A Genotype-Phenotype Model for Predicting Resistance Training Effects on Leg Press Performance.

This study develops a comprehensive genotype-phenotype model for predicting the effects of resistance training on leg press performance. A cohort of physically inactive adults (N=193) underwent 12 weeks of resistance training, and measurements of maximum isokinetic leg press peak force, muscle mass, and thickness were taken before and after the intervention. Whole-genome genotyping was performed, and genome-wide association analysis identified 85 novel SNPs significantly associated with changes in leg press strength after training. A prediction model was constructed using stepwise linear regression, incorporating seven lead SNPs that explained 40.4% of the training effect variance. The polygenic score showed a significant positive correlation with changes in leg press strength. By integrating genomic markers and phenotypic indicators, the comprehensive prediction model explained 75.4% of the variance in the training effect. Additionally, five SNPs were found to potentially impact muscle contraction, metabolism, growth, and development through their association with REACTOME pathways. Individual responses to resistance training varied, with changes in leg press strength ranging from -55.83% to 151.20%. The study highlights the importance of genetic factors in predicting training outcomes and provides insights into the potential biological functions underlying resistance training effects. The comprehensive model offers valuable guidance for personalized fitness programs based on individual genetic profiles and phenotypic characteristics.

Comparison of energy expenditure and substrate metabolism during overground and motorized treadmill running in Chinese middle-aged women.

The purpose of this study was to compare differences of energy expenditure and substrate metabolism between motorized-treadmill and overground running in three different velocities in Chinese middle-aged women. In total, 74 healthy middle-aged women (age, 48 ± 4 years; height, 159.4 ± 4.9 cm; weight, 58.6 ± 6.7 kg; and body-mass index (BMI), 23.1 ± 2.7 kg/m2) volunteered to participate in this study. Bioelectrical-impedance analysis was used to measure body composition. Energy expenditure, carbohydrates (CHO), and fat oxidation were calculated with indirect calorimetry during motorized-treadmill and overground running. Running speed from slow to fast was 7.0, 8.0, and 9.0 km/h. The duration of each velocity was 6 min, separated by 5-15 min rest. There was no significant difference in energy expenditure between overground and treadmill running at the speed of 7 km/h (8.10 ± 1.25 vs. 7.75 ± 1.13 kcal/min, p > 0.05). Energy expenditure of overground running at 8 and 9 km/h was higher than that of treadmill running (9.36 ± 1.40 vs. 8.54 ± 1.21 kcal/min; 10.33 ± 1.55 vs. 9.54 ± 1.36 kcal/min; both p < 0.01). Fat contribution to energy consumption was significantly higher during treadmill running than during overground running (both p < 0.01) at speeds of 8 and 9 km/h. Overground running at high intensity incurred greater energy consumption than treadmill running did. However, results showed greater fat utilization during treadmill running than during overground running at high intensity. It is critical that these differences are taken into account when we prescribe training modes and intensities for 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.

[Advance on exercise and health genomics and metabolomics].

Kinetism and fitness effects have high heritability. 10%~20% of people experiences no effects or lower 5% after exercise training, and the adverse responders also reached 10%-20%. Genomics and metabolomics are introduced to expound the individual difference and molecular mechanism that exercise training benefits health. In this essay, the research progress is reviewed.

FNDC5 (irisin) gene and exceptional longevity: a functional replication study with rs16835198 and rs726344 SNPs.

Irisin might play an important role in reducing the risk of obesity, insulin resistance, or several related diseases, and high irisin levels may contribute to successful aging. Thus, the irisin precursor (FNDC5) gene is a candidate to influence exceptional longevity (EL), i.e., being a centenarian. It has been recently shown that two single-nucleotide polymorphisms (SNPs) in the FNDC5 gene, rs16835198 and rs726344, are associated with in vivo insulin sensitivity in adults. We determined luciferase gene reporter activity in the two above-mentioned SNPs and studied genotype distributions among centenarians (n = 175, 144 women) and healthy controls (n = 347, 142 women) from Spain. We also studied an Italian [79 healthy centenarians (40 women) and 316 healthy controls (156 women)] and a Japanese cohort [742 centenarians (623 women) and 499 healthy controls (356 women)]. The rs726344 SNP had functional significance, as shown by differences in luciferase activity between the constructs of this SNP (all P ≤ 0.05), with the variant A-allele having higher luciferase activity compared with the G-allele (P = 0.04). For the rs16835198 SNP, the variant T-allele tended to show higher luciferase activity compared with the G-allele (P = 0.07). However, we found no differences between genotype/allele frequencies of the two SNPs in centenarians versus controls in any cohort, and no significant association (using logistic regression adjusted by sex) between the two SNPs and EL. Further research is needed with different cohorts as well as with additional variants in the FNDC5 gene or in other genes involved in irisin signaling.

The effect of baduanjin on promoting the physical fitness and health of adults.

The purpose of study was to assess the efficacy of a 16-week Baduanjin qigong training intervention in promoting physical fitness and health for adults. An experimental design was adopted, and subjects were assigned randomly into an experimental group (n = 55) and a control group (n = 55). In the intervention group comprised of adults, there were no significant variations in blood glucose, blood lipid, blood pressure, heart rate variability, and vital capacity indices. The body weight and body mass index (BMI) dropped in the intervention group. Compared with the control group, the skinfold thicknesses decreased at lower corner of scapula, triceps brachii, and abdomen, with a statistical significance (P < 0.001; P = 0.005; P = 0.003). By comparing the physical fitness indices, it was found that the increase of the results of sit-and-reach test in the intervention group had statistical significance (P = 0.001). In conclusion, it was found by our trial that Baduanjin exercise could significantly improve the physical flexibility and subcutaneous adipose accumulation in the healthy adults.

PTK2 rs7460 and rs7843014 polymorphisms and exceptional longevity: a functional replication study.

Focal adhesion is critical for cell survival. The focal adhesion kinase (FAK, or PTK2) is an important component of the human interactome and thus is a potential longevity-related protein. Here we studied the association between two PTK2 gene single-nucleotide polymorphisms (SNPs) (rs7843014, rs7460) and exceptional longevity (EL). In addition to gaining insight into their functionality by determining luciferase gene reporter activity, we studied the genotype/allele frequency of these two SNPs among three different cohorts: (1) Spanish centenarians (n=175, 100-111 years, 144 women) and healthy controls (n=355, 20-50 years, 284 women); (2) Italian centenarians (n=79, 100-104 years, 40 women) and controls (n=316, 29-50 years, 156 women); and (3) Japanese centenarians (n=742, 100-116 years, 623 women) and healthy controls (n=499, 23-59 years, 356 women). Both SNPs had functional significance, with the A allele up-regulating luciferase activity compared to the other allele (rs7460 T allele and rs7843014 C allele, respectively). The A allele of both SNPs was negatively associated with EL in the Spanish cohort (rs7460, odds ratio [OR] adjusted by sex=0.40, 95% confidence intervals [CI] 0.3, 0.6, p<0.001); rs7843014, OR=0.37, 95% CI 0.3, 0.5, p<0.001). The OR of being a centenarian if having the rs7460-TT genotype was 6.68 (95% CI 4.1, 10.8, p<0.001). The rs7843014 CC genotype was also positively associated with EL (OR=7.58, 95% CI 4.6, 12.3, p<0.001]. No association was, however, found for the Italian or Japanese cohorts. Thus, two genotypes of the FAK gene, rs7460 TT and rs7843014 CC, are possibly associated with lower gene expression and might favor the likelihood of reaching EL in the Spanish population. Further research is needed to unveil the mechanisms by which FAK expression could perhaps influence the rate of aging.

Heart rate variability threshold values for early-warning nonfunctional overreaching in elite female wrestlers.

Functional overreaching (FOR) represents intense training followed by a brief reduction in performance and then a rapid recovery (<2 weeks) and performance supercompensation. Nonfunctional overreaching (NFOR) occurs when the reduced performance continues ≥3 weeks. Heart rate variability (HRV) is a promising tool for detecting NFOR. In this study, the authors examined HRV thresholds in 34 elite female wrestlers (mean ± SD: age 23 ± 3 years; height 165.6 ± 6 cm, weight 63 ± 8 kg) for FOR/NFOR during training before 11 major competitions. Supine HRV was analyzed weekly at the same time of day using time and frequency domain methods. The authors observed that the time domain index, square root of the mean of the sum of the squares of differences between adjacent R-to-R intervals (rMSSD, milliseconds), denoting parasympathetic tone, showed those responding normally to training (82.76 ms, 95% confidence interval 77.75-87.78) to be significantly different to those showing a decrease (45.97 ms, 95% confidence interval, 30.79-61.14) or hyper-responsiveness (160.44 ms, 95% confidence interval, 142.02-178.85; all, p < 0.001). Similar results were observed for mixed sympathetic and parasympathetic signal standard deviation of the NN intervals (ms): normal (65.39; 95% confidence interval, 62.49-68.29), decrease (40.07; 95% confidence interval, 29-51.14), and hyperresponse (115.00; 95% confidence interval, 105.46-124.54; all, p < 0.001) and synonymous frequency domain components. An examination of the 95% confidence interval shows a narrow band surrounding a normal response compared with broader bands accompanying adverse responses. Thus, severe perturbations both above and below normal responses lasting >2 weeks indicated an athlete's transition to NFOR and, hence, are useful for assessing possible overreaching/training.

Acyl coenzyme A synthetase long-chain 1 (ACSL1) gene polymorphism (rs6552828) and elite endurance athletic status: a replication study.

The aim of this study was to determine the association between the rs6552828 polymorphism in acyl coenzyme A synthetase (ACSL1) and elite endurance athletic status. We studied 82 Caucasian (Spanish) World/Olympic-class endurance male athletes, and a group of sex and ethnically matched healthy young adults (controls, n=197). The analyses were replicated in a cohort of a different ethnic origin (Chinese of the Han ethnic group), composed of elite endurance athletes (runners) [cases, n=241 (128 male)] and healthy sedentary adults [controls, n=504 (267 male)]. In the Spanish cohort, genotype (P=0.591) and minor allele (A) frequencies were similar in cases and controls (P=0.978). In the Chinese cohort, genotype (P=0.973) and minor allele (G) frequencies were comparable in female endurance athletes and sedentary controls (P=0.881), whereas in males the frequency of the G allele was higher in endurance athletes (0.40) compared with their controls (0.32, P=0.040). The odds ratio (95%CI) for an elite endurance Chinese athlete to carry the G allele compared with ethnically matched controls was 1.381 (1.015-1.880) (P-value=0.04). Our findings suggest that the ACSL1 gene polymorphism rs6552828 is not associated with elite endurance athletic status in Caucasians, yet a marginal association seems to exist for the Chinese (Han) male population.

Are calcineurin genes associated with athletic status? A function, replication study.

PURPOSE: Polymorphisms in calcineurin genes are candidates to explain individual variations in endurance sports performance owing to the pivotal role that the calcineurin signaling pathway plays in the regulation of important cardiac and skeletal muscle phenotypes. METHODS: We compared genotypic/allelic frequencies in 55 single nucleotide polymorphisms (SNP) of the five genes (PPP3CA, PPP3CB, PPP3CC, PPP3R1, and PPP3R2) encoding the calcineurin protein subunits between 123 elite runners (cases, n = 61 women) and 125 healthy nonathletes (controls, n = 56 women) from the same ethnic background (Han Chinese) and used the dual-luciferase reporter assay to analyze the functional significance of the associated SNP. RESULTS: The C allele of the PPP3CA rs3804358 polymorphism was overrepresented in athletes (17%) compared with controls (8%) (P = 0.003), whereas the T allele of the PPP3CB rs3763679 polymorphism was underrepresented in athletes (23%) compared with controls (37%) (P = 0.001). The luciferase reporter constructs containing C allele of the rs3804358 and rs3763679 polymorphisms produced significantly greater luciferase activity than that of the G or T alleles, respectively. However, the results on the two aforementioned polymorphisms were not corroborated in a Caucasian (Spanish) cohort of male elite endurance athletes (n = 100) and nonathletic male controls (n = 175). CONCLUSIONS: Although there are large differences between ethnicities and more research is needed, our findings suggest that intronic polymorphisms of the calcineurin genes have functional significance and show evidence of association with elite endurance performance in the northern Han Chinese population.

Polymorphisms in the calcineurin genes are associated with the training responsiveness of cardiac phenotypes in Chinese young adults.

We studied the association of 55 polymorphisms in the PPP3CA, PPP3CB, PPP3CC, PPP3R1 and PPP3R2 genes with both (1) the pre-training levels and (2) responsiveness to endurance training (18 weeks), of echocardiographic variables. The latter were measured both before and after the training program at each of the following time points: before (rest), during and after cycle-ergometry exercise. Subjects were healthy young Chinese men of Han origin [n = 102; mean (SD) age: 19 ± 1 years]. To assess genotype:phenotype associations at pre-training, we used a one-factor (genotype) ANOVA for each polymorphism. To assess the association between each polymorphism and the training responsiveness of cardiac phenotypes, we used a two-factor (genotype x training) ANOVA with repeated measures. All multiple comparisons were corrected for mass significance. For genotype:phenotype associations at pre-training, we only found a significant association between the rs3763679 polymorphism (PPP3CB) and resting heart rate. As for genotype associations with trainability of cardiac phenotypes, we found the following significant associations (i.e. significant genotype × training interaction effect): (1) rs1879793, rs1075534, rs7430, rs2461483 and rs10108011 (PPP3CC) and cardiac output/stroke volume after exercise; and (2) rs1407877 (PPP3R2) and ejection fraction at 50 W. The findings suggest that polymorphisms in the calcineurin genes might be among the numerous potential genetic variant candidates that can help explaining human variations in the pre-training levels or trainability of cardiac phenotype traits.

Are calcineurin genes associated with endurance phenotype traits?

Polymorphisms in calcineurin genes are candidates to explain individual variations in endurance phenotype traits owing to the pivotal role that the calcineurin signaling pathway plays in the regulation of important cardiac and skeletal muscle phenotypes such as slow myosin heavy chain expression, skeletal muscle oxidative capacity or cardiac hypertrophy. We studied the possible association of 55 polymorphisms in the calcineurin gene isoforms PPP3CA, PPP3CB, PPP3CC, PPP3R1 and PPP3R2 with both baseline levels and responsiveness to a 18-week endurance training program of maximal oxygen uptake (VO(2)max) and running economy (RE) in healthy young Chinese men [n = 102; mean (SD) age 19 +/- 1 years] of Han origin. We used two-way (genotype, training) ANOVA for repeated measures to compare baseline and trainability of VO(2)max and RE among genotypes of the aforementioned polymorphisms. We found a significant association between (a) baseline VO(2)max and the rs2850965 and rs3804423 polymorphisms in the PPP3CA gene; (b) training responsiveness of VO(2)max and both the rs3804358 polymorphism (PPP3CA) and the rs4671887 polymorphism (PPP3R1); and (c) training responsiveness of RE and rs3739723 (PPP3R2). Though more research is needed, our findings suggest that polymorphisms in the calcineurin genes might be among the numerous potential genetic variant candidates that, together with other factors (e.g., environment, complex genetics interactions), can help explaining human variations in endurance exercise phenotype traits.