Hirofumi Zempo

Objectively measured light-intensity lifestyle activity and sedentary time are independently associated with metabolic syndrome: a cross-sectional study of Japanese adults

BackgroundReducing sedentary time and increasing lifestyle activities, including light-intensity activity, may be an option to help prevent metabolic syndrome (MetS). The purpose of the present study was to examine whether objectively measured light-intensity lifestyle activity and sedentary time is associated with MetS, independent of moderate–vigorous intensity physical activity (MVPA).MethodsThe participants in this cross-sectional study were 483 middle-aged Japanese adults, aged 30–64xa0years. The participants were divided into those with or without MetS according to the Japanese criteria for MetS. A triaxial accelerometer was used to measure light-intensity lifestyle activity [1.6–2.9 metabolic equivalents (METs)] and sedentary time (≤1.5 METs). Logistic regression was used to predict MetS from the levels of light-intensity lifestyle activity and sedentary time with age, sex, smoking, calorie intake, accelerometer wear time, and MVPA as covariates.ResultsThe odds ratios (OR) for MetS in the highest and middle tertiles of light-intensity lifestyle activity were 0.44 [95% confidence interval (CI): 0.24 to 0.81] and 0.51 (95% CI: 0.29 to 0.89) relative to the lowest tertile, after adjustment for age, sex, smoking, calorie intake, accelerometer wear time and MVPA (Ptrendu2009=u20090.012). Sedentary time was also associated with the risk of MetS (Ptrendu2009=u20090.018). Among participants in the highest tertile of sedentary time, the risk of MetS was 2.27-times greater than that in the lowest tertile (95% CI: 1.25 to 4.11). The risk of MetS was not significantly increased in subjects in the middle tertile of sedentary time.ConclusionsWe found that light-intensity lifestyle activity and sedentary time were significantly associated with the risk of MetS, independent of MVPA. The results of our study suggest that public health messages and guidelines should be refined to include increases in light-intensity lifestyle activity and/or decreases in sedentary time, alongside promoting MVPA, to prevent MetS.

Association between physical activity and metabolic syndrome in middle-aged Japanese: a cross-sectional study.

BackgroundAlthough many studies have reported an association between self-reported physical activity and metabolic syndrome (MetS), there is limited information on the optimal level of physical activity required to prevent MetS. This study aimed to determine the association between objectively measured physical activity and MetS in middle-aged Japanese individuals. We also determined the optimal cutoff value for physical activity required to decrease the risk of developing MetS.MethodsA total of 179 men and 304 women, aged between 30 and 64 years, participated in this study. Participants were divided into two groups using the Japanese criteria for MetS as those with MetS or pre-MetS, and those without MetS. Participants were considered to be physically active if they achieved a physical activity level of 23 metabolic equivalents (METs) h/week, measured using a triaxial accelerometer. The association between physical activity and MetS was analyzed using logistic regression with the following covariates: sex, age, sedentary time, low intensity activity, calorie intake, smoking, menopause and body mass index. We also evaluated the factors that determined the association between the prevalence of MetS and pre-MetS and the physical activity cutoff value using classification and regression tree (CART) analysis.ResultsThe odds ratio for MetS and pre-MetS was 2.20 for physically inactive participants (< 23 METs h/week), compared with physically active participants (≥ 23 METs h/week). The corresponding odds ratios for men and women were 2.27 (P < 0.01) and 1.95 (not significant), respectively. CART analyses revealed that moderate-vigorous physical activity of > 26.5 METs h/week was sufficient to decrease the prevalence of MetS and pre-MetS in middle-aged Japanese men and women.ConclusionsThe results of this cross-sectional study indicate that the Exercise and Physical Activity Reference for Health Promotion 2006 is inversely associated with the prevalence of MetS in men. Our results also suggest that moderate physical activity of > 26.5 METs h/week may decrease the risk of developing MetS and pre-MetS in middle-aged Japanese individuals.

ACTN3 polymorphism affects thigh muscle area.

Muscle mass is an important factor influencing the activity of daily living in older adults. We aimed to investigate whether alpha-actinin-3 (ACTN3) gene R577X polymorphism affects muscle mass in older Japanese women. A total of 109 women (mean+/-SD, 64.1+/-6.0 years) were genotyped for the R/X variant of ACTN3. Mid-thigh muscle cross-sectional area (CSA) was assessed using MRI and compared using analysis of covariance models adjusted for body weight. In addition, physical activity and protein intake were measured as the living environmental factors affecting muscle mass. The ACTN3 R577X genotype distributions of the subjects were 19, 63 and 27 for the RR, RX, and XX genotypes, respectively. No differences in physical activity and protein intake were observed among the genotypes. The XX genotype showed lower thigh muscle CSA compared with RR&RX genotype (mean+/-SEM; XX: 69.1+/-1.8 cm(2), RR&RX: 73.6+/-1.1 cm(2); p<0.05). The results of the present study suggest that ACTN3 R577X polymorphism influences muscle mass in older Japanese women.

Combination of polymorphisms in the β2-adrenergic receptor and nitric oxide synthase 3 genes increases the risk for hypertension

Objective Hypertension is a major risk factor for cardiovascular disease. Polymorphism in the β2-adrenergic receptor (ADRB2) and nitric oxide synthase 3 (NOS3) genes is associated with clinical cardiovascular phenotypes. The Arg16Gly and Glu298Asp polymorphisms of ADRB2 and NOS3 genes, respectively, have been reported to be associated with hypertension. We hypothesized that a combination of these two polymorphisms increases the risk for hypertension. Hence, we examined the effect of this combination of single-nucleotide polymorphisms on the risk for hypertension. Methods Our cross-sectional study comprised 402 middle-aged and elderly human participants. We determined the genotypes of Arg16Gly and Glu298Asp single-nucleotide polymorphisms in ADRB2 and NOS3, respectively, by TaqMan PCR method; we also measured the resting blood pressure. Results The odds ratio for the presence of hypertension in individuals having the Gly/Gly genotype of ADRB2 compared with those having the other genotypes (Arg/Arg and Arg/Gly) was 2.87. With regard to the Glu298Asp polymorphism in NOS3, the odds ratio for the presence of hypertension in individuals having the Glu/Glu genotype of NOS3 when compared with those having the other genotypes (Asp/Asp and Asp/Glu) was 2.79. Interestingly, the odds ratio was 7.64 for individuals having a combination of the Gly/Gly genotype of ADRB2 and Glu/Glu genotype of NOS3 when compared with those having a combination of Arg/Arg and Arg/Gly genotypes of ADRB2 and Asp/Asp and Asp/Glu genotypes of NOS3. Conclusion We revealed that a combination of the Arg16Gly and Glu298Asp polymorphisms in ADRB2 and NOS3, respectively, remarkably increased the risk for hypertension in middle-aged and elderly humans.

The mitochondrial-derived peptide MOTS-c: a player in exceptional longevity?

Mitochondrial‐derived peptides (MDP) are encoded by functional short open reading frames in the mitochondrial DNA (mtDNA). These include humanin, and the recently discovered mitochondrial open reading frame of the 12S rRNA‐c (MOTS‐c). Although more research is needed, we suggest that the m.1382A>C polymorphism located in the MOTS‐c encoding mtDNA, which is specific for the Northeast Asian population, may be among the putative biological mechanisms explaining the high longevity of Japanese people.

Age Differences in the Relation Between ACTN3 R577X Polymorphism and Thigh-Muscle Cross-Sectional Area in Women

The relation between ACTN3 R577X polymorphism and muscle mass in women has been reported, but its relation to age remains unclear. We investigated the relationship between ACTN3 R577X polymorphism and muscle mass in both middle-aged and elderly women. Two age groups (middle-aged and older) were formed among 162 healthy, nontraining Japanese women (mean ± SE, 58.6 ± 0.8 year). Their midthigh-muscle cross-sectional area (CSA) was assessed using magnetic resonance imaging, revealing no difference in thigh-muscle CSA among ACTN3 R577X genotypes in the middle-aged group (XX, 87.3 ± 2.5 cm(2); RR&RX, 86.1 ± 1.7 cm(2), p=0.7). In contrast, the XX genotype in the older group had a smaller thigh-muscle CSA adjusted to body weight than the RR&RX genotypes (XX, 67.8 ± 2.0 cm(2); RR&RX, 72.5 ± 1.2 cm(2), p<0.05). The present study showed an association between ACTN3 R577X polymorphism and smaller thigh-muscle CSA in a group of elderly women but not in a group of middle-aged women.

Exceptional longevity and muscle and fitness related genotypes: a functional in vitro analysis and case-control association replication study with SNPs THRH rs7832552, IL6 rs1800795, and ACSL1 rs6552828

There are several gene variants that are candidates to influence functional capacity in long-lived individuals. As such, their potential association with exceptional longevity (EL, i.e., reaching 100+ years) deserves analysis. Among them are rs7832552 in the thyrotropin-releasing hormone receptor (TRHR) gene, rs1800795 in the interleukin-6 (IL6) gene and rs6552828 in the coenzyme A synthetase long-chain 1 (ACSL1) gene. To gain insight into their functionality (which is yet unknown), here we determined for the first time luciferase gene reporter activity at the muscle tissue level in rs7832552 and rs6552828. We then compared allele/genotype frequencies of the 3 abovementioned variants among centenarians [n = 138, age range 100–111 years (114 women)] and healthy controls [n = 334, 20–50 years (141 women)] of the same ethnic and geographic origin (Spain). We also studied healthy centenarians [n = 79, 100–104 years (40 women)] and controls [n = 316, 27–81 years (156 women)] from Italy, and centenarians [n = 742, 100–116 years (623 women)] and healthy controls [n = 499, 23–59 years (356 women)] from Japan. The THRH rs7832552 T-allele and ACSL1 rs6552828 A-allele up-regulated luciferase activity compared to the C and G-allele, respectively (P = 0.001). Yet we found no significant association of EL with rs7832552, rs1800795 or rs6552828 in any of the 3 cohorts. Further research is needed with larger cohorts of centenarians of different origin as well as with younger old people.

Association between ACTN3 R577X Polymorphism and Trunk Flexibility in 2 Different Cohorts

α-Actinin-3 (ACTN3) R577X polymorphism is associated with muscular strength and power. This study was performed to investigate the association between ACTN3 R577X polymorphisms and flexibility as another component of fitness in 2 cohorts. Cohort 1 consisted of 208 men and 568 women (ages 23-88), while Cohort 2 consisted of 529 men and 728 women (ages 23-87). All participants were recruited from the Tokyo metropolitan area and underwent a battery of tests to assess their grip strength and sit-and-reach flexibility. Genotyping results were analyzed for ACTN3 (rs1815739) polymorphism using the TaqMan approach. In Cohort 1, sit-and-reach in the RR genotype (35.3±0.7u2009cm) was significantly lower than those in the RX and XX genotypes (37.2±0.3u2009cm) even after adjusting for sex, age, and exercise habit as covariates (P<0.01). In Cohort 2, sit-and-reach tended to be lower in RR (38.1±0.6u2009cm) than in RX and XX (39.1±0.3u2009cm), but the differences were not significant (P=0.114). Analysis in pooled subjects indicated that RR was associated with significantly lower flexibility than RX and XX (P=0.009). The RR genotype of ACTN3 R577X in the general Japanese population showed lower flexibility compared to the RX and XX genotypes.

Heritability estimates of muscle strength-related phenotypes: A systematic review and meta-analysis

The purpose of this study was to clarify the heritability estimates of human muscle strength‐related phenotypes (H2‐msp). A systematic literature search was conducted using PubMed (through August 22, 2016). Studies reporting the H2‐msp for healthy subjects in a sedentary state were included. Random‐effects models were used to calculate the weighted mean heritability estimates. Moreover, subgroup analyses were performed based on phenotypic categories (eg, grip strength, isotonic strength, jumping ability). Sensitivity analyses were also conducted to investigate potential sources of heterogeneity of H2‐msp, which included age and sex. Twenty‐four articles including 58 measurements were included in the meta‐analysis. The weighted mean H2‐msp for all 58 measurements was 0.52 (95% confidence intervals [CI]: 0.48–0.56), with high heterogeneity (I2=91.0%, P<.001). Subgroup analysis showed that the heritability of isometric grip strength, other isometric strength, isotonic strength, isokinetic strength, jumping ability, and other power measurements was 0.56 (95% CI: 0.46–0.67), 0.49 (0.47–0.52), 0.49 (0.32–0.67), 0.49 (0.37–0.61), 0.55 (0.45–0.65), and 0.51 (0.31–0.70), respectively. The H2‐msp decreased with age (P<.05). In conclusion, our results indicate that the influence of genetic and environmental factors on muscle strength‐related phenotypes is comparable. Moreover, the role of environmental factors increased with age. These findings may contribute toward an understanding of muscle strength‐related phenotypes.

Muscle-Related Polymorphisms (MSTN rs1805086 and ACTN3 rs1815739) Are Not Associated with Exceptional Longevity in Japanese Centenarians.

Myostatin (MSTN) and α-actinin-3 (ACTN3) genes are potentially associated with preservation of muscle mass and oxidative capacity, respectively. To explore the possible role of these genes in exceptional longevity (EL), the allele/genotype frequency distribution of two polymorphisms in MSTN (rs1805086, K153R) and ACTN3 (rs1815739, R577X) was studied in Japanese centenarians of both sexes (n = 742) and healthy controls (n = 814). The rs1805086 R-allele (theoretically associated with muscle mass preservation at the expense of oxidative capacity) was virtually absent in the two groups, where genotype distributions were virtually identical. Likewise, no differences in allele (p = 0.838 (women); p = 0.193 (men); p = 0.587 (both sexes)) or genotype distribution were found between groups for ACTN3 rs1815739 (p = 0.975 (women), p = 0.136 (men), p = 0.752 (both sexes)). Of note, however, the frequency of the rs1805086 R-allele observed here is the lowest been reported to date whereas that of the ‘highly oxidative/efficient’ rs1815739 XX genotype in Japanese male centenarians (33.3%) or supercentenarians of both sexes (≥110 years) are the highest (32.6%), for a non-American population. No definite conclusions can be inferred in relation to EL owing to its lack of association with both rs1815739 and rs1805086. However, it cannot be excluded that these gene variants could eventually be related to a “healthy” metabolic phenotype in the Japanese population. Further research might determine if such metabolic profile is among the factors that can potentially predispose these individuals to live longer than Caucasians and what genetic variants might be actually involved.