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Introduction: Elevated plasma α-klotho (αKl) protects against several ageing phenotypes and has been proposed as a biomarker of a good prognosis for different diseases. The beneficial health effects of elevated plasma levels of soluble αKl (SαKl) have been likened to the positive effects of exercise on ageing and chronic disease progression. It has also been established that molecular responses and adaptations differ according to exercise dose. The aim of this study is to compare the acute SαKl response to different exercise interventions, cardiorespiratory, and strength exercise in healthy, physically active men and to examine the behavior of SαKl 72h after acute strength exercise.Methods: In this quasi-experimental study, plasma SαKl was measured before and after a cardiorespiratory exercise session (CR) in 43 men, and strength exercise session (ST) in 39 men. The behavior of SαKl was also examined 24, 48, and 72h after ST.Results: Significant differences (time×group) were detected in SαKl levels (p=0.001; d=0.86) between CR and ST. After the ST intervention, SαKl behavior varied significantly (p=0.009; d=0.663) in that levels dropped between pre- and post-exercises (p=0.025; d=0.756) and were also significantly higher compared to pre ST values at 24h (p=0.033; d=0.717) and at 48h (p=0.015; d=0.827).Conclusions: SαKl levels increased in response to a single bout of cardiorespiratory exercise; while they decreased immediately after strength exercise, levels were elevated after 24h indicating different klotho protein responses to different forms of exercise.

We studied the influence of genetic polymorphisms involved in the PPARD-PPARGC1A-NRF-TFAM mitochondriogenesis pathway (rs6949152, rs12594956, rs2267668, rs8192678, and rs1937) on muscle phenotypes (thigh muscles’ cross-sectional, maximal handgrip-strength and 30-second chair stand-test) and Barthel index in Caucasian (Spanish) community-dwelling old people (n=75, 21 men, 54 women; 71–94 years). We found no significant genetic associations with the studied phenotypes. Multiple, complex gene-environment and gene-gene interactions which are yet to be determined are likely to play a more determinant role. Resumen Se estudió la influencia de los polimorfismos genéticos implicados en la vía de mitocondriogénesis PPARD-PPARGC1A-NRF-TFAM (rs6949152, rs12594956, rs2267668, rs8192678 y rs1937) en distintos fenotipos musculares (sección transversal muscular del muslo, fuerza máxima de prensión manual y 30 segundos de sentarse-levantarse de una silla) y en el índice de Barthel en personas mayores caucásicas (españoles) (n = 75, 21 hombres, 54 mujeres; 71 a 94 años). No se encontraron asociaciones genéticas significativas con los fenotipos estudiados. Interacciones múltiples, complejos gen-ambiente y relaciones gen-gen aún no determinadas podrían desempeñar un papel más determinante.

There are strong genetic components to cardiorespiratory fitness and its response to exercise training. It would be useful to understand the differences in the genomic profile of highly trained endurance athletes of world class caliber and sedentary controls. An international consortium (GAMES) was established in order to compare elite endurance athletes and ethnicity-matched controls in a case-control study design. Genome-wide association studies were undertaken on two cohorts of elite endurance athletes and controls (GENATHLETE and Japanese endurance runners), from which a panel of 45 promising markers was identified. These markers were tested for replication in seven additional cohorts of endurance athletes and controls: from Australia, Ethiopia, Japan, Kenya, Poland, Russia and Spain. The study is based on a total of 1520 endurance athletes (835 who took part in endurance events in World Championships and/or Olympic Games) and 2760 controls. We hypothesized that world-class athletes are likely to be characterized by an even higher concentration of endurance performance alleles and we performed separate analyses on this subsample. The meta-analysis of all available studies revealed one statistically significant marker (rs558129 at GALNTL6 locus, p = 0.0002), even after correcting for multiple testing. As shown by the low heterogeneity index (I2 = 0), all eight cohorts showed the same direction of association with rs558129, even though p-values varied across the individual studies. In summary, this study did not identify a panel of genomic variants common to these elite endurance athlete groups. Since GAMES was underpowered to identify alleles with small effect sizes, some of the suggestive leads identified should be explored in expanded comparisons of world-class endurance athletes and sedentary controls and in tightly controlled exercise training studies. Such studies have the potential to illuminate the biology not only of world class endurance performance but also of compromised cardiac functions and cardiometabolic diseases.

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.

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.

Exercise phenotypes have played a key role for ensuring survival over human evolution. We speculated that some genetic variants that influence exercise phenotypes could be associated with exceptional survival (i.e. reaching ≥100 years of age). Owing to its effects on muscle structure/function, a potential candidate is the Arg(R)577Ter(X) polymorphism (rs1815739) in ACTN3, the structural gene encoding the skeletal muscle protein α-actinin-3. We compared the ACTN3 R577X genotype/allele frequencies between the following groups of ethnically-matched (Spanish) individuals: centenarians (cases, n = 64; 57 female; age range: 100-108 years), young healthy controls (n = 283, 67 females, 216 males; 21±2 years), and humans who are at the two end-points of exercise capacity phenotypes, i.e. muscle endurance (50 male professional road cyclists) and muscle power (63 male jumpers/sprinters). Although there were no differences in genotype/allele frequencies between centenarians (RR:28.8%; RX:47.5%; XX:23.7%), and controls (RR:31.8%; RX:49.8%; XX:18.4%) or endurance athletes (RR:28.0%; RX:46%; XX:26.0%), we observed a significantly higher frequency of the X allele (P = 0.019) and XX genotype (P = 0.011) in centenarians compared with power athletes (RR:47.6%; RX:36.5%;XX:15.9%). Notably, the frequency of the null XX (α-actinin-3 deficient) genotype in centenarians was the highest ever reported in non-athletic Caucasian populations. In conclusion, despite there were no significant differences with the younger, control population, overall the ACTN3 genotype of centenarians resembles that of world-class elite endurance athletes and differs from that of elite power athletes. Our preliminary data would suggest a certain 'survival' advantage brought about by α-actinin-3 deficiency and the 'endurance'/oxidative muscle phenotype that is commonly associated with this condition.

The Lys(K)153Arg(R) polymorphism in exon 2 (rs1805086, 2379 A>G replacement) of the myostatin (MSTN) gene is a candidate to influence skeletal muscle phenotypes. We examined the association between the MSTN K153R polymorphism and 'explosive' leg power, assessed during sprint (30 m) and stationary jumping tests [squat (SJ) and counter-movement jumps (CMJ)] in non-athletic young adults (University students) [n = 281 (214 men); age: 21-32 years]. We also genotyped the MSTN exonic variants E164K (rs35781413), I225T, and P198A, yet no subject carried any of these variant MSTN alleles. As for the K153R polymorphism, we found only one woman with the KR genotype; thus, we presented the results only for men. The results of a one-way ANCOVA (with age, weight and height entered as covariates) showed that men with the KR genotype (n = 15) had a worse performance in vertical jumps compared with those with the KK genotype [SJ: vertical displacement of center of gravity (CG) of 35.17 ± 1.42 vs. 39.06 ± 0.39 cm, respectively, P = 0.009; CMJ: vertical displacement of CG of 36.44 ± 1.50 vs. 40.63 ± 0.41 cm, respectively, P = 0.008]. The results persisted after adjusting for multiple comparisons according to Bonferroni. Performance in 30 m sprint tests did however not differ by K153R genotypes. In summary, the MSTN K153R polymorphism is associated with the ability to produce 'peak' power during muscle contractions, as assessed with vertical jump tests, in young non-athletic men. Although more research is still needed, this genetic variation is among the numerous candidates to explain, alone or in combination with other polymorphisms, individual variations in muscle phenotypes.