole blood and trapezius muscle samples. RNA libraries were sequenced twice, for validation purposes, on the DNBSEQ-G400RS with either standard or CoolMPS PE100 reagents following MGI protocols. Genes were considered differentially expressed with FDR < 0.05 and a 1.2- fold change. RESULTS: Cross-comparison of both standard reagent whole blood (N = 55: C = 7, RT = 20, RT-AS ≤ 2 = 14, RT-AS ≥ 10 = 10, RP = 4; N = 46: C = 6, RT = 17, RT-AS ≤ 2 = 12, RT-AS ≥ 10 = 8, RP = 3) sequencing datasets, showed that no genes or gene sets/pathways were differentially expressed between time points for RP or between group comparisons of RT-AS ≤ 2 vs. C, RT, or RT-AS ≥ 10. Cross-comparison of both muscle (N = 51, C = 5, RT = 17, RT-AS ≤ 2 = 15, RT-AS ≥ 10 = 11, RP = 3) sequencing (one standard & one CoolMPS reagent) datasets, showed one gene, CHRDL1, which has atrophying potential, was upregulated in RP visit two. In both muscle sequencing datasets, nine differentially expressed genes, overlapped with RT-AS ≤ 2 vs. RT and RT-AS ≤ 2 vs. C, but were not differentially expressed with RT vs. C, possibly suggesting they are from acute doping alone. No genes seemed to be differentially expressed in muscle after the long-term cessation of AAS, whereas a previous study found long term proteomic changes. CONCLUSION: A whole blood transcriptional signature of AAS doping was not identified. However, RNA-Seq of muscle has identified numerous differentially expressed genes with known impacts on hypertrophic processes that may further our understanding on AAS induced hypertrophy. Differences in training regimens in participant groupings may have influenced results. Future studies should focus on longitudinal sampling pre, during and post-AAS exposure to better control for confounding variables.

Cellular senescence is greatly accelerated by telomere shortening, and the steps forward in human aging are strongly influenced by environmental and lifestyle factors, whether DNA methylation (DNAm) is affected by exercise training, remains unclear. In the present study, we investigated the relationships between physiological functions, maximal oxygen uptake (VO2max), vertical jump, working memory, telomere length (TL) assessed by RT-PCR, DNA methylation-based estimation of TL (DNAmTL), and DNA methylation-based biomarkers of aging of master rowers (N = 146) and sedentary subjects (N = 95), aged between 37 and 85 years. It was found that the TL inversely correlated with chronological age. We could not detect an association between telomere length and VO2max, vertical jump, and working memory by RT-PCR method, while these physiological test results showed a correlation with DNAmTL. DNAmGrimAge and DNAmPhenoAge acceleration were inversely associated with telomere length assessed by both methods. It appears that there are no strong beneficial effects of exercise or physiological fitness on telomere shortening, however, the degree of DNA methylation is associated with telomere length.

The interaction between the gut and brain is a great puzzle since it is mediated by very complex mechanisms. Therefore, the possible interactions of the brain-exercise-intestine-microbiome axis were investigated in a control (C, N = 6) and voluntarily exercised (VE, N = 8) middle-aged rats. The endurance capacity was assessed by VO2max on the treadmill, spatial memory by the Morris maze test, gastrointestinal motility by EMG, the microbiome by 16S RNA gene amplicon sequencing, caveolae by electron microscopy, and biochemical assays were used to measure protein levels and production of reactive oxygen species (ROS). Eight weeks of voluntary running increased VO2max, and spatial memory was assessed by the Morris maze test but did not significantly change the motility of the gastrointestinal tract or production of ROS in the intestine. The protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) protein levels significantly increased in the intestine, while peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), mitochondrial transcription factor A (TFAM), nuclear respiratory factor 1 (NFR1), SIRT1, SIRT3, nicotinamide phosphoribosyl transferase (NAMPT), and nuclear factor κB (NF-κB) did not change. On the other hand, voluntary exercise increased the number of caveolae in the smooth muscles of the intestine and relative abundance of Bifidobacteria in the microbiome, which correlated with the Akt levels in the intestine. Voluntary exercise has systemic effects and the relationship between intestinal Akt and the microbiome of the gastrointestinal tract could be an important adaptive response.

Factors associated with dynamic changes in the objectively measured physical activity have not been well understood. We aimed to 1) evaluate the longitudinal change in the physical activity trajectory according to sex which is associated with age and to 2) determine the factors associated with the dynamic change in physical activity-related variables across a wide age range among Japanese adults. This longitudinal prospective study included 689 Japanese adults (3914 measurements) aged 26-85 years, whose physical activity data in at least two surveys were available. Physical activity-related variables, such as intensity (inactive, light [LPA; 1.5 to 2.9 metabolic equivalents (METs)], moderate-to-vigorous [MVPA; ≥3.0 METs]), total energy expenditure (TEE), physical activity level (PAL), and step count, were evaluated using a validated triaxial accelerometer. Statistical analysis involved the latent growth curve models and random-effect panel data multivariate regression analysis. During a mean follow-up period of 6.8 years, physical activity was assessed an average of 5.1 times in men and 5.9 times in women. The profiles for the inactive time, LPA (only men), MVPA, step count, PAL, and TEE showed clear curvature, indicating an accelerated rate of change around the age of 70. In contrast, other variables exhibited minimal or no curvature over the age span. The MVPA trajectory was positively associated with alcohol consumption, hand grips, leg power, and trunk flexibility and negatively associated with age, local area, body mass index (BMI), comorbidity score, and heart rate over time. Our results indicated that the physical activity trajectory revealed clear curvature, accelerated rate of change around the age of 70, and determined physical health and fitness and BMI as dynamic factors associated with physical activity changes. These findings may be useful to help support populations to achieve and maintain the recommended level of physical activity.

The phase angle (PhA), measured via bioelectrical impedance analysis, is considered an indicator of cellular health, where higher values reflect higher cellularity, cell membrane integrity, and better cell function. This study aimed to examine the relationship between PhA and exercise habits or objectively measured physical activity. We included 115 people aged 32-69 years. The body composition and PhA were measured using a bioelectrical impedance device. Physical activity and sedentary behavior (SB) were assessed using a triaxial accelerometer. Exercise habits were also obtained through structured interviews, and participants were categorized into the no exercise habit (No-Ex), resistance training exercise habit (RT), or aerobic training exercise habit (AT) groups. Objectively measured moderate-to-vigorous physical activity or step count significantly correlated with PhA, independent of age, sex, height, percent body fat, body cell mass, and leg muscle power. In contrast, SB was not significant determinants of PhA. People who exercised regularly (RT or AT) had significantly higher PhA values than did those in the No-Ex group. Furthermore, the PhA was not significantly different between the RT and AT groups. Regularly engaging in exercise with moderate-to-vigorous intensity may improve or maintain muscle cellular health and muscle quality.

Abstract

Few studies have examined the association between coffee consumption and muscle mass; their results are conflicting. Therefore, we examined the association between coffee consumption and low muscle mass prevalence. We also performed an exploratory investigation of the potential effect modification by demographic, health status-related, and physical activity-related covariates. This cross-sectional study included 2085 adults aged 40–87 years. The frequency of coffee consumption was assessed using a self-administered questionnaire. Muscle mass was assessed as appendicular skeletal muscle mass/height² using a multifrequency bioelectrical impedance analyser. We defined low muscle mass using cut-offs recommended by the Asian Working Group for Sarcopenia. Multivariable-adjusted odds ratios for low muscle mass prevalence were estimated using a logistic regression model. The prevalence of low muscle mass was 5.4% (n = 113). Compared with the lowest coffee consumption group (&lt;1 cup/week), the multivariable-adjusted odds ratios (95% confidence intervals) of low muscle mass prevalence were 0.62 (0.30, 1.29) for 1–3 cups/week, 0.53 (0.29, 0.96) for 4–6 cups/week or 1 cup/day, and 0.28 (0.15, 0.53) for ≥2 cups/day (P for trend &lt;0.001). There were no significant interactions among the various covariates after Bonferroni correction. In conclusion, coffee consumption may be inversely associated with low muscle mass prevalence.

Abstract

The gut microbiome is an important determinant in various diseases. Here we perform a cross-sectional study of Japanese adults and identify the Blautia genus, especially B. wexlerae, as a commensal bacterium that is inversely correlated with obesity and type 2 diabetes mellitus. Oral administration of B. wexlerae to mice induce metabolic changes and anti-inflammatory effects that decrease both high-fat diet–induced obesity and diabetes. The beneficial effects of B. wexlerae are correlated with unique amino-acid metabolism to produce S-adenosylmethionine, acetylcholine, and l-ornithine and carbohydrate metabolism resulting in the accumulation of amylopectin and production of succinate, lactate, and acetate, with simultaneous modification of the gut bacterial composition. These findings reveal unique regulatory pathways of host and microbial metabolism that may provide novel strategies in preventive and therapeutic approaches for metabolic disorders.

The gut microbiota is closely related to good health; thus, there have been extensive efforts dedicated to improving health by controlling the gut microbial environment. Probiotics and prebiotics are being developed to support a healthier intestinal environment. However, much work remains to be performed to provide effective solutions to overcome individual differences in the gut microbial community. This study examined the importance of nutrients, other than dietary fiber, on the survival of gut bacteria in high-health-conscious populations. We found that vitamin B1, which is an essential nutrient for humans, had a significant effect on the survival and competition of bacteria in the symbiotic gut microbiota. In particular, sufficient dietary vitamin B1 intake affects the relative abundance of Ruminococcaceae, and these bacteria have proven to require dietary vitamin B1 because they lack the de novo vitamin B1 synthetic pathway. Moreover, we demonstrated that vitamin B1 is involved in the production of butyrate, along with the amount of acetate in the intestinal environment. We established the causality of possible associations and obtained mechanical insight, through in vivo murine experiments and in silico pathway analyses. These findings serve as a reference to support the development of methods to establish optimal intestinal environment conditions for healthy lifestyles.

OBJECTIVE: It remains unknown whether myonuclei remain elevated post anabolic-androgenic steroid (AAS) usage in humans. Limited data exist on AAS-induced changes in gene expression. DESIGN: Cross-sectional/longitudinal. SETTING: University. PARTICIPANTS: Fifty-six men aged 20 to 42 years. INDEPENDENT VARIABLES: Non-resistance-trained (C) or resistance-trained (RT), RT currently using AAS (RT-AS), of which if AAS usage ceased for ≥18 weeks resampled as Returning Participants (RP) or RT previously using AAS (PREV). MAIN OUTCOME MEASURES: Myonuclei per fiber and cross-sectional area (CSA) of trapezius muscle fibers. RESULTS: There were no significant differences between C (n = 5), RT (n = 15), RT-AS (n = 17), and PREV (n = 6) for myonuclei per fiber. Three of 5 returning participants (RP1-3) were biopsied twice. Before visit 1, RP1 ceased AAS usage 34 weeks before, RP2 and RP3 ceased AAS usage ≤2 weeks before, and all had 28 weeks between visits. Fiber CSA decreased for RP1 and RP2 between visits (7566 vs 6629 μm2; 7854 vs 5677 μm2) while myonuclei per fiber remained similar (3.5 vs 3.4; 2.5 vs 2.6). Respectively, these values increased for RP3 between visits (7167 vs 7889 μm2; 2.6 vs 3.3). CONCLUSIONS: This cohort of past AAS users did not have elevated myonuclei per fiber values, unlike previous research, but reported AAS usage was much lower. Training and AAS usage history also varied widely among participants. Comparable myonuclei per fiber numbers despite decrements in fiber CSA postexposure adheres with the muscle memory mechanism, but there is variation in usage relative to sampling date and low numbers of returning participants.

BACKGROUND: Although the negative relationship between cardiorespiratory fitness (CRF) or muscular fitness and diabetes mellitus were respectively observed in many previous studies, there is still a lack of studies that include CRF and muscular fitness simultaneously. Therefore, this study aimed to investigate the relationship between the combination of CRF and muscular fitness and diabetes through a cross-sectional study.  METHODS: This study was part of WASEDA'S Health Study, a cohort study launched in 2014. We used a part of the baseline data collected for this study. Maximal exercise test using a cycle ergometer and leg extension power (LEP) test were respectively used to evaluate CRF and muscular fitness. Since LEP is affected by body weight, relative LEP (rLEP) which is LEP per body weight, was used as an index of muscular fitness. 796 men (56.5 ± 10.4 years old) who completed a medical examination and fitness tests, were divided into two groups based on CRF and rLEP, respectively. The prevalence of diabetes was collected based on a self-reported questionnaire or blood test. Odds ratios and 95% confidence intervals (CIs) for the prevalence of diabetes were obtained using logistic regression models while adjusting for age, body mass index, exercise habits, family history of diabetes, smoking habits, and drinking habits. RESULTS: 55 (7%) participants had diabetes. Compared to participants with lower CRF or rLEP, the odds ratio (95% CIs) of diabetes in those with higher CRF or rLEP was 0.46 (0.21-0.98) or 0.34 (0.16-0.74), respectively. Furthermore, using the lower CRF and lower rLEP group as the reference, the odds ratio (95% CIs) for the lower CRF and higher rLEP group was 0.32 (0.12-0.88), and higher CRF and higher rLEP group was 0.21 (0.07-0.63), after adjusting for potential confounding factors. CONCLUSIONS: CRF and rLEP have independent and joint inverse associations with diabetes prevalence. In addition, participants with high CRF and high rLEP had a lower prevalence of diabetes compared to those with only high CRF or only high rLEP.

Although many studies have reported that a posteriori dietary pattern is associated with metabolic health, there is little evidence of an association between dietary patterns and different metabolic phenotypes. The present study aimed to examine the association between major dietary patterns and different metabolic phenotypes (metabolically healthy non-obese [MHNO], metabolically unhealthy non-obese [MUNO], metabolically healthy obese [MHO], and metabolically unhealthy obese [MUO]) in middle-aged and elderly Japanese adults. This cross-sectional study enrolled 2,170 Japanese adults aged ≥40 years. The four different metabolic phenotypes were determined based on the presence of obesity, abdominal obesity, hypertension, hyperglycemia, and dyslipidemia. The major dietary patterns were determined using principal component analysis based on energy-adjusted food intake. Two dietary patterns were identified: the healthy dietary pattern, which was characterized by a high intake of vegetables, fruits, potatoes, soy products, mushrooms, seaweeds, and fish; and the alcohol dietary pattern, which was characterized by a high intake of alcoholic beverages, liver, chicken, and fish. The healthy dietary pattern was associated with the MHNO and MHO phenotypes (MUNO and MUO as reference groups, respectively), and the multivariate-adjusted odds ratios (ORs) (95% confidence intervals [CIs]) in the highest quartile of healthy dietary pattern score with the lowest quartile as the reference category were 2.10 (1.40-3.15) and 1.86 (1.06-3.25), respectively. Conversely, the alcohol dietary pattern was inversely associated with the MHNO and MHO phenotypes, while the multivariate-adjusted ORs (95% CIs) in the highest quartile of the alcohol dietary pattern score with the lowest quartile as the reference category were 0.63 (0.42-0.94) and 0.45 (0.26-0.76), respectively. There were no significant interactions between sex and healthy/alcohol dietary patterns in the prevalence of the MHNO and MHO phenotypes. In conclusion, the present study's findings suggest that major dietary patterns are associated with different metabolic phenotypes in middle-aged and elderly Japanese adults. These findings provide useful evidence for maintaining metabolic health through diet regardless of obesity status.

Background: Many cross-sectional studies have identified modifiable factors such as dietary intake, physique, and physical activity associated with diet quality but were unable to determine how a specific individual's diet quality changes with these factors. These relationships may vary depending on an individual's dietary intake. We aimed to determine the association between temporal changes in diet quality and concurrent changes in dietary intake, body mass index (BMI), and physical activity according to the diet quality trajectory pattern. Methods: This longitudinal prospective study included 697 Japanese adults aged 26-85 years, at baseline, with available data from at least two dietary intake surveys (4,118 measurements). Dietary intake and physical activity were evaluated using validated dietary questionnaires and a triaxial accelerometer. Diet quality was calculated using the Nutrient-Rich Food Index 9.3 (NRF9.3), while physical activity was calculated based on the duration of activity performed at each level of intensity (sedentary, light, moderate, and vigorous). Body mass index was calculated from the measured height and weight. Statistical analyses involved latent class growth models (LCGM) and random-effect panel data analysis. Results: During a mean follow-up period of 6.8 years, NRF9.3 scores were assessed, on average, 5.4 times in men and 6.1 times in women. Based on the NRF9.3 score, three separate trajectory groups-"low-increasing," "medium-increasing," and "high-stable"-among individuals aged 26-90 years were identified using LCGM. In the multivariate analysis, the NRF9.3 score trajectory was positively associated with intake of energy, protein, dietary fiber, vitamins A and C, magnesium, and food items, such as fruits and vegetables, and was negatively associated with BMI and the intake of added sugar, saturated fats, sodium, and food items, such as meat and sugar and confectioneries, even after adjusting for covariates. These relationships displayed heterogeneity across the identified NRF9.3 score trajectory groups. In the low-increasing group, an inverse relationship was observed between sedentary behavior and NRF9.3 score trajectory. Conclusions: We identified modifiable factors associated with temporal changes in diet quality across a wide age range; however, these factors may vary according to the diet quality trajectories. Our findings may help develop effective strategies for improving diet quality, according to the trajectory of diet quality.

Millions of consumer sport and fitness wearables (CSFWs) are used worldwide, and millions of datapoints are generated by each device. Moreover, these numbers are rapidly growing, and they contain a heterogeneity of devices, data types, and contexts for data collection. Companies and consumers would benefit from guiding standards on device quality and data formats. To address this growing need, we convened a virtual panel of industry and academic stakeholders, and this manuscript summarizes the outcomes of the discussion. Our objectives were to identify (1) key facilitators of and barriers to participation by CSFW manufacturers in guiding standards and (2) stakeholder priorities. The venues were the Yale Center for Biomedical Data Science Digital Health Monthly Seminar Series (62 participants) and the New England Chapter of the American College of Sports Medicine Annual Meeting (59 participants). In the discussion, stakeholders outlined both facilitators of (e.g., commercial return on investment in device quality, lucrative research partnerships, and transparent and multilevel evaluation of device quality) and barriers (e.g., competitive advantage conflict, lack of flexibility in previously developed devices) to participation in guiding standards. There was general agreement to adopt Keadle et al.'s standard pathway for testing devices (i.e., benchtop, laboratory, field-based, implementation) without consensus on the prioritization of these steps. Overall, there was enthusiasm not to add prescriptive or regulatory steps, but instead create a networking hub that connects companies to consumers and researchers for flexible guidance navigating the heterogeneity, multi-tiered development, dynamicity, and nebulousness of the CSFW field.

BACKGROUND & AIMS: A limited number of studies have developed simple anthropometric equations that can be implemented for predicting muscle mass in the local community. Several studies have suggested calf circumference as a simple and accurate surrogate maker for muscle mass. We aimed to develop and cross-validate a simple anthropometric equation, which incorporates calf circumference, to predict appendicular skeletal muscle mass (ASM) using dual-energy X-ray absorptiometry (DXA). Furthermore, we conducted a comparative validity assessment of our equation with bioelectrical impedance analysis (BIA) and two previously reported equations using similar variables. METHODS: ASM measurements were recorded for 1262 participants (837 men, 425 women) aged 40 years or older. Participants were randomly divided into the development or validation group. Stepwise multiple linear regression was applied to develop the DXA-measured ASM prediction equation. Parameters including age, sex, height, weight, waist circumference, and calf circumference were incorporated as predictor variables. Total error was calculated as the square root of the sum of the square of the difference between DXA-measured and predicted ASMs divided by the total number of individuals. RESULTS: The most optimal ASM prediction equation developed was: ASM (kg) = 2.955 × sex (men = 1, women = 0) + 0.255 × weight (kg) - 0.130 × waist circumference (cm) + 0.308 × calf circumference (cm) + 0.081 × height (cm) - 11.897 (adjusted R2 = 0.94, standard error of the estimate = 1.2 kg). Our equation had smaller total error and higher intraclass correlation coefficient (ICC) values than those for BIA and two previously reported equations, for both men and women (men, total error = 1.2 kg, ICC = 0.91; women, total error = 1.1 kg, ICC = 0.80). The correlation between DXA-measured ASM and predicted ASM by the present equation was not significantly different from the correlation between DXA-measured ASM and BIA-measured ASM. CONCLUSIONS: The equation developed in this study can predict ASM more accurately as compared to equations where calf circumference is used as the sole variable and previously reported equations; it holds potential as a reliable and an effective substitute for estimating ASM.

BACKGROUND: In an effort to increase people's adherence to active lifestyles, contemporary physical activity (PA) guidelines now include low-dose PA. METHODS: PA was evaluated in 583 participants of the Nutritional and Physical Activity Intervention Study (NEXIS) cohort (30-65 years old); 349 inactive participants (MVPA, 2.7 ± 1.0 MET-h/day) were randomly assigned to the intervention or control groups, and 235 active participants participated in follow-up visits. The intervention aimed to increase MVPA and comprised five brief counseling sessions over 1 year. The 1-year target for the participant was increasing their step-count to 10,000 steps/d or +3000 steps/d, relative to the baseline score. The counseling sessions were designed to stimulate progressive changes in physical behaviors by recommendations promoting small and/or light-intensity bouts of PA. PA was measured at baseline, the end of the intervention, and 1 year after the intervention ended. Additionally, several nutrition, health, and fitness parameters were measured. RESULTS: Participants in the intervention group significantly increased their step-count from 8415 ± 1924 at baseline to 9493 ± 2575 at the end of the 1-year period. During the same period, MVPA significantly increased by 0.9 MET-h. The daily time spent in ≥ 3, ≥ 4 and ≥ 5 MET activities increased by 11, 6, and 3 min, respectively. This increase in PA remained observable 1 year after intervention concluded. The active group maintained higher physical activity levels throughout the two years. The intervention group showed smaller energy intakes at the end of the 2-year period. Significant correlations were noted between the 1-year change in MVPA and the change in resting heart rate (r =  - 0.22), and between the 2-year change in MVPA and the change in waist circumference (r =  - 0.08) and peak oxygen consumption capacity (r = 0.23) in the intervention group only. CONCLUSIONS: A prolonged and progressive PA intervention promoting small bouts of light-to-moderate PA may be used in healthy, not-optimally-active people to increase PA beyond the strict period of the intervention. Further studies are necessary to understand whether low-dose PA messages can be effective in initiating a progressive increase toward larger amounts of PA. TRIAL REGISTRATION: Clinical Trials.gov, NCT00926744, retrospectively registered.

PURPOSE: We aimed to investigate the hypothesis that type I collagen plays a role in increasing bone mineral density (BMD) and muscle stiffness, leading to low and high risks of fatigue fracture and muscle injury, respectively, in athletes. As a potential mechanism, we focused on the effect of the type I collagen alpha 1 chain gene (COL1A1) variant associated with transcriptional activity on bone and skeletal muscle properties. METHODS: The association between COL1A1 rs1107946 and fatigue fracture/muscle injury was evaluated in Japanese athletes. Effects of the polymorphism on tissue properties (BMD and muscle stiffness) and type I collagen α1/α2 chain ratios in muscles were examined in Japanese non-athletes. RESULTS: The C allele carrier frequency was greater in female athletes with fatigue fracture than in those without (odds ratio [OR]: 2.44, 95% confidence interval [CI]: 1.17-5.77) and lower in female athletes with muscle injury than in those without (OR: 0.46, 95% CI: 0.24-0.91). Prospective validation analysis confirmed that in female athletes, muscle injury was less frequent in C allele carriers than in AA genotype carriers (Multivariable adjusted hazard ratio: 0.27, 95% CI: 0.08-0.96). Among female non-athletes, the C allele of rs1107946 was associated with lower BMD and lower muscle stiffness. Muscle biopsy revealed that C allele carriers tended to have a larger type I collagen α1/α2 chain ratio than AA genotype carriers (2.24 vs. 2.05, P = 0.056), suggesting a higher proportion of type I collagen α1 homotrimers. CONCLUSION: The COL1A1 rs1107946 polymorphism exerts antagonistic effects on fatigue fracture and muscle injury among female athletes by altering the properties of these tissues, potentially owing to increased levels of type I collagen α1 chain homotrimers.

Rapid advances in wearable technologies and real-time monitoring have resulted in major inroads in the world of recreational and elite sport. One such innovation is the application of real-time monitoring, which comprises a smartwatch application and ecosystem, designed to collect, process and transmit a wide range of physiological, biomechanical, bioenergetic and environmental data using cloud-based services. We plan to assess the impact of this wireless technology during Tokyo2020, where this technology could help characterize the physiological and thermal strain experienced by an athlete, as well as determine future management of athletes during a medical emergency as a result of a more timely and accurate diagnosis. Here we describe some of the innovative technologies developed for numerous sports at Tokyo2020 ranging from race walking (20 km and 50 km events), marathon, triathlon, road cycling (including the time trial event), mountain biking, to potentially team sports played outdoors. A more symbiotic relationship between sport, health and technology needs to be encouraged that harnesses the unique demands of elite sport (e.g., the need for unobtrusive devices that provide real-time feedback) and serves as medical and preventive support for the athlete's care. The implementation of such applications would be particularly welcome in the field of medicine (i.e., telemedicine applications) and the workplace (with particular relevance to emergency services, the military and generally workers under extreme environmental conditions). Laboratory and field-based studies are required in simulated scenarios to validate such emerging technologies, with the field of sport serving as an excellent model to understand and impact disease.

The association between a dietary pattern characterised by high alcohol intake and dyslipidaemia has not been fully investigated. Therefore, the present study aimed to investigate the association between alcohol dietary patterns and the prevalence of dyslipidaemia and its components. This cross-sectional study enrolled 2,171 men and women aged ≥40 years who were alumni of a Japanese university. To identify dietary patterns, a principal component analysis was performed based on the energy-adjusted food intake estimated by a brief-type self-administered diet history questionnaire. Three dietary patterns were identified, the second of which was named the alcohol dietary pattern and was characterised by a high intake of alcoholic beverages, liver, chicken, and fish. This alcohol dietary pattern was associated with reduced low-density lipoprotein cholesterol (LDL-C) levels. The fully adjusted odds ratios (95% confidence intervals) of high LDL-C for the lowest through highest quartile of alcohol dietary pattern score were 1.00 (reference), 0.83 (0.64-1.08), 0.84 (0.64-1.10), and 0.68 (0.49- 0.94), respectively. Subgroup analysis showed that the alcohol dietary pattern was inversely associated with the prevalence of dyslipidaemia in women, whereas it was positively associated with high triglyceride levels in men. In conclusion, the alcohol dietary pattern, characterised by a high intake of alcoholic beverages, liver, chicken, and fish, was associated with the prevalence of dyslipidaemia and its components. This finding provides useful information for the prevention and treatment of dyslipidaemia by modifying the diet.

Sport is historically designated by the binary categorization of male and female that conflicts with modern society. Sport's governing bodies should consider reviewing rules determining the eligibility of athletes in the female category as there may be lasting advantages of previously high testosterone concentrations for transwomen athletes and currently high testosterone concentrations in differences in sex development (DSD) athletes. The use of serum testosterone concentrations to regulate the inclusion of such athletes into the elite female category is currently the objective biomarker that is supported by most available scientific literature, but it has limitations due to the lack of sports performance data before, during or after testosterone suppression. Innovative research studies are needed to identify other biomarkers of testosterone sensitivity/responsiveness, including molecular tools to determine the functional status of androgen receptors. The scientific community also needs to conduct longitudinal studies with specific control groups to generate the biological and sports performance data for individual sports to inform the fair inclusion or exclusion of these athletes. Eligibility of each athlete to a sport-specific policy needs to be based on peer-reviewed scientific evidence made available to policymakers from all scientific communities. However, even the most evidence-based regulations are unlikely to eliminate all differences in performance between cisgender women with and without DSD and transwomen athletes. Any remaining advantage held by transwomen or DSD women could be considered as part of the athlete's unique makeup.

BACKGROUND: Colibactin-producing Escherichia coli containing polyketide synthase (pks+ E. coli) has been shown to be involved in colorectal cancer (CRC) development through gut microbiota analysis in animal models. Stool status has been associated with potentially adverse gut microbiome profiles from fecal analysis in adults. We examined the association between stool patterns and the prevalence of pks+ E. coli isolated from microbiota in fecal samples of 224 healthy Japanese individuals. RESULTS: Stool patterns were determined through factorial analysis using a previously validated questionnaire that included stool frequency, volume, color, shape, and odor. Factor scores were classified into tertiles. The prevalence of pks+ E. coli was determined by using specific primers for pks+ E. coli in fecal samples. Plasma and fecal fatty acids were measured via gas chromatography-mass spectrometry. The prevalence of pks+ E. coli was 26.8%. Three stool patterns identified by factorial analysis accounted for 70.1% of all patterns seen (factor 1: lower frequency, darker color, and harder shape; factor 2: higher volume and softer shape; and factor 3: darker color and stronger odor). Multivariable-adjusted odds ratios (95% confidence intervals) of the prevalence of pks+ E. coli for the highest versus the lowest third of the factor 1 score was 3.16 (1.38 to 7.24; P for trend = 0.006). This stool pattern exhibited a significant positive correlation with fecal isobutyrate, isovalerate, valerate, and hexanoate but showed a significant negative correlation with plasma eicosenoic acid and α-linoleic acid, as well as fecal propionate and succinate. No other stool patterns were significant. CONCLUSIONS: These results suggest that stool patterns may be useful in the evaluation of the presence of tumorigenic bacteria and fecal fatty acids through self-monitoring of stool status without the requirement for specialist technology or skill. Furthermore, it may provide valuable insight about effective strategies for the early discovery of CRC.

BACKGROUND: Inter-individual variations in gut microbiota composition are observed even among healthy populations. The gut microbiota may exhibit a unique composition depending on the country of origin and race of individuals. To comprehensively understand the link between healthy gut microbiota and host state, it is beneficial to conduct large-scale cohort studies. The aim of the present study was to elucidate the integrated and non-redundant factors associated with gut microbiota composition within the Japanese population by 16S rRNA sequencing of fecal samples and questionnaire-based covariate analysis. RESULTS: A total of 1596 healthy Japanese individuals participated in this study via two independent cohorts, NIBIOHN cohort (n = 954) and MORINAGA cohort (n = 642). Gut microbiota composition was described and the interaction of these microorganisms with metadata parameters such as anthropometric measurements, bowel habits, medical history, and lifestyle were obtained. Thirteen genera, including Alistipes, Anaerostipes, Bacteroides, Bifidobacterium, Blautia, Eubacterium halli group, Faecalibacterium, Fusicatenibacter, Lachnoclostridium, Parabacteroides, Prevotella_9, Roseburia, and Subdoligranulum were predominant among the two cohorts. On the basis of univariate analysis for overall microbiome variation, 18 matching variables exhibited significant association in both cohorts. A stepwise redundancy analysis revealed that there were four common covariates, Bristol Stool Scale (BSS) scores, gender, age, and defecation frequency, displaying non-redundant association with gut microbial variance. CONCLUSIONS: We conducted a comprehensive analysis of gut microbiota in healthy Japanese individuals, based on two independent cohorts, and obtained reliable evidence that questionnaire-based covariates such as frequency of bowel movement and specific dietary habit affects the microbial composition of the gut. To our knowledge, this was the first study to investigate integrated and non-redundant factors associated with gut microbiota among Japanese populations.

目的 ふん便(以下、便)は、我々の食事や栄養状態ならびに腸内細菌叢の特徴を反映し、身体の健康状態や栄養摂取状況を、簡便かつ非侵襲的に評価できるツールであると考えられる。一方で、便を包括的に評価し、簡便かつ客観的に評価する適切なツールに関する検討は十分に行われておらず、日常の排便状況や便性状を的確に把握できる有用な質問票が求められている。習慣的な排便状況(排便回数)や便性状(排便量、色、形状など)を把握するための評価ツールを作成し、排便日誌に基づく排便回数や便性状の記録と比較し内的妥当性を検討した。方法 22から78歳までの成人男女35人(45.2±17.1歳)を解析対象とした。習慣的な便に関する質問票(以下、習慣的便質問票)による最近1ヵ月間における平均的な排便回数、1回あたりの排便量、便の色や形状、便の浮きや腹部膨満感を調査した。この習慣的便質問票の各項目の再現性を検討するため、2回の調査を実施し、再現性を確認した。その後、排便日誌を用いて、毎日の排便時刻や便の性状などを1週間記録した。この排便日誌を基にした排便回数や便性状を内的妥当基準とし、習慣的便質問票により得られた回答を比較した。なお、習慣的便質問票における排便回数は、排便回数がカテゴリー化された回答を選択する選択回答法と数値による自由回答法の2種類で回答した。結果 習慣的便質問票の再現性を検討した結果、全ての項目においてスピアマン順位相関係数の有意な相関(ρ=0.431〜0.911)が認められ、重みづけκ係数においても高い一致度を示した(weighted κ=0.348〜0.841)。また、内的妥当性については、排便日誌による1週間あたりの排便回数と、習慣的便質問票における排便回数の回答を比較すると、自由回答法による1週間あたりの排便回数の方が、選択回答法より高い相関(ρ=0.855)を示した。さらに、便性状については、1週間の排便日誌における便性状の回答の中央値と習慣的便質問票での回答との相関を検討したところ、「便の浮き」を除いて有意な相関が示された(ρ=0.429〜0.800)。結論 本研究で作成した質問票は、習慣的な排便状況や便性状を評価する上で、再現性と内的妥当性が高いことが確認された。(著者抄録)

Previous studies have not investigated the determinants of resting oxidative stress, including physical fitness, as it relates to redox regulation. The present study therefore was aimed at identifying lifestyle and biological factors that determine resting oxidative stress, including objectively measured physical fitness. In 873 middle-aged and elderly men and women, age and anthropometric parameters, lifestyle-related parameters, medication and supplementation status, physical fitness, biochemical parameters, and nutritional intake status, as well as three plasma oxidative stress markers: protein carbonyl (PC), F2-isoprostane (F2-IsoP), and thiobarbituric acid reactive substances (TBARS), were surveyed and measured. The determinants of PC, F2-IsoP, and TBARS in all participants were investigated using stepwise multiple regression analysis. In PC, age (β=-0.11, P=0.002), leg extension power (β=-0.12, P=0.008), BMI (β=0.12, P=0.004), and HDL-C (β=0.08, P=0.040) were included in the regression model (adjusted R2=0.018). In the F2-IsoP, smoking status (β=0.07, P=0.060), BMI (β=0.07, P=0.054), and HbA1c (β=-0.06, P=0.089) were included in the regression model (adjusted R2=0.006). In TBARS, glucose (β=0.18, P<0.001), CRF (β=0.16, P<0.001), age (β=0.15, P<0.001), TG (β=0.11, P=0.001), antioxidant supplementation (β=0.10, P=0.002), and HbA1c (β=-0.13, P=0.004) were included in the regression model (adjusted R2=0.071). In conclusion, the present study showed that age, anthropometric index, lifestyle-related parameters, medication and supplementation status, objectively measured physical fitness, biochemical parameters, and nutritional intake status explain less than 10% of oxidative stress at rest.

The Tokyo 2020 Olympic Games is expected to be among the hottest Games in modern history, increasing the chances for exertional heat stroke (EHS) incidence, especially in non-acclimatised athletes/workers/spectators. The urgent need to recognise EHS symptoms to protect all attendees' health has considerably accelerated research examining the most effective cooling strategies and the development of wearable cooling technology and real-time temperature monitoring. While these technological advances will aid the early identification of EHS cases, there are several potential ethical considerations for governing bodies and sports organisers. For example, the impact of recently developed cooling wearables on health and performance is unknown. Concerning improving athletic performance in a hot environment, there is uncertainty about this technology's availability to all athletes. Furthermore, the real potential to obtain real-time core temperature data will oblige medical teams to make crucial decisions around their athletes continuing their competitions or withdraw. Therefore, the aim of this review is (1) to summarise the practical applications of the most novel cooling strategies/technologies for both safety (of athletes, spectators and workers) and performance purposes, and (2) to inform of the opportunities offered by recent technological developments for the early recognition and diagnosis of EHS. These opportunities are presented alongside several ethical dilemmas that require sports governing bodies to react by regulating the validity of recent technologies and their availability to all.

AIM: To re-evaluate the suitability of calf circumference as a surrogate marker of low muscle mass measured by both bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA). We also examined the effects of obesity and age on low muscle mass screening using calf circumference. METHODS: In total, 1239 adults participated in this cross-sectional study. We measured the maximum calf circumference in a standing position and appendicular skeletal muscle mass (ASM) using BIA and DXA. We defined low muscle mass based on the Asian Working Group for Sarcopenia 2019 consensus. RESULTS: Calf circumference was positively correlated with BIA-measured ASM/height2 (men: r = 0.81, women: r = 0.73) and DXA-measured ASM/height2 (men: r = 0.78, women: r = 0.76). In the subgroup analyses by obesity and age, calf circumference was also positively correlated with ASM/height2 . The optimal calf circumference cut-offs for low muscle mass screening measured by BIA and DXA were 35 cm (sensitivity 91%, specificity 84%) and 36 cm (sensitivity 82%, specificity 80%) for men, and 33 cm (sensitivity 82%, specificity 84%) and 34 cm (sensitivity 85%, specificity 72%) for women, respectively. CONCLUSIONS: Calf circumference is positively correlated with BIA- and DXA-measured muscle mass regardless of obesity and age and is a simple and accurate surrogate marker of muscle mass for diagnosing sarcopenia. Geriatr Gerontol Int 2020; 20: 943-950.

The relative contribution of diet to colorectal cancer (CRC) incidence is higher than that for other cancers. Animal models have revealed that Escherichia coli containing polyketide synthase (pks+ E. coli) in the gut participates in CRC development. The purpose of this cross-sectional study was to examine the relationship between dietary intake and the prevalence of pks+ E. coli isolated from the microbiota in faecal samples of 223 healthy Japanese individuals. Dietary intake was assessed using a previously validated brief-type self-administered diet history questionnaire. The prevalence of pks+ E. coli was evaluated using faecal samples collected from participants and specific primers that detected pks+ E. coli. The prevalence of pks+ E. coli was 26.9%. After adjusting for baseline confounders, the prevalence of pks+ E. coli was negatively associated with the intake of green tea (odds ratio [OR], 0.59 [95% confidence interval (CI) 0.30-0.88] per 100 g/1,000 kcal increment) and manganese (OR, 0.43 [95% CI 0.22-0.85] per 1 mg/1,000 kcal increment) and was positively associated with male sex (OR, 2.27 [95% CI 1.05-4.91]). While futher studies are needed to validate these findings, these results provide insight into potential dietary interventions for the prevention of CRC.

Rapid advances in technologies in the field of genomics such as high throughput DNA sequencing, big data processing by machine learning algorithms and gene-editing techniques are expected to make precision medicine and gene-therapy a greater reality. However, this development will raise many important new issues, including ethical, moral, social and privacy issues. The field of exercise genomics has also advanced by incorporating these innovative technologies. There is therefore an urgent need for guiding references for sport and exercise genomics to allow the necessary advancements in this field of sport and exercise medicine, while protecting athletes from any invasion of privacy and misuse of their genomic information. Here, we update a previous consensus and develop a guiding reference for sport and exercise genomics based on a SWOT (Strengths, Weaknesses, Opportunities and Threats) analysis. This SWOT analysis and the developed guiding reference highlight the need for scientists/clinicians to be well-versed in ethics and data protection policy to advance sport and exercise genomics without compromising the privacy of athletes and the efforts of international sports federations. Conducting research based on the present guiding reference will mitigate to a great extent the risks brought about by inappropriate use of genomic information and allow further development of sport and exercise genomics in accordance with best ethical standards and international data protection principles and policies. This guiding reference should regularly be updated on the basis of new information emerging from the area of sport and exercise medicine as well as from the developments and challenges in genomics of health and disease in general in order to best protect the athletes, patients and all other relevant stakeholders.

The relationships between cardiorespiratory fitness (CRF) measurements not confounded by adiposity and the prevalence of pre-diabetes mellitus (pre-DM) and diabetes mellitus (DM) are not well known. Thus, we aimed to investigate the associations of visceral fat (VF) and CRF with the prevalence of pre-DM/DM among Japanese adults. The study included 970 individuals (327 women and 643 men) who were 40-87 years old and had complete health examinations, abdominal fat area, and fitness data from WASEDA'S Health Study during 2015-2018. The VF area was measured using magnetic resonance imaging. CRF was measured using a cycle ergometer and was defined as VO2peak divided by fat free mass. The pre-DM/DM was identified based on the questionnaire and fasting blood tests. The odds ratios (ORs) and 95% confidence intervals (CIs) for prevalence of pre-DM/DM were calculated. Seventy-three participants had pre-DM and 48 participants had DM. Compared to the low VF group, the high VF group had a higher prevalence of pre-DM/DM (OR: 1.87, 95% CI: 1.18-2.96), although no significant relationship was observed between CRF and pre-DM/DM prevalence (P for trend = 0.239). The sub-group analyses also revealed no significant relationship between CRF and pre-DM/DM prevalence in the low VF group (P for trend = 0.979), although CRF values were inversely related to the prevalence of pre-DM/DM in the high VF group (P for trend = 0.024). Although CRF was not independently related to the prevalence of pre-DM/DM after adjusting for adiposity, higher VF values were related to a higher prevalence of pre-DM/DM. In addition, CRF levels were inversely associated with the prevalence of pre-DM/DM only among high VF individuals.

With an ever-increasing interest in understanding the relationships between the microbiota and the host, more tools to map, analyze and interpret these relationships have been developed. Most of these tools, however, focus on taxonomic profiling and comparative analysis among groups, with very few analytical tools designed to correlate microbiota and the host phenotypic data. We have developed a software program for creating a web-based integrative database and analysis platform called MANTA (Microbiota And pheNoType correlation Analysis platform). In addition to storing the data, MANTA is equipped with an intuitive user interface that can be used to correlate the microbial composition with phenotypic parameters. Using a case study, we demonstrated that MANTA was able to quickly identify the significant correlations between microbial abundances and phenotypes that are supported by previous studies. Moreover, MANTA enabled the users to quick access locally stored data that can help interpret microbiota-phenotype relations. MANTA is available at https://mizuguchilab.org/manta/ for download and the source code can be found at https://github.com/chenyian-nibio/manta.

This study examined the relationship between a healthy Japanese dietary pattern and micronutrient intake adequacy based on the Dietary Reference Intakes for Japanese 2015 (DRIs-J 2015) in men and women. A cross-sectional study was conducted in 1418 men and 795 women aged 40-87 years, who participated in the Waseda Alumni's Sports, Exercise, Daily Activity, Sedentariness, and Health Study. Dietary patterns were derived from principal component analysis of the consumption of 52 food and beverage items, which were assessed by a validated brief-type self-administered diet history questionnaire. Micronutrient intakes were quantified using the dietary reference intakes score (DRIs-score) for 21 micronutrients (based on DRIs-J 2015). The healthy dietary pattern score was significantly and positively correlated with the intakes of all 21 micronutrients used for constructing the DRIs-score in men and in women (each, p < 0.001). In both sexes, the healthy dietary pattern scores were strongly and positively associated with DRIs-scores (in men: ρ = 0.806, p < 0.001; in women: ρ = 0.868, p < 0.001), and the DRIs-scores reached a plateau around the highest tertile of the healthy dietary pattern score. These results indicate that a healthy Japanese dietary pattern is associated with adequate micronutrient intakes based on the DRIs-J 2015 in both men and women.

The question of why we age and finally die has been a central subject in the life, medical, and health sciences. Many aging theories have proposed biomarkers that are related to aging. However, they do not have sufficient power to predict the aging process and longevity. We here propose a new biomarker of human aging based on the mass-specific basal metabolic rate (msBMR). It is well known by the Harris-Benedict equation that the msBMR declines with age but varies among individual persons. We tried to renormalize the msBMR by primarily incorporating the body mass index into this equation. The renormalized msBMR (RmsBMR) which was derived in one cohort of American men (n = 25,425) was identified as one of the best biomarkers of aging, because it could well reproduce the observed respective American, Italian, and Japanese data on the mortality rate and survival curve. A recently observed plateau of the mortality rate in centenarians corresponded to the lowest value (threshold) of the RmsBMR, which stands for the final stage of human life. A universal decline of the RmsBMR with age was associated with the mitochondrial number decay, which was caused by a slight fluctuation of the dynamic fusion/fission system. This decay form was observed by the measurement in mice. Finally, the present approach explained the reason why the BMR in mammals is regulated by the empirical algometric scaling law.

Low serum 25-hydroxyvitamin D [25(OH)D] concentrations are associated with a high risk of insulin resistance and Type 2 diabetes mellitus in adults. However, it is unknown whether this is the case for American collegiate football and rugby football athletes. This study investigated the associations between serum 25(OH)D concentrations and glucose profiles in male collegiate football athletes. Thirty-four collegiate athletes (13 American football players and 21 rugby football players) aged 21 years were recruited. Their body fat percent and visceral fat area were measured by dual-energy X-ray absorptiometry and magnetic resonance imaging, respectively. The participants completed an oral glucose tolerance test (75 g glucose) with venous blood samples obtained at time points 0, 30, 60, 90, and 120 min for the determination of plasma glucose and serum insulin concentrations. Fasting serum 25(OH)D concentrations were also measured. The prevalence of vitamin D deficiency and insufficiency was 17.6% and 58.8%, respectively. The serum 25(OH)D concentrations were negatively associated with the increments in the areas under the curve (iAUC) for glucose (r = -.429, p = .011) and were borderline significantly correlated with the Matsuda index (r = -.303, p = .082). No relationships were observed between the serum 25(OH)D concentrations and other glucose profiles. Multiple stepwise regression analysis of glucose iAUC concentrations as the dependent variable indicated that the serum 25(OH)D concentrations, but not body fat indicators, were independently associated with glucose iAUC (β = -0.390, p = .025). The serum 25(OH)D concentrations were only an independent predictor for glucose iAUC in male collegiate football athletes, suggesting that increased 25(OH)D concentrations would be helpful for maintaining glucose homeostasis.

The benefit of training at altitude to enhance exercise performance remains equivocal although the most widely accepted approach is one where the athletes live and perform lower-intensity running at approximately 2300 m with high-intensity training at approximately 1250 m. The idea is that this method maintains maximal augmentations in total hemoglobin mass while reducing the performance impairment of high-intensity sessions performed at moderate altitude and thus preventing any detraining that can occur when athletes live and train at moderate altitude. This training regimen, however, is not universally accepted and some argue that the performance enhancement is due to placebo and training camp effects. Altitude training may affect an athlete's hematological parameters in ways similar to those observed following blood doping. Current methods of detection appear insufficient to differentiate between altitude training and blood doping making the interpretation of an athlete's biological passport difficult. Further research is required to determine the optimal method for altitude training and to enhance current detection methods to be able to differentiate better blood doping and altitude exposure.

Faecal volume, form, colour, and odour are associated with various diseases, dietary habits, and the gut microbiome. Multifaceted assessment of faecal condition will be needed for future research and practice. Faecal observation has advantages, as it is non-invasive, frequent, and easy. We have developed and validated an illustrative card tool for comprehensively faecal assessment. In 38 healthy adults, observations of volume, form, colour, and odour of faeces using the tool were compared to the objective characteristics of the actual faeces determined using a weighing scale, moisture meter, hardness meter, colourimeter, and odour measuring device. A significant positive correlation (ρ = 0.778) was observed between the number of faecal model (2 cm × 10 cm) units and the actual weight. The Bristol Stool Form Scale showed a significant positive correlation with the moisture content (ρ = 0.717) and negative correlations with faecal hardness (ρ = -0.843) and adhesiveness (ρ = -0.761). The L*a*b* colour space values of the stool differed significantly among observational judgments using the colour card tool. No significant correlation was observed between the observation of odour and the measured odour index. In conclusion, the faecal volume, form, and colour can be estimated by observation using the multifaceted assessment card tool.

OBJECTIVE: The aim of this study was to investigate the associations between dietary patterns and abdominal obesity among middle-aged and elderly Japanese people, using both waist circumference (WC) and visceral fat (VF) as indices. METHODS: A cross-sectional study was conducted with 829 adults (534 men and 295 women), 40 to 79 y of age, who participated in the Waseda Alumni's Sports, Exercise, Daily Activity, Sedentariness and Health Study (WASEDA'S Health Study). Dietary patterns were derived from principal component analysis. VF was measured using magnetic resonance imaging. To examine the associations of each dietary pattern with WC and VF, we calculated multivariate-adjusted means and 95% confidence intervals (CIs) of WC and VF for the tertile of each dietary pattern score. RESULTS: Two main dietary patterns were identified: "healthy Japanese" and "seafood and alcohol." The healthy Japanese dietary pattern score was inversely associated with WC and VF in men only. WC measurements were 84.9 cm (95% CI, 83.7-86.1), 83.9 cm (95% CI, 82.7-85.1), and 82.4 cm (95% CI, 81.2-83.6); Ptrend = 0.006, and VF measurements were 94.0 cm2 (95% CI, 85.6-102.4), 89.4 cm2 (95% CI, 81.1-97.7), and 80.4 cm2 (95% CI, 72.5-88.4); Ptrend = 0.027 for the lowest through the highest tertile of healthy Japanese dietary pattern scores in men. The seafood and alcohol dietary pattern was not associated with WC and VF. CONCLUSION: The healthy Japanese dietary pattern was negatively associated with WC and VF in middle-aged and elderly Japanese men.

The prevalence and incidence of type 2 diabetes mellitus (T2DM) have been increasing in both developed and developing countries. Although a modernization of lifestyles represented by westernized diets with high energy, fat, and sugar and low fiber intakes are some of the contributing factors to the T2DM epidemic, genetic factors are also important contributing factors to T2DM. Importantly, several T2DM-associated variants possibly interact with diet to influence T2DM risk. Furthermore, the human gut microbiome has emerged as a key determinant of T2DM development and plays roles in the success of dietary intervention and interpersonal variability in glycemic response to diet. There is considerable heterogeneity in the association of dietary intake with T2DM risk and glycemic traits, which may be partly explained by genetic factors and gut microbiome features. Understanding of the complex interaction among genetic factors, gut microbiome, and diet may contribute to the establishment of genomic information-based personalized nutrition to effectively prevent T2DM.

【目的】運動開始30〜45分前の糖質摂取は、運動開始直後に急激な血糖値の低下を生じさせる。一方、糖質摂取後に安静状態を保った場合に比べ、血糖値がどの程度低下するのかは明らかでない。本研究では、運動誘発性の血糖値の低下が、糖質摂取後に安静状態を保った場合に比べてどの程度であるのか、実際のスポーツ現場に近い状況である朝食摂取条件下にて検討した。【方法】男子大学生15名に対し、実験開始3時間前に朝食を摂取させた状態で、運動試行、安静試行の2試行を行わせた。運動試行では、150gの糖質を摂取してから30分間安静状態を保った後、最大酸素摂取量の75%の強度で60分間自転車運動を行った。安静試行では、糖質摂取後に90分間安静状態を維持した。それぞれの試行において採血を行い、血糖値を測定した。【結果】運動試行では、運動開始15分後に急激に血糖値が低下し、安静試行に比べて28±29mg/dl低い値を示した。また、安静試行から運動試行への血糖低下量が大きい被験者は、血糖低下量が小さい被験者に比べて、最大酸素摂取量が有意に高い値を示した。【結論】朝食摂取条件下においても、糖質摂取後に運動を行うことで、同量の糖質を摂取して安静状態を保った場合に比べて、約30mg/dl程度の血糖値の低下が生じることが明らかとなった。また、血糖低下量が大きい被験者では、最大酸素摂取量が高い傾向が認められた。(著者抄録)

BACKGROUND AND OBJECTIVES: The studies investigated the association between serum 25-hydroxyvitamin D (25(OH)D) concentrations and cardiorespiratory fitness (CRF) are few, and the results are controversial. We aim to evaluate the association of serum 25(OH)D concentrations with CRF in adults, and assess whether the associations vary with ageing. METHODS AND STUDY DESIGN: The study included 78 middle-aged (30-64 years) and 83 elderly (65-79 years) Japanese men. Hand grip strength and leg extension power were measured using hand grip and leg dynamometers, respectively. CRF was measured via a maximal graded exercise test and quantified as the peak oxygen uptake (VO2peak). Fasting serum 25(OH)D concentrations were determined by enzyme-linked immunosorbant assay. RESULTS: Serum 25(OH)D concentrations were positively related to hand grip strength (r=0.331, p<0.001), leg extension power (r=0.353, p<0.001), CRF (r=0.285, p<0.001) in all adults after adjustment for age. Significant interaction between 25(OH)D and age on CRF was observed (p<0.05). Age-related reduction of CRF was prevented in high 25(OH)D group (p<0.05). In the elderly, subjects in high 25(OH)D group had higher CRF compared with those in low group (p<0.05). CONCLUSIONS: We found that serum 25(OH)D concentrations significantly related with leg extension power, hand grip strength and CRF after adjustment for age. The relationship of vitamin D and CRF was affected by ageing. Higher serum 25(OH)D concentrations are a key predictor for CRF in the elderly, but not in middle-aged men.

INTRODUCTION: This study aimed to clarify whether 1 year of vitamin D3 supplementation has a direct effect on body composition and physical fitness in healthy adults. METHODS: Ninety-five participants randomly received either 420 IU vitamin D3 per day (n = 48) or placebo (n = 47) in a double-blind manner for 1 year. Lean body mass and percentage body fat were determined. Physical fitness including hand grip strength, leg extension power and cardiorespiratory fitness (CRF) were assessed. Serum 25-hydroxyvitamin D (25[OH]D) and 1,25-dihydroxyvitamin D (1,25[OH]2D) concentrations were assessed using ELISA kits. RESULTS: Serum 25(OH)D and (1,25[OH]2D) concentrations significantly increased by approximately 11.2 ± 9.2 ng/mL (pinteraction <0.001)and 7.0 ± 7.8 pg/mL (pinteraction <0.001) after 1 year of vitamin D3 supplementation respectively. Lean body mass significantly increased from 43.8 ± 9.6 to 44.3 ± 9.8 kg in vitamin D group, while no change was observed in placebo group (from 42.6 ± 8.9 to 42.4± 8.9 kg) after 1 year intervention. Furthermore, no treatment effects on other indicators of body composition and physical fitness were observed. CONCLUSIONS: One year of vitamin D supplementation effectively improves lean body mass, but not muscle strength and CRF in healthy adults.

PURPOSE: Carbohydrate (CHO) ingestion 30 to 45 min before exercise results in transient hypoglycemia after starting the exercise in some, but not all, subjects. However, whether transient hypoglycemia is more likely to occur under fed or fasted condition remains unknown. This study aimed to directly compare the effects of fasting versus feeding on plasma glucose responses after preexercise CHO intake and to examine the relationship between insulin responses and onset of transient hypoglycemia. METHODS: Sixteen subjects performed 60-min cycle ergometer exercises at 75% maximal oxygen uptake (V˙O2max) under overnight fasted and fed (4 h after breakfast) conditions. In both conditions, they consumed 500 mL of beverage (150 g of glucose) 30 min before beginning exercise. RESULTS: The mean plasma glucose concentrations 15 min after starting the exercise did not fall below 4.0 mmol·L (criteria for hypoglycemia) in both states; however, individual differences in the occurrence of transient hypoglycemia were noted. In the fasted state, plasma glucose levels transiently dropped below 4.0 mmol·L in five subjects, who had substantially higher serum insulin levels at the start of exercise, compared with those who did not develop hypoglycemia. Although seven subjects developed transient hypoglycemia in the fed state, no relationship was observed between insulin responses and hypoglycemia. Three subjects developed hypoglycemia in both fasted and fed states. CONCLUSIONS: These results suggest that transient hypoglycemia after preexercise CHO ingestion occurs in some, but not all, subjects, under both conditions. Furthermore, subjects with enhanced insulin responses seem to be more prone to transient hypoglycemia in the fasted condition.

Regular exercise reduces the risks for cardiovascular diseases. Although the gut microbiota has been associated with fitness level and cardiometabolic risk factors, the effects of exercise-induced gut microbiota changes in elderly individuals are unclear. This study evaluated whether endurance exercise modulates the gut microbiota in elderly subjects, and whether these changes are associated with host cardiometabolic phenotypes. In a randomized crossover trial, 33 elderly Japanese men participated in a 5-week endurance exercise program. 16S rRNA gene-based metagenomic analyses revealed that the effect of endurance exercise on gut microbiota diversity was not greater than interindividual differences, whereas changes in α-diversity indices during intervention were negatively correlated with changes in systolic and diastolic blood pressure, especially during exercise. Microbial composition analyses showed that the relative abundance of Clostridium difficile significantly decreased, whereas that of Oscillospira significantly increased during exercise as compared to the control period. The changes in these taxa were correlated with the changes in several cardiometabolic risk factors. The findings indicate that short-term endurance exercise has little effect on gut microbiota in elderly individuals, and that the changes in gut microbiota were associated with cardiometabolic risk factors, such as systolic and diastolic blood pressure, providing preliminary insight into the associations between the gut microbiota and cardiometabolic phenotypes.

Lower serum 25-hydroxyvitamin D (25(OH)D) concentrations are associated with more weight and fat mass gain in adults in the general population, but it is unknown whether this is the case in collegiate football athletes with greater body weight. This study aimed to investigate associations of serum 25(OH)D concentrations with body fat and ectopic fat accumulation, and to determine which fat indicators are closely related to serum 25(OH)D in male collegiate football athletes. Thirty-four collegiate athletes aged 21 years were recruited. Serum 25(OH)D concentrations and the levels of visceral fat area (VFA), vastus lateralis intramyocellular lipid (IMCL), extramyocellular lipid (EMCL), and intrahepatic lipid (IHCL) were measured. Serum 25(OH)D concentrations were negatively associated with the IHCL values (r = -0.372, p = 0.030), and the relationship remained after adjustment for several factors (r = -0.378, p = 0.047). Additionally, multiple stepwise regression analysis of IHCL content as the dependent variable indicated that 25(OH)D concentrations were a stronger predictor of IHCL content (β = -0.363, p = 0.030) than % body fat and VO₂peakFFM. Higher serum 25(OH)D concentrations are more closely related to lower IHCL content rather than any other fat indicators, suggesting that increasing serum 25(OH)D concentrations may have some effect that inhibits lipid accumulation in hepatic tissue, especially in heavy athletes.

Growth hormone (GH)/insulin-like growth factor-1 (IGF-1)/insulin signaling is one of the most plausible biological pathways regulating aging and longevity. Previous studies have demonstrated that several single nucleotide polymorphisms (SNPs) in the GH/IGF-1/insulin signaling-associated genes influence both longevity and adult height, suggesting the possibility of a shared genetic architecture between longevity and height. We therefore examined the relationship between 30 height-associated SNPs and extreme longevity in a Japanese population consisting of 428 centenarians and 4,026 younger controls. We confirmed that height-increasing genetic scores (HGSs) constructed based on 30 SNPs were significantly associated with height in the controls (p = 6.95 × 10-23). HGS was significantly and inversely associated with extreme longevity in women (p = .011), but not in men, although no SNPs were significantly associated with extreme longevity after Bonferroni correction. The odds ratio for extreme longevity in the lowest HGS group (≤27) and the second lowest HGS group (28-30) relative to the highest HGS group (≥37) was 1.71 (p = .056) and 1.69 (p = .034), respectively, for women. In conclusion, the present study demonstrated an inverse association between height-increasing alleles with extreme longevity in Japanese women, providing novel insight into the genetic architecture of longevity and aging.

We aimed to examine the effects of ingestion of different amounts of carbohydrate (CHO) after endurance exercise on neutrophil count, circulating cytokine levels, and the markers of neutrophil activation and muscle damage. Nine participants completed three separate experimental trials consisting of 1 h of cycling exercise at 70% V · O₂ max, followed by ingestion of 1.2 g CHO·kg body mass-1·h-1 (HCHO trial), 0.2 g CHO·kg body mass-1·h-1 (LCHO trial), or placebo (PLA trial) during the 2 h recovery phase in random order. Circulating glucose, insulin, and cytokine levels, blood cell counts, and the markers of neutrophil activation and muscle damage were measured. The concentrations of plasma glucose and serum insulin at 1 h after exercise were higher in the HCHO trial than in the LCHO and PLA trials. Although there were significant main effects of time on several variables, including neutrophil count, cytokine levels, and the markers of neutrophil activation and muscle damage, significant time × trial interactions were not observed for any variables. These results suggest that CHO ingestion after endurance exercise does not enhance exercise-induced increase in circulating neutrophil and cytokine levels and markers of neutrophil activation and muscle damage, regardless of the amount of CHO ingested.

BACKGROUND: Higher levels of physical activity and cardiorespiratory fitness are positively related to serum 25-hydroxyvitamin D [25(OH)D] concentrations; however, the response of 25(OH)D concentrations to chronic endurance exercise training is unclear. Therefore, the purpose of this study was to elucidate whether serum 25(OH)D concentrations were directly increased by 5 weeks of endurance exercise training and influenced by changes in body fat in elderly men. METHODS: Twenty elderly Japanese men were randomized to either the 5-week endurance exercise training group (ET group; N = 10) or the sedentary control group (SC group; N = 10). Fasting blood samples were collected to determine serum 25(OH)D and other blood parameters. The visceral fat area and hepatic fat content were assessed by magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively. RESULTS: After 5 weeks of endurance exercise training, the levels of maximal oxygen uptake (VO2 max) were significantly increased from 23.3 at baseline to 28.1 mL/kg/min at the endpoint for the ET group; levels were unchanged for the SC group. A significant seasonal reduction in serum 25(OH)D concentrations was observed in the SC group (P < 0.05), while no change was found in the ET group. The results may be partly attributed to the slight decrease in intrahepatic fat in the ET group. No changes were observed in percent body fat or visceral fat area. CONCLUSIONS: The results of our study suggest that 5 weeks of endurance training could inhibit the seasonal reduction in serum 25(OH)D concentrations without changes in body fat.

Context: Regular exercise or high physical activity levels are associated with higher serum 25-hydroxyvitamin D [25(OH)D] concentrations; however, the effect of acute exercise on serum 25(OH)D concentrations remains unclear. Objective: We aimed to clarify whether acute endurance exercise has a direct effect on the circulating 25(OH)D concentrations in young adults. Design and Setting: Exercise intervention trial in an institutional practice. Patients: Twenty young, active adults (males, n = 10; females, n = 10). Interventions: Participants were asked to perform a cycling exercise for 30 minutes at 70% maximal oxygen uptake. Main Outcome Measures: The serum concentrations of 25(OH)D and other blood parameters were assessed before exercise and at 0, 0.5, 1, 3, and 24 hours after exercise. Results: The serum 25(OH)D concentrations were significantly increased not only at 0 (P < 0.01), 1 (P < 0.05), and 3 hours (P < 0.01) after exercise, but they were also increased at 24 hours (P < 0.05) after acute endurance exercise in young adults. A significant sex × time interaction effect was observed (P < 0.05), and the incremental areas under the curve for the 25(OH)D concentrations were significantly higher in men than in the women (P < 0.01). Conclusions: There is a direct effect of endurance exercise on serum 25(OH)D concentrations. In addition, sex disparity was observed in the serum 25(OH)D response to acute endurance exercise, and the increase in 25(OH)D concentrations was greater in men than in women.

BACKGROUND/AIM: Alpha-kinase 2 (ALPK2), suggested to be a novel tumour-suppressor gene down-regulated by oncogenic KRAS, plays a pivotal role in luminal apoptosis in normal colonic crypts. The aim of this study was to determine the association between ALPK2 germline variants and colorectal cancer. MATERIALS AND METHODS: Missense single nucleotide variants in the exons of the ALPK2 gene in 2,343 consecutive autopsy cases (1,446 cases with cancer and 897 cases without cancer) were screened using HumanExome BeadChip arrays. To address the functional effect of a missense ALPK2 variant, a 3D floating cell culture was performed using HCT116-derived human colorectal cancer cells stably expressing wild-type (wt) ALPK2 (HCT116-wtALPK2) or amino acid-substituted (sub) ALPK2 (HCT116-subALPK2). RESULTS: We identified that one of the ALPK2 germline variants, rs55674018 (p.Q1853E), was significantly associated with the presence of cancer (adjusted odds ratio(OR)=4.39; 95% confidence interval(CI)=1.31-14.78, p=0.001). The p.Q1853E variant was present in the East Asian population and located in the immunoglobulin-like domain. Notably, the basolateral polarity of actin in the surface of HCT116-wtALPK2 spheroids was more attenuated compared to that of HCT116-subALPK2 spheroids. Furthermore, luminal apoptosis and cell aggregation were promoted by wtALPK2, but not by subALPK2 in 3D culture. CONCLUSION: The p.Q1853E variant of ALPK2, which had been accumulating in the Japanese population, induced a metastatic phenotype by disrupting ALPK2 function.

Metagenomic analysis based on the 16S rRNA gene is generally performed to examine the diversity and abundance of commensal bacteria in feces, which is now recognized to be associated with human health and diseases. Guanidine thiocyanate (GuSCN) solution is used as a less onerous way compared with a frozen method to transport and stock fecal samples at room temperature for DNA analysis; however, optimal methods to measure fecal bacterial composition in GuSCN solution remain to be investigated. Here, we examined the influence of various factors such as pretreatment (e.g., removing GuSCN solution and washing feces with phosphate-buffered saline (PBS) before mechanical lysis), fecal concentration in the GuSCN solution, storage time, and position of fecal subsampling on the 16S rRNA-based analysis of fecal bacteria in GuSCN solution. We found that pretreatment and fecal concentration affected the bacterial composition, and a little change was noted with subsampling position. Based on these results, we propose a basic protocol, including fecal sampling, sample storage, and DNA extraction, for the 16S rRNA-based analysis of bacterial composition in feces suspended in GuSCN solution.

Life span is a complex trait regulated by multiple genetic and environmental factors; however, the genetic determinants of extreme longevity have been largely unknown. To identify the functional coding variants associated with extreme longevity, we performed an exome-wide association study (EWAS) on a Japanese population by using an Illumina HumanExome Beadchip and a focused replication study on a Chinese population. The EWAS on two independent Japanese cohorts consisting of 530 nonagenarians/centenarians demonstrated that the G allele of CLEC3B missense variant p.S106G was associated with extreme longevity at the exome-wide level of significance (p = 2.33 x 10(-7), odds ratio [OR] = 1.50). The CLEC3B gene encodes tetranectin, a protein implicated in the mineralization process in osteogenesis as well as in the prognosis and metastasis of cancer. The replication study consisting of 448 Chinese nonagenarians/centenarians showed that the G allele of CLEC3B p. S106G was also associated with extreme longevity (p =.027, OR = 1.51), and the p value of this variant reached 1.87 x 10(-8) in the meta-analysis of Japanese and Chinese populations. In conclusion, the present study identified the CLEC3B p. S106G as a novel longevityassociated variant, raising the novel hypothesis that tetranectin, encoded by CLEC3B, plays a role in human longevity and aging.

The circadian clock regulates many physiological functions including physical activity and feeding patterns. In addition, scheduled exercise and feeding themselves can affect the circadian clock. The purpose of the present study was to investigate the relationship between physical/feeding activity and expression of clock genes in hair follicle cells in older adults. Twenty adult men (age, 68 ± 7 years, mean ± SE) were examined in this cross-sectional study. Prior to hair follicle cell collection, the participants were asked to wear a uniaxial accelerometer for one week. The timings of breakfast, lunch, and dinner were also recorded. Hair follicle cells were then collected over a 24 h period at 4 h intervals. The amplitude of PER3 expression was positively correlated with moderate and vigorous physical activity (r = 0.582, p = 0.007) and peak oxygen uptake (r = 0.481, p = 0.032), but these correlations were not observed for NR1D1 or NR1D2. No association was noted between meal times and the amplitude or the acrophase for any of these three clock genes. These findings suggest that rhythmic expression of the circadian clock gene PER3 is associated with the amount of daily physical activity and physical fitness in older adults.

BACKGROUND: Leukocyte cell-derived chemotaxin 2 (LECT2) is a hepatokine linking obesity to skeletal muscle insulin resistance. Although previous studies reported that obesity was associated with high levels of circulating LECT2 in human, the associations of detailed body fat distribution with LECT2 levels have not been examined. Furthermore, although animal study suggested that exercise decreased circulating LECT2 levels, it remains unknown whether physical fitness is associated with LECT2 levels in human. We therefore examined the relationship of plasma LECT2 levels with various adiposity indices and cardiorespiratory fitness (CRF) in middle-aged and elderly Japanese men. Furthermore, we examined the relationship of LECT2 levels with the presence of metabolic syndrome, hypertension, insulin resistance and dyslipidemia to determine the clinical significance of measuring circulating LECT2. MATERIALS AND METHODS: This was a cross-sectional study of 143 Japanese men (age: 30-79 years). Participants' plasma LECT2 levels were measured by an enzyme-linked immunosorbent assay. To assess their abdominal fat distributions, visceral fat area (VFA) and subcutaneous fat area (SFA) were measured using magnetic resonance imaging. CRF was assessed by measuring peak oxygen uptake ([Formula: see text]). RESULTS: All adiposity indices measured in this study were positively correlated with plasma LECT2 levels, while [Formula: see text] was negatively correlated with LECT2 levels after adjustment for age. The correlations, except for VFA were no longer significant with further adjustment for VFA. Stepwise multiple linear regression analysis revealed that VFA was the strongest predictor of plasma LECT2 levels. Plasma LECT2 levels differed based on the presence of metabolic syndrome and dyslipidemia, but not hypertension and insulin resistance. Logistic regression analyses revealed that plasma LECT2 levels were significantly associated with dyslipidemia independently of VFA; VFA was not significantly associated with dyslipidemia after adjustment for LECT2. CONCLUSION: VFA was the strongest predictor of plasma LECT2 that is a potential biomarker linking visceral obesity to dyslipidemia.

ObjectiveThe independent effects of acute endurance exercise on FGF21 metabolism are poorly understood. Therefore, the purpose of this study was to determine whether acute endurance exercise modulates serum postprandial FGF21 levels in an age-dependent manner.
DesignExercise intervention trial.
PatientsTwenty-eight subjects participated in the experiment, of whom 13 were excluded mainly because of a serum FGF21 level below the limit of detection. Thus, data from seven young (age: 18-22 years) and eight elderly male subjects (age: 62-69 years) were analysed.
MeasurementsParticipants were asked to perform a cycling exercise for 30 min at 70% maximal oxygen uptake, following carbohydrate intake. Blood samples were collected pre-exercise and 0 min, 30 min, 1 h, 3 h and 24 h after the cessation of exercise. Serum FGF21 levels were measured by an enzyme-linked immunosorbent assay.
ResultsHigher serum FGF21 was observed in the elderly subjects group throughout the experiment (P &lt; 005). There was no significant increase in serum FGF21 levels after the cessation of exercise, whereas serum FGF21 levels were significantly lower 24 h after the exercise compared with those pre-exercise, 0 min, 30 min and 1 h after the cessation of exercise in both groups (P &lt; 001). The response did not differ between the two groups because of no significant group x time interaction.
ConclusionsAcute endurance exercise lowers serum FGF21 levels 24 h following exercise. The results suggest that acute endurance exercise modulates postprandial FGF21 metabolism regardless of age.

目的 食事と健康との関連において食事パターンを用いた検討が行われているが、食事パターンを構成する複数の栄養素について、適正な量が摂取されているかを検討した報告は少ない。そこで、本研究では、主成分分析により中高年男性における代表的な食事パターンを同定し、各食事パターンと栄養素摂取量との関連を検討した。さらに、微量栄養素について、食事摂取基準(2010年版)で推奨されている指標を用いて複数の微量栄養素が適正量に摂取されているかを数値化して簡易的に評価し、食事パターンとの関連を検討することを目的とした。方法 40歳から79歳の中高年男性229人を対象として、簡易型自記式食事歴法質問票brief-type self-administered diet history questionnaire(BDHQ)による栄養調査を行った。52の食品および飲料の摂取量から主成分分析を行い、食事パターンを同定した。BDHQによって推定された微量栄養素のうち、食事摂取基準値が策定されている21種類の微量栄養素が適正量に摂取されているかを数値化して評価するためにDietary reference intakes score(DRIs-score)を作成した。各食事パターンにおいて複数の微量栄養素が適正量摂取されているかを検討するために、各食事パターンの主成分得点とDRIs-scoreにおいてSpearmanの順位相関係数を求めた。結果 主成分分析の結果、3つの食事パターンが同定された。第1食事パターンは野菜、果物、海草、きのこ、いも類が多く、ご飯(めし)が少ない「副菜型」、第2食事パターンはアルコールが多い「晩酌型」、第3食事パターンは果物・乳製品・菓子類が多い「間食型」とした。第1食事パターンの「副菜型」において、主成分得点とDRIs-scoreを構成するすべての微量栄養素との間に有意な相関関係が認められ、DRIs-scoreとの間には有意な正の相関関係(p=0.782、P&lt;0.001)が認められた。結論 第1食事パターンの「副菜型」の主成分得点は、日本人の食事摂取基準をもとに複数の微量栄養素の摂取が適正量であるかを評価したDRIs-scoreと相関し、第1食事パターンの重み付けが高い程、微量栄養素の栄養バランスが良好であることが示唆された。(著者抄録)

A genetic risk score (GRS) was developed for predicting fracture risk based on lifetime prevalence of femoral fractures in 924 consecutive autopsies of Japanese males. A total of 922 non-synonymous single nucleotide polymorphisms (SNPs) located in 62 osteoporosis susceptibility genes were genotyped and evaluated for their association with the prevalence of femoral fracture in autopsy cases. GRS values were calculated as the sum of risk allele counts (unweighted GRS) or the sum of weighted scores estimated from logistic regression coefficients (weighted GRS). Five SNPs (alpha-EY-iduronidase rs3755955, C7orf58 rs190543052, homeobox C4 rs75256744, G patch domain-containing gene 1 rs2287679, and Werner syndrome rs2230009) showed a significant association (P &lt; 0.05) with the prevalence of femoral fracture in 924 male subjects. Both the unweighted and weighted GRS adequately predicted fracture prevalence; areas under receiver-operating characteristic curves were 0.750 [95 % confidence interval (CI) 0.660-0.840] and 0.770 (95 % CI 0.681-0.859), respectively. Multiple logistic regression analysis revealed that the odds ratio (OR) for the association between fracture prevalence and unweighted GRS aeyen3 (n = 124) was 8.39 (95 % CI 4.22-16.69, P &lt; 0.001) relative to a score &lt; 3 (n = 797). Likewise, the OR for a weighted GRS of 6-15 (n = 135) was 7.73 (95 % CI 3.89-15.36, P &lt; 0.001) relative to scores of 0-5 (n = 786). The GRS based on risk allele profiles of the five SNPs could help identify at-risk individuals and enable implementation of preventive measures for femoral fracture.

Higher circulating 25-hydroxyvitamin D (25[OH]D) concentration has been linked to a lower prevalence of insulin resistance and type 2 diabetes mellitus. However, randomized controlled trials have not clarified the effect of vitamin D supplementation on insulin resistance in healthy adults. The objective of this study was to assess the effect of vitamin D supplementation for 1 year on insulin resistance; the study was a secondary analysis of a clinical trial. We hypothesized that increased 25(OH)D concentration after vitamin D supplementation for 1 year would significantly improve insulin resistance. Ninety-six healthy adults participated in this study, of whom 81 completed the study. The participants randomly received daily either 420 IU vitamin D3 or placebo in a double-blind manner for 1 year. The levels of fasting insulin, glucose, and other parameters were assessed at baseline and after 1 year of intervention. Homeostasis model assessment of insulin resistance index was calculated from insulin and glucose levels. Visceral fat area and physical activity were also investigated. Serum 25(OH)D and 1,25-dihydroxyvitamin D concentrations were significantly increased by approximately 29.5 nmol/L and 7.0 pg/mL, respectively, after 1-year vitamin D supplementation. After vitamin D supplementation, fasting glucose levels and values of homeostasis model assessment of insulin resistance index significantly decreased from 88.3 to 85.3 mg/dL (P &lt; .01) and 1.17 to 0.84 (P &lt; .01), respectively, and the results were independent of physical activity and visceral fat accumulation. In conclusion, the present study showed that vitamin D supplementation for 1 year effectively improves fasting glucose level and insulin resistance in healthy Japanese adults. (C) 2016 Elsevier Inc. All rights reserved.

Objectives Dietary patterns are studied to determine the relationship between diet and health. However, little is known about whether various dietary patterns fulfill adequate nutrient intake. Therefore, the purpose of this study was to investigate the association between major dietary patterns and nutritional intakes in middle-aged and elderly men. Furthermore, we examined the associations between dietary patterns and micronutrients status by using the reference values from the Dietary Reference Intakes for Japanese 2010 (DRIs-J 2010).Methods A total of 229 middle-aged and elderly men (age range, 40-79 years) participated in this study. The dietary patterns were determined using principal component analysis of 52 food and beverage items via a validated brief diet history questionnaire. Overall, micronutrient intake status was quantified using a dietary reference intakes score (DRIs-score) for 21 micronutrients (based on the DRIs-J 2010). The association of the nutrient intake and the DRIs-score with each factor score was evaluated using Spearman's correlation coefficient.Results Three dietary patterns were identified: "side dish", "evening drink", and "snack". The "side dish" pattern was characterized by a high intake of vegetables, fruits, seaweeds, mushrooms, and potatoes, and low intake of rice. Spearman's correlation showed that the "side dish" pattern correlated with each of the 21 micronutrients, and positively correlated with the DRIs-score (ρ=0.782, P<0.001).Conclusions The "side dish" pattern was positively related with the DRIs-score, calculated from the DRIs-J 2010. The result suggested the "side dish" pattern may provide a favorable nutrient balance in middle-aged and elderly men.

Cardiometabolic diseases such as type 2 diabetes mellitus, stroke, and coronary heart disease are complex disorders influenced by multiple genetic and environmental factors. Physical activity is one of the most reliable predictors of cardiometabolic diseases among various lifestyle factors. Numerous epidemiological studies have revealed that higher levels of physical activity and cardiorespiratory fitness are strongly associated with a lower incidence of cardiometabolic diseases and all-cause mortality in various populations. On the other hand, genetic factors also contribute to susceptibility to cardiometabolic diseases. Familial and twin studies have demonstrated that the strength of the contribution of genetic factors to cardiometabolic diseases is comparable to that of environmental factors, and a large number of genetic variants associated with cardiometabolic diseases have been identified. Importantly, genetic factors explain the heterogeneity of the effect that regular exercise has on the improvement of cardiometabolic risk, and there is evidence that regular exercise possibly attenuates the genetic predisposition to cardiometabolic diseases. Thus, genetic factors and exercise interact with each other to determine susceptibility to cardiometabolic diseases. This article reviews recent studies exploring genetic factors that determine susceptibility to cardiometabolic diseases, with an emphasis on the studies examining the gene-exercise interactions in cardiometabolic risk.

Context: Age-related hepatic fat accumulation increases the risk of cardiometabolic diseases, and the fibroblast growth factor (FGF) 21-resistant state caused by fatty liver underlies the pathogenesis of these diseases.
Objective: Previous studies suggested that a higher level of cardiorespiratory fitness was associated with both lower hepatic fat content and serum FGF21 levels; however, the effect of endurance exercise on hepatic fat content and serum FGF21 concentration has not been studied. Therefore, we aimed to elucidate whether endurance exercise reduced hepatic fat content and serum FGF21 levels.
Design: This is a randomized crossover trial.
Setting: The study setting was an institutional practice.
Patients: Thirty-three elderly Japanese men participated in the study.
Intervention: The intervention was a 5-week endurance exercise program comprising three cycle ergometer sessions per week.
Main Outcome Measures: Hepatic fat content was assessed by proton magnetic resonance spectroscopy, and serum FGF21 level was determined by ELISA.
Results: A5-week endurance exercise program decreased the hepatic fat content and serum FGF21 levels without weight loss, and the changes were higher in the exercise period than in the control period (P = .021 and P = .026, respectively). Correlation analysis demonstrated that only the change in hepatic fat content was significantly and positively correlated with change in serum FGF21 levels (r = 0.366, P = .006).
Conclusions: A 5-week endurance exercise program decreased hepatic fat content and serum FGF21 levels without weight loss in elderly men, and exercise-induced hepatic fat reduction mediated the reduction in serum FGF21 levels. These findings suggest that endurance exercise modulates hepatic fat content and FGF21 resistance, regardless of obesity status.

BACKGROUND: Many genetic and environmental factors are involved in the etiology of nicotine dependence. Although several candidate gene variations have been reported by candidate gene studies or genome-wide association studies (GWASs) to be associated with smoking behavior and the vulnerability to nicotine dependence, such studies have been mostly conducted with subjects with European ancestry. However, genetic factors have rarely been investigated for the Japanese population as GWASs. To elucidate genetic factors involved in nicotine dependence in Japanese, the present study comprehensively explored genetic contributors to nicotine dependence by using whole-genome genotyping arrays with more than 200,000 markers in Japanese subjects. RESULTS: The subjects for the GWAS and replication study were 148 and 374 patients, respectively. A two-stage GWAS was conducted using the Fagerström Test for Nicotine Dependence (FTND), Tobacco Dependence Screener (TDS), and number of cigarettes smoked per day (CPD) as indices of nicotine dependence. For the additional association analyses, patients who underwent major abdominal surgery, patients with methamphetamine dependence/psychosis, and healthy subjects with schizotypal personality trait data were recruited. Autopsy specimens with various diseases were also evaluated. After the study of associations between more than 200,000 marker single-nucleotide polymorphisms (SNPs) and the FTND, TDS, and CPD, the nonsynonymous rs2653349 SNP (located on the gene that encodes orexin [hypocretin] receptor 2) was selected as the most notable SNP associated with FTND, with a p value of 0.0005921 in the two-stage GWAS. This possible association was replicated for the remaining 374 samples. This SNP was also associated with postoperative pain, the initiation of methamphetamine use, schizotypal personality traits, and susceptibility to goiter. CONCLUSIONS: Although the p value did not reach a conventional genome-wide level of significance in our two-stage GWAS, we obtained significant results in the subsequent analyses that suggest that the rs2653349 SNP (Val308Ile) could be a genetic factor that is related to nicotine dependence and possibly pain, schizotypal personality traits, and goiter in the Japanese population.

Aim: This study aimed to examine whether cardiorespiratory fitness (CRF) is associated with arterial stiffening, evaluated using the cardio-ankle vascular index (CAVI), independent of visceral fat (VF) in middle-aged and elderly Japanese men. We also examined whether the relationship between CRF and the CAVI is modified by age and/or hypertension.
Methods: The CAVI was determined in 157 Japanese men (age range, 30-79 years), including 96 hypertensive subjects (61.1%). CRF was assessed by measuring the peak oxygen uptake (VO(2)peak). The subjects were divided into low- and high-CRF groups, and the VF area was assessed using magnetic resonance imaging.
Results: The VO(2)peak correlated with the CAVI following adjustment for age and body mass index in the middle-aged and elderly groups (all the subjects: r = -0.285, p&lt;0.001; middle-aged: r = -0.240, p = 0.040; elderly: r = -0.225, p = 0.049). VF also correlated with the CAVI (r = 0.230, p = 0.004). A multiple linear regression analysis revealed that age (beta = 0.406, p&lt;0.001) and the VO(2)peak (beta = -0.186, p = 0.015) were associated with the CAVI independently of VF and the mean blood pressure. Two-way ANCOVA adjusted for age demonstrated that the hypertensive individuals had higher CAVI values than the normotensive individuals in the low-CRF group, whereas no significant differences in the CAVI were observed in the high-CRF group (p for interaction &lt;0.05).
Conclusions: In the present study, CRF was found to be associated with the CAVI, independent of age and VF, in hypertensive middle-aged and elderly Japanese men.

Aim: Low circulating 25-hydroxyvitamin D [25(OH) D] concentration has been linked to a high prevalence of cardiovascular disease. One explanation for this phenomenon is that there is an association between the serum 25(OH) D level and lipid profiles. However, studies examining this relationship are limited and have yielded inconsistent results. We thus aimed to evaluate the association between the serum 25(OH) D concentration and lipid profiles in Japanese men taking into consideration confounding factors, including the visceral fat area (VFA) and cardiorespiratory fitness.
Methods: A total of 136 men (age range: 20-79 years) participated in our study. Fasting blood samples were analyzed to determine the 25(OH) D, oxidized low-density lipoprotein (oxLDL), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein (Apo) A-1 and ApoB levels. The VFA was evaluated on magnetic resonance imaging (MRI), and cardiorespiratory fitness was assessed by measuring the peak oxygen uptake (VO2 peak).
Results: The median 25(OH) D concentration was 35.6 nmol/L, and the prevalence of 25(OH) D deficiency was 78.7%. A multiple linear regression analysis revealed that the serum 25(OH)D concentration was inversely related to the LDL-C/HDL-C, TG, ApoB and ApoB/ApoA-1 values, even after adjusting for age, season, smoking status, alcohol consumption, medication use, vitamin D intake, calcium intake, VFA and cardiorespiratory fitness.
Conclusions: Serum 25(OH) D level is inversely correlated with the LDL-C/HDL-C, TG, ApoB and ApoB/ApoA-1 values in Japanese men, independent of the VFA and cardiorespiratory fitness.

Here, we aim to investigate the independent and combined associations of serum 25-hydroxyvitamin D (25(OH)D) and cardiorespiratory fitness (CRF) with glucose metabolism. Fasting blood samples of 107 men aged 40-79 years were analyzed for 25(OH) D, glucose, insulin, glycated hemoglobin, and lipid profile. Homeostasis model assessment of insulin resistance index (HOMA-IR) was calculated from the fasting concentrations of glucose and insulin. Visceral fat area (VFA) was determined by magnetic resonance imaging and CRF by measuring maximal oxygen uptake. Median 25(OH) D concentration was 36.3 nmol/L, while the prevalence of 25(OH)D deficiency was 74.8%. Participants with high CRF had significantly lower HOMA-IR, glycated hemoglobin, and insulin values than participants with low CRF (p &lt; 0.05). Higher 25(OH) D concentration was strongly correlated with lower HOMA-IR and insulin values independent of VFA (p &lt; 0.01) but significantly affected by CRF. In the high CRF group, participants with higher 25(OH) D concentration had lower HOMA-IR values than participants with low 25(OH) D concentration (p &lt; 0.05). Higher 25(OH) D and CRF are crucial for reducing insulin resistance regardless of abdominal fat. In addition, higher 25(OH) D concentration may strengthen the effect of CRF on reducing insulin resistance in middle-aged and elderly Japanese men with high CRF.

Context: Fibroblast growth factor-21 (FGF21) is an important metabolic regulator suggested to improve glucose metabolism and prevent dyslipidemia. An FGF21-resistant state that increases circulating FGF21 has been reported in obese patients. Although regular exercise prevents metabolic disease, the relationship of the fitness level to serum FGF21 level and body fat distribution in humans remains poorly understood.
Objective: The objective of the study was to determine the relationship among the serum FGF21 concentration, cardiorespiratory fitness (CRF) level, and visceral fat area (VFA).
Design: Serum FGF21 was measured by an ELISA in 166 middle-aged and elderly Japanese men (aged 30-79 y) and 25 untrained and 21 endurance-trained young men (aged 19-29 y). CRF was assessed by measuring the peak oxygen uptake (VO(2)peak) and VFA by magnetic resonance imaging.
Results: In the middle-aged and elderly subjects, the serum FGF21 level correlated with the VO(2)peak (r = -0.355, P &lt; .001) and VFA (r = 0.487, P &lt; .001). Stepwise multiple regression analysis showed VFA to be most strongly associated with the serum FGF21 level (beta = .360, P &lt; .001), and VO(2)peak was also an independent predictor of the serum FGF21 level (beta = -.174, P = .019). Furthermore, the proportion of subjects with an FGF21 level below the limit of detection was significantly higher among the endurance-trained than among the untrained young men (71.4% vs 24.0%, P = .001), and the VO2 peak and VFA were independently associated with an undetectable FGF21 level (P &lt; .05).
Conclusions: CRF and VFA are key determinants of the circulating FGF21 concentration.

Genome-wide association studies identified single nucleotide polymorphisms (SNPs) associated with body mass index (BMI) in middle-aged populations; however, it is unclear whether these SNPs are associated with body fatness in elderly people. We examined the association between genetic risk score (GRS) from BMI-associated SNPs and body fatness in elderly Japanese men. We also examined the contribution of GRS, dietary macronutrient intake, and physical activity to body fatness by different age groups. GRS was calculated from 10 BMI-associated SNPs in 84 middle-aged (30-64 years) and 97 elderly (65-79 years) Japanese men; subjects were divided into low, middle, and high GRS groups. Dietary macronutrient intake was assessed using a questionnaire, and physical activity was evaluated using both a questionnaire and an accelerometer. The middle-aged individuals with a high GRS had greater BMI; waist circumference; and total abdominal fat, visceral fat, and subcutaneous fat areas than the middle-aged individuals with low GRS, whereas the indicators were not different between the GRS groups in elderly individuals. Multiple linear regression analysis showed that GRS was the strongest predictor of BMI, total abdominal fat, and visceral fat in the middle-aged group, whereas fat, alcohol, and protein intakes or vigorous-intensity physical activity were more strongly associated with these indicators than was GRS in the elderly group. These results suggest that GRS from BMI-associated SNPs is not predictive of body fatness in elderly Japanese men. The stronger contribution of dietary macronutrient intake and physical activity to body fatness may attenuate the genetic predisposition in elderly men.

High cardiorespiratory fitness (CRF) is associated with a reduced risk of Type 2 diabetes mellitus (T2DM) and improved beta-cell function; genetic factors also determine these risks. This cross-sectional study investigated whether CRF modifies the association of polygenic risk of T2DM with glucose metabolism in nondiabetic Japanese men. Fasting plasma glucose, insulin, and glycated hemoglobin (HbA1c) levels were measured in 174 Japanese men (age: 20-79 yr). beta-Cell function and insulin resistance were evaluated by calculating HOMA-beta and HOMA-IR, respectively. CRF was assessed by measuring maximal oxygen uptake ((V) over dot(O2max)). Subjects were divided into the low and high CRF groups within each age group according to the median (V) over dot(O2max). Eleven single nucleotide polymorphisms (SNPs) associated with T2DM were analyzed and used to calculate genetic risk score (GRS); subjects were divided into the low, middle, and high GRS groups. The high GRS group had higher HbA1c levels than the low GRS group in both the low and high CRF groups (P &lt; 0.05). Furthermore, the individuals with a high GRS had a lower HOMA-beta than those with a low GRS regardless of CRF (P &lt; 0.05). In multiple linear regression analysis, although GRS was a significant predictor of HbA1c (beta = 0.153, P = 0.025), (V) over dot(O2max) was also associated with HbA1c (beta = -0.240, P = 0.041) independent of GRS. These results suggest that CRF is associated with HbA1c levels independent of GRS derived from T2DM-related SNPs; however, it does not modify the association of GRS with increased HbA1c or impaired beta-cell function.

Objective. This cross-sectional study analyzed the association of serum irisin concentrations with cardiorespiratory fitness levels and common single nucleotide polymorphisms (SNPs) in the FNDC5 gene and examined the relationships between cardiorespiratory fitness levels, common SNPs in FNDC5, and glucose metabolism.
Materials/Methods. Cardiorespiratory fitness was assessed by measuring peak oxygen uptake (VO(2)peak) and serum irisin levels by ELISA in 163 Japanese men (age, 21-79 years). Subjects were divided into low- and high-fitness groups within each age group according to the median VO(2)peak value. Common SNPs (rs3480 and rs16835198) of the FNDC5 gene were genotyped with the TaqMan assay. Glucose metabolism was evaluated by measuring HbA1c, fasting plasma glucose (FPG), insulin levels, and HOMA-IR.
Results. Serum irisin levels were negatively correlated with age (p &lt;0.001) and not associated with the VO(2)peak or HOMA-IR. In the low-fitness group, SNP analysis revealed that subjects with the rs3480 AG and GG genotypes had higher levels of insulin and HOMA-IR than those with the AA genotype (p &lt;0.01; no significant difference was observed in the high-fitness group). The GG genotypes of rs16835198 were associated with increased HbA1c and FPG in the low-fitness group only (p &lt;0.05). SNPs and both fitness groups were not associated with serum irisin levels.
Conclusions. In Japanese men, cardiorespiratory fitness levels and common SNPs in FNDC5 are not associated with circulating irisin levels, whereas high cardiorespiratory fitness abolishes the association between the rs3480 and rs16835198 SNPs and glucose metabolism independent of serum irisin levels. (C) 2014 Elsevier Inc. All rights reserved.

High cardiorespiratory fitness (CRF) is associated with a reduced risk for dyslipidemia; however, blood lipid levels are also affected by individual genetic variations. We performed a cross-sectional study to determine whether CRF modifies polygenic risk for dyslipidemia. Serum levels of triglycerides (TG), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C) were measured in 170 Japanese men (age 20-79 yr). CRF was assessed by measuring maximal oxygen uptake ((V) over dot O-2max), and subjects were divided into low-fitness and high-fitness groups according to the reference (V) over dot O-2max value for health promotion in Japan. We analyzed 19 single nucleotide polymorphisms (SNPs) associated with TG, LDL-C, or HDL-C levels. Based on these SNPs, we calculated three genetic risk scores (GRSs: TG-GRS, LDL-GRS, and HDL-GRS), and subjects were divided into low, middle, and high groups according to the tertile for each GRS. Serum TG levels of low-fitness individuals were higher in the high and middle TG-GRS groups than in the low TG-GRS group (P &lt; 0.01 and P &lt; 0.05, respectively), whereas no differences were detected in the TG levels of high-fitness individuals among the TG-GRS groups. In contrast, the high LDL-GRS group had higher LDL-C levels than did the low LDL-GRS group, and HDL-C levels were lower in the high HDL-GRS group than in the low HDL-GRS group regardless of the fitness level (P &lt; 0.05). These results suggest that high CRF attenuates polygenic risk for hypertriglyceridemia; however, high CRF may not modify the polygenic risk associated with high LDL-C and low HDL-C levels in Japanese men.

Background: Senescence-accelerated mice (SAM) are a series of mouse strains originally derived from unexpected crosses between AKR/J and unknown mice, from which phenotypically distinct senescence-prone (SAMP) and -resistant (SAMR) inbred strains were subsequently established. Although SAMP strains have been widely used for aging research focusing on their short life spans and various age-related phenotypes, such as immune dysfunction, osteoporosis, and brain atrophy, the responsible gene mutations have not yet been fully elucidated.
Results: To identify mutations specific to SAMP strains, we performed whole exome sequencing of 6 SAMP and 3 SAMR strains. This analysis revealed 32,019 to 38,925 single-nucleotide variants in the coding region of each SAM strain. We detected Ogg1 p.R304W and Mbd4 p.D129N deleterious mutations in all 6 of the SAMP strains but not in the SAMR or AKR/J strains. Moreover, we extracted 31 SAMP-specific novel deleterious mutations. In all SAMP strains except SAMP8, we detected a p.R473W missense mutation in the Ldb3 gene, which has been associated with myofibrillar myopathy. In 3 SAMP strains (SAMP3, SAMP10, and SAMP11), we identified a p.R167C missense mutation in the Prx gene, in which mutations causing hereditary motor and sensory neuropathy (Dejerine-Sottas syndrome) have been identified. In SAMP6 we detected a p.S540fs frame-shift mutation in the Il4ra gene, a mutation potentially causative of ulcerative colitis and osteoporosis.
Conclusions: Our data indicate that different combinations of mutations in disease-causing genes may be responsible for the various phenotypes of SAMP strains.