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Understanding genetic contributors to sarcopenia (age-related loss of muscle strength and mass) is key to finding effective therapies. Variants of the bradykinin receptor 2 (BDKRB2) have been linked to athletic and muscle performance. The rs1799722-9 and rs5810761 T alleles have been shown to be overrepresented in endurance athletes, possibly due to increased transcriptional rates of the receptor. These variants have been rarely studied in older people or people with sarcopenia. We performed a post hoc sub-study of the Leucine and ACE (LACE) inhibitor trial, which enrolled 145 participants aged ≥70 years with low grip strength and low gait speed. Participants' blood samples were genotyped for rs179972 using TaqMan and rs5810761 by amplification through Hotstar Taq. Genotypes were compared with outcomes of physical performance and body composition measures. Data from 136 individuals were included in the analysis. For rs1799722 the genotype frequency (TT: 17, CC: 48, CT: 71) remained in Hardy-Weinberg Equilibrium (HWE p = 0.248). There was no difference between the genotypes for six-Minute Walk Distance (6MWD) or Short Physical Performance Battery (SPPB). Men with the TT genotype had a significantly greater 6MWD than other genotypes (TT 400m vs CT 310m vs CC 314m, p = 0.027), and greater leg muscle mass (TT 17.59kg vs CT 15.04kg vs CC 15.65kg, p = 0.007). For rs5810761, the genotype frequency (-9-9: 31, +9+9: 43, -9+9: 60) remained in HWE (p = 0.269). The +9+9 genotype was associated with a significant change in SPPB score at 12 months (-9-9 0 vs -9+9 0 vs +9+9-1, p<0.001), suggesting an improvement. In men, the -9-9 genotype was associated with lower arm fat (-9-9 2.39kg vs -9+9 2.72kg vs +9+9 2.76kg, p = 0.019). In men, the rs1799722 TT genotype was associated with longer 6MWD and greater leg muscle mass, while the rs5810761 -9-9 genotype was associated with lower arm fat mass.

Background: The potential influence of genetics in athletic performance allows the search for genetic profiles associated with muscular work for the orientation of strength training and sports selection. The purpose of the study was to analyze four muscular exercises for effectiveness in improving explosive strength variables, associated to the genetics in Angiotensin Converting Enzyme (ACE) and α-actinin-3 (ACTN3) polymorphisms. Methods: A randomized controlled trial was conducted on a sample of 80 subjects allocated into four groups: concentric muscle work (CMW), eccentric muscle work (EMW), concentric-eccentric muscle (C-EMW) work and isometric muscular work (IMW), by block and gender randomization. Vertical jump, long jump, power jump, and speed were measured to study explosive strength. Genotypic frequencies of ACE (rs4646994) and ACTN3 (rs1815739) were obtained by polymerase chain reaction. Results: ACE gen showed significant improvements regarding the DD genotype in the Sargent test (p = 0.003) and sprint velocity test (p = 0.017). In the ACTN3 gene, the RR variable obtained improvement results with regard to RX and XX variables in long jump (p < 0.001), Sargent test (p < 0.001) and power jump (p = 0.004). Conclusions: The selected genes demonstrated an influence on the muscle work and the improvement in explosive strength variables with a decisive role regarding the type of muscle work performed.

Muscle strength and mass decline in sedentary individuals with aging. The present study investigated the effects of both age and 21 weeks of progressive hypertrophic resistance training (RT) on skeletal muscle size and strength, and on myostatin and myogenin mRNA expression in 21 previously untrained young men (26.0 ± 4.3 years) and 18 older men (61.2 ± 4.1 years) and age-matched controls. Vastus lateralis muscle biopsies were taken before and after RT. Type I and type II muscle fiber cross-sectional areas increased more in young men than in older men after RT ( P  < 0.05). Concentric leg extension increased ( P  < 0.05) more after 10.5 weeks in young men compared to older men, but after 21 weeks no statistical differences existed. The daily energy and protein intake were greater ( P  < 0.001) in young subjects. Both myostatin and myogenin mRNA expression increased in older when compared with young men after RT ( P  < 0.05). In conclusion, after RT, muscle fiber size increased less in older compared to young men. This was associated with lower protein and energy intake and increases in myostatin gene expression in older when compared to young men.

As longevity is increasing, the 65-year-old and older population is projected to increase in the next decades, as are the consequences of age-related muscle deterioration on the quality of life. The purpose of this study was to examine the associations of the ACTN3R577X polymorphism with quality of life and muscular strength in an older Spanish population. In total, 281 older adults participated in this study. Anthropometric measurements, chronic diseases, prescribed medications, quality of life, hand grip strength, and physical activity and nutritional status data were collected. ACTN3 R577X genotyping was determined using Taqman probes. Multivariate regression analysis revealed in adjusted model that, in men, the ACTN3 R577X genotype was significantly associated with hand grip strength (HGS), regression coefficient (β) = 1.23, p = 0.008, dimension 1 of the five-dimension questionnaire EuroQoL (EQ-5D, mobility), (β) = −1.44, p = 0.006, and clinical group risk (CGR) category (β) = −1.38, p = 0.006. In women, a marginal association between the ACTN3 R577X genotype and the CGR category was observed, with a regression coefficient of (β) = −0.97, (p = 0.024). Our findings suggest that the ACTN3 R577X genotype may influence the decline in muscle strength and quality of life in older Spanish adult males.

The purpose of the present study was to evaluate the effects of 8 weeks of strength and power training on the expression of genes related to the canonical WNT pathway and β-catenin protein levels in physically active men. Twenty-five subjects (27.4 ± 4.6 years) were balanced based on their relative maximum strength in the squat exercise (squat 1RM/body mass) and randomly assigned to strength training (ST) ( n  = 10), power training (PT) ( n  = 10), and control (C) ( n  = 5) groups. The ST and the PT groups performed high and low intensity squats, respectively, thrice a week, for 8 weeks. Muscle biopsies from the vastus lateralis muscle were collected before and after the training period. Relative strength and power increased similarly in both ST and PT groups ( P  < 0.001). Fiber cross-sectional area also increased similarly in both ST and PT groups. Gene expression and β-catenin protein expression levels were assessed by real-time PCR and Western blot. Certain genes were up-regulated in the ST group (WNT1: 6.4-fold, P  < 0.0001; SFRP1: 3.3-fold, P  < 0.0001 and LEF1: 7.3-fold, P  < 0.0001) and also in the PT group (WNT1: 24.9-fold, P  < 0.0001; SFRP1: 2.7-fold, P  < 0.0001; LEF1: 34.1-fold, P  < 0.0001 and Cyclin D1: 7.7-fold, P  < 0.001). In addition, the expression of key WNT pathway genes was substantially more responsive to PT than to ST (WNT1: P  < 0.0001; LEF1: P  < 0.0001 and Cyclin D1: P  < 0.001). Finally, the total β-catenin protein content increased only in the PT group ( P  < 0.05). Our data indicate that a PT regimen triggers greater responses in key elements of the WNT pathway.

Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n  = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease ( HLA-DQA1 p  = 4 × 10 −17 ), arthritis ( GDF5 p  = 4 × 10 −13 ), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing. Muscle weakness has been associated with morbidity and mortality in older people. Here, the authors have investigated this trait further by performing a genome-wide meta-analysis of grip strength and Mendelian randomization to discover causal relationships between muscle weakness and other diseases.

Technological advances over the last two decades have placed genetic research at the forefront of sport and exercise science. It provides potential answers to some of contemporary sport and exercise's defining issues and throws up some of the area's most challenging ethical questions, but to date, it has rested on a fragmented and disparate literature base. The Routledge Handbook of Sport and Exercise Systems Genetics constitutes the most authoritative and comprehensive reference in this critical area of study, consolidating knowledge and providing a framework for interpreting future research findings. Taking an approach which covers single gene variations, through genomics, epigenetics, and proteomics, to environmental and dietary influences on genetic mechanisms, the book is divided into seven sections. It examines state-of-the-art genetic methods, applies its approach to physical activity, exercise endurance, muscle strength, and sports performance, and discusses the ethical considerations associated with genetic research in sport and exercise. Made up of contributions from some of the world's leading sport and exercise scientists and including chapters on important topical issues such as gene doping, gender testing, predicting sport performance and injury risk, and using genetic information to inform physical activity and health debates, the handbook is a vital addition to the sport and exercise literature. It is an important reference for any upper-level student, researcher, or practitioner working in the genetics of sport and exercise or exercise physiology, and crucial reading for any social scientist interested in the ethics of sport.

Autophagy has been implicated in the ageing process, but whether autophagy activation extends lifespan in mammals is unknown. Here we show that ubiquitous overexpression of Atg5, a protein essential for autophagosome formation, extends median lifespan of mice by 17.2%. We demonstrate that moderate overexpression of Atg5 in mice enhances autophagy, and that Atg5 transgenic mice showed anti-ageing phenotypes, including leanness, increased insulin sensitivity and improved motor function. Furthermore, mouse embryonic fibroblasts cultured from Atg5 transgenic mice are more tolerant to oxidative damage and cell death induced by oxidative stress, and this tolerance was reversible by treatment with an autophagy inhibitor. Our observations suggest that the leanness and lifespan extension in Atg5 transgenic mice may be the result of increased autophagic activity. Changes in autophagy have been shown to modulate lifespan in lower organisms. Here, Pyo et al. show that mice globally overexpressing the autophagy protein Atg5 live longer and are leaner than normal mice, providing the first evidence that increased autophagy extends lifespan in mammals.

Insertions and deletions (indels) are the second most common type of variation in the human genome. However, limited data on their associations with exercise‐related phenotypes have been documented. The aim of the present study was to examine the association between 18,370 indel variants and power athlete status, followed by additional studies in 357,246 individuals. In the discovery phase, the D allele of the MDM4 gene rs35493922 I/D polymorphism was over‐represented in power athletes compared with control subjects (P = 7.8 × 10−9) and endurance athletes (P = 0.0012). These findings were replicated in independent cohorts, showing a higher D allele frequency in power athletes compared with control subjects (P = 0.016) and endurance athletes (P = 0.031). Furthermore, the D allele was positively associated (P = 0.0013) with greater fat‐free mass in the UK Biobank. MDM4 encodes a protein that inhibits the activity of p53, which induces muscle fibre atrophy. Accordingly, we found that MDM4 expression was significantly higher in the vastus lateralis of power athletes compared with endurance athletes (P = 0.0009) and was positively correlated with the percentage of fast‐twitch muscle fibres (P = 0.0062) and the relative area occupied by fast‐twitch muscle fibres (P = 0.0086). The association between MDM4 gene expression and an increased proportion of fast‐twitch muscle fibres was confirmed in two additional cohorts. Finally, we found that the MDM4 DD genotype was associated with increased MDM4 gene expression in vastus lateralis and greater cross‐sectional area of fast‐twitch muscle fibres. In conclusion, MDM4 is suggested to be a potential regulator of muscle fibre specification and size, with its indel variant being associated with power athlete status. What is the central question of this study? Which indel variants are functional and associated with sport‐ and exercise‐related traits? What is the main finding and its importance? Out of 18,370 tested indels, the MDM4 gene rs35493922 I/D polymorphism was found to be the functional variant (affecting gene expression) and the most significant, with the deletion allele showing associations with power athlete status, fat‐free mass and cross‐sectional area of fast‐twitch muscle fibres. Furthermore, the expression of MDM4 was positively correlated with the percentage of fast‐twitch muscle fibres and the relative area occupied by fast‐twitch muscle fibres.

Important insights concerning the molecular basis of skeletal muscle disuse-atrophy and aging related muscle loss have been obtained in cell culture and animal models, but these regulatory signaling pathways have not previously been studied in aging human muscle. In the present study, muscle atrophy was induced by immobilization in healthy old and young individuals to study the time-course and transcriptional factors underlying human skeletal muscle atrophy. The results reveal that irrespectively of age, mRNA expression levels of MuRF-1 and Atrogin-1 increased in the very initial phase (2-4 days) of human disuse-muscle atrophy along with a marked reduction in PGC-1α and PGC-1β (1-4 days) and a ~10% decrease in myofiber size (4 days). Further, an age-specific decrease in Akt and S6 phosphorylation was observed in young muscle within the first days (1-4 days) of immobilization. In contrast, Akt phosphorylation was unchanged in old muscle after 2 days and increased after 4 days of immobilization. Further, an age-specific down-regulation of MuRF-1 and Atrogin-1 expression levels was observed following 2 weeks of immobilization, along with a slowing atrophy response in aged skeletal muscle. Neither the immediate loss of muscle mass, nor the subsequent age-differentiated signaling responses could be explained by changes in inflammatory mediators, apoptosis markers or autophagy indicators. Collectively, these findings indicate that the time-course and regulation of human skeletal muscle atrophy is age dependent, leading to an attenuated loss in aging skeletal muscle when exposed to longer periods of immobility-induced disuse.