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It is clear, based on a deep scientific literature base, that genetic and genomic factors play significant roles in determining a wide range of sport and exercise characteristics including exercise endurance capacity, strength, daily physical activity levels, and trainability of both endurance and strength. Although the research field of exercise systems genetics has rapidly expanded over the past two decades, many researchers publishing in this field are not extensively trained in molecular biology or genomics techniques, sometimes creating gaps in generating high-quality and cutting-edge research for publication. As current or former Associate Editors for Medicine and Science in Sports and Exercise that have handled the majority of exercise genetics articles for Medicine and Science in Sports and Exercise in the past 15 yr, we have observed a large number of scientific manuscripts submitted for publication review that have exhibited significant flaws preventing their publication; flaws that often directly stem from a lack of knowledge regarding the "state-of-the-art" methods and accepted literature base that is rapidly changing as the field evolves. The purpose of this commentary is to provide researchers—especially those coming from a nongenetics background attempting to publish in the exercise system genetics area—with recommendations regarding best-practice research standards and data analysis in the field of exercise systems genetics, to strengthen the overall literature in this important and evolving field of research. [ABSTRACT FROM AUTHOR]

The article presents an overview of a review of exercise genomics literature which was conducted in an effort to investigate advances which had been seen in exercise, fitness and performance genomics in 2011. After reviewing several research studies which were published in the genomics literature, researchers concluded that a strong exercise genomics body of evidence would not only translate into powerful genomic predictors but also have a major effect on exercise biology and exercise behavior research.

Physical activity is associated with reduced risk of several age-related diseases as well as with increased longevity in both rodents and humans. Though these associations are well established, evidence of the molecular and cellular factors associated with reduced disease risk and increased longevity resulting from physical activity is sparse. A long-standing hypothesis of aging is the telomere hypothesis: as a cell divides, telomeres shorten resulting eventually in replicative senescence and an aged phenotype. Several reports have recently associated telomeres and telomere-related proteins to diseases associated with physical inactivity and aging including cardiovascular disease, insulin resistance, and hypertension. Interestingly several reports have also shown that longer telomeres are associated with higher physical activity levels, indicating a potential mechanistic link between physical activity, reduced agerelated disease risk, and longevity. The primary purpose of this review is to discuss the potential importance of physical activity in telomere biology in the context of inactivity- and age-related diseases. A secondary purpose is to explore potential mechanisms and important avenues for future research in the field of telomeres and diseases associated with physical inactivity and aging. [ABSTRACT FROM AUTHOR]

The article focuses on studies related to performance genomics and the correlation between physical activity and the genetic make-up of an individual. It states that certain studies reveal that genetic factors affect an individual's level of activeness. The genome-wide association study (GWAS) and its publication in 2009 was noted to compensate for the scarcity of data on the functions of DNA on the emergence of genetic variance that influence physical activity. It mentions that much of the studies published on the topic of genetic function in cardiorespiratory endurance are centered on genes acted upon by the nuclear genome. The functions of Apolipoprotein E in lipid metabolism are also cited. Moreover, it suggests that exercise scientists should arrive at high-quality research designs.

Previous reports have shown a lower proportion of the ACTN3 X/X genotype (R577X nonsense polymorphism) in sprint-related athletes compared to the general population, possibly attributed to impairment of muscle function related to α-actinin-3 deficiency. In the present study, we examined the frequency of the X/X genotype in both Black and White elite-level bodybuilders and strength athletes in comparison to the general population. A reference population of 668 Whites (363 men and 305 women) and 208 Blacks (98 men and 110 women) was genotyped for the ACTN3 R577X polymorphism. Strength athletes (52 white and 23 black; 4 women) consisting predominantly of world class and locally competitive bodybuilders, and elite powerlifters were recruited and similarly genotyped. Significantly lower X/X genotype frequencies were observed in the athletes (6.7%) vs controls (16.3%; P=0.005). The X/X genotype was significantly lower in White athletes (9.7%) vs controls (19.9%; P=0.018). No black athletes (0%) were observed with the X/X genotype, though this finding only approached statistical significance vs controls (4.8%; P=0.10). The results indicate that the ACTN3 R577X nonsense allele (X) is under-represented in elite strength athletes, consistent with previous reports indicating that α-actinin-3 deficiency appears to impair muscle performance.European Journal of Human Genetics (2008) 16, 391–394; doi:10.1038/sj.ejhg.5201964; published online 28 November 2007 [ABSTRACT FROM AUTHOR]

Background:Approximately 5% of patients administered gentamicin (GM), an aminoglycoside antibiotic, experience vestibular ototoxicity resulting in balance dysfunction. In the present study, we sought to identify susceptibility genes associated with GM-induced vestibular dysfunction using a case/control design. Methods: White cases (n = 137; 55 men, 82 women) were recruited based on physician-confirmed unilateral or bilateral vestibular dysfunction attributed to GM administration. Controls (n = 126; 54 men, 72 women) were healthy, age-matched individuals without vestibular dysfunction or balance impairment. Buccal cell samples were obtained from all subjects and DNA was genotyped for 15 polymorphisms in 9 genes. Candidate genes were identified primarily for their roles in oxidative stress based on predicted mechanisms of gentamicin-induced ototoxicity. Statistical analyses included the multi-dimensionality reduction (MDR) method for identifying gene x gene interactions across multiple candidate genes. Results: Both single gene and MDR analyses revealed the NOS3 (ENOS) p.Glu298Asp polymorphism as significantly associated with GM-induced vestibular dysfunction (both p ⩽ 0.03). MDR analysis revealed a three-gene combination, consisting of NOS3 (p.Glu298Asp), GSTZ1 (p.Lys32Glu), and GSTP1 (p.Ile105Val), that provided the highest predictive model for GM-induced vestibular dysfunction (64% accuracy; p = 0.009). Conclusions: The results indicate that carriers of risk alleles at three oxidative stress-related genes have increased susceptibility to GM-induced vestibular dysfunction. [ABSTRACT FROM AUTHOR]

Abstract: Peripheral vasculature resistance can play an important role in affecting blood pressure and the development of cardiovascular disease. A better understanding of the genes that encode vasodilators, such as adenosine, will provide insight into the mechanisms underlying cardiovascular disease. We tested whether the adenosine monophosphate deaminase-1 (AMPD1) C34T gene polymorphism was associated with the vasodilatory response to ischemia in Caucasian females aged 18–35 years. Blood samples (n =58) were analyzed for the C34T variant and resulted in the following genotype groups: CC (n =45) and CT (n =13). Mean blood pressure (MBP), heart rate, and forearm blood flow (FBF) measured by venous occlusion plethysmography were measured at baseline and at 1 (peak FBF), 2 and 3 min of vasodilation during reactive hyperemia following 5 min of arm ischemia. To control for interindividual variability in baseline FBF and forearm vascular resistance (FVR) the percent change in FBF and FVR were calculated for each min. The percent decrease in FVR was significantly greater in the CT compared to the CC genotype group (−40±4% vs. −24±3%, P =0.01) during the 2nd min of reactive hyperemia. The percent increase in FBF tended to be greater in the CT compared to the CC genotype group (+69±9% vs. +42±9%, P =0.07) during the 2nd min of reactive hyperemia after adjustment for percent body fat. Consistent with previous findings of increased production of adenosine during exercise in individuals carrying a T allele, our findings suggest that the AMPD1 C34T polymorphism is associated with vasodilatory response to ischemia in the peripheral vasculature because individuals with the T allele had a greater vasodilatory response to ischemia. [Copyright &y& Elsevier]

This study assessed age and sex effects on muscle fibre adaptations to heavy-resistance strength training (ST). Twenty-two young men and women (20–30 years old) and 18 older men and women (65–75 years old) completed 9 weeks of heavy-resistance knee extension exercises with the dominant leg 3 days week−1; the non-dominant leg served as a within-subject, untrained control. Bilateral vastus lateralis muscle biopsies were obtained before and after ST for analysis of type I, IIa and IIx muscle fibre cross-sectional area (CSA) and fibre type distribution. One-repetition maximum (1-RM) strength was also assessed before and after ST. ST resulted in increased CSA of type I, IIa and IIx muscle fibres in the trained leg of young men, type I and IIa fibres in young women, type IIa fibres in older men, and type IIx fibres in older women (all P < 0.05). Analysis of fibre type distribution revealed a significant increase in the percentage of type I fibres ( P < 0.05) along with a decrease in type IIx fibres ( P= 0.054) after ST only in young women. There were no significant changes in muscle fibre CSA or fibre type distribution in the untrained leg for any group. All groups displayed significant increases in 1-RM (27–39%; all P < 0.01). In summary, ST led to significant increases in 1-RM and type II fibre CSA in all groups; however, age and sex influence specific muscle fibre subtype responses to ST. [ABSTRACT FROM AUTHOR]

We investigated the association of vitamin D receptor (VDR) genotype with fat-free mass (FFM) in a cohort of 302 older (aged 58-93 years) Caucasian men who underwent body composition analysis by dual-energy X-ray absorptiometry, and completed questionnaires addressing comorbidities, physical activity, and dietary intake. All participants were genotyped for a VDR translation start site (FokI) polymorphism [FF (37.7%), Ff (48.4%), and ff (13.9%)] and the previously studied BsmI polymorphism [BB (24.9%), Bb (37.7%), and bb (37.4%)]. The BsmI polymorphism was not associated with FFM in any analysis; however, the FokI polymorphism was significantly associated with total FFM, appendicular FFM, and relative (kg/m(2)) appendicular FFM (all p <.05), with the FF group demonstrating significantly lower FFM than the Ff and ff groups (e.g., total FFM: FF = 57.6 +/- 0.4, Ff = 59.4 +/- 0.4, ff = 59.4 +/- 0.7 kg; p <.02). Age-adjusted logistic regression revealed a 2.17-fold higher risk for sarcopenia (defined previously as appendicular FFM <7.26 kg/m(2)) in FF homozygotes (95% CI [confidence interval] = 1.19-3.85; p =.03) compared to men with one or more f alleles. The VDR translation start site (FokI) polymorphism is significantly associated with FFM and sarcopenia in this cohort of older Caucasian men. [ABSTRACT FROM AUTHOR]

We studied the association of the G-174C promoter polymorphism in the interleukin-6 gene (IL6) with total body fat and fat-free mass (FFM) in 242 men and women (IL6 genotypes: G/G, n = 87; G/C, n = 100; C/C, n = 55) across the adult age span (21-92 years). In men, but not women (significant genotype by sex interactions; p =.023-.048), the C/C group exhibited significantly lower total FFM than the G/G group (54.7 +/- 0.8 kg vs 57.2 +/- 0.7 kg, respectively, p =.020), as well as significantly lower FFM of the lower limbs compared with the G/G group (18.4 +/- 0.3 kg vs 19.8 +/- 0.3 kg, respectively, p =.004). No significant genotype differences were observed in total body fat mass in either men or women. The results indicate that the IL6 G-174C polymorphism is significantly associated with FFM in men but not women. [ABSTRACT FROM AUTHOR]

We studied the association of the G-174C promoter polymorphism in the interleukin-6 gene (IL6) with total body fat and fat-free mass (FFM) in 242 men and women (IL6 genotypes: G/G, n = 87; G/C, n = 100; C/C, n = 55) across the adult age span (21-92 years). In men, but not women (significant genotype by sex interactions; p = .023-.048), the C/C group exhibited significantly lower total FFM than the G/G group (54.7 ± 0.8 kg vs 57.2 ± 0.7 kg, respectively, p = .020), as well as significantly lower FFM of the lower limbs compared with the G/G group (18.4 ± 0.3 kg vs 19.8 ± 0.3 kg, respectively, p = .004). No significant genotype differences were observed in total body fat mass in either men or women. The results indicate that the IL6 G-174C polymorphism is significantly associated with FFM in men but not women. [ABSTRACT FROM AUTHOR]

Testosterone (T) supplementation in men induces muscle fiber hypertrophy. We hypothesized that T-induced increase in muscle fiber size is associated with a dose-dependent increase in satellite cell number. We quantitated satellite cell and myonuclear number by using direct counting and spatial orientation methods in biopsies of vastus lateralis obtained at baseline and after 20 wk of treatment with a gonadotropin-releasing hormone agonist and a 125-, 300-, or 600-mg weekly dose of enanthate. T administration was associated with a significant increase in myonuclear number in men receiving 300- and 600-mg doses. The posttreatment percent satellite cell number, obtained by direct counting, differed significantly among the three groups (ANCOVA P < 0.000001); the mean posttreatment values (5.0 and 15.0%) in men treated with 300- and 600-mg doses were greater than baseline (2.5 and 2.5%, respectively, P < 0.05 vs. baseline). The absolute satellite cell number measured by spatial orientation at 20 wk (1.5 and 4.0/mm) was significantly greater than baseline (0.3 and 0.6/mm) in men receiving the 300- and 600-mg doses (P < 0.05). The change in percent satellite cell number correlated with changes in total (r = 0.548) and free T concentrations (r = 0.468). Satellite cell and mitochondrial areas were significantly higher and the nuclear-to-cytoplasmic ratio lower after treatment with 300- and 600-mg doses. We conclude that T-induced muscle fiber hypertrophy is associated with an increase in satellite cell number, a proportionate increase in myonuclear number, and changes in satellite cell ultrastructure. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To examine the possible influences of age and gender on muscle volume responses to strength training (ST). DESIGN: Prospective intervention study. SETTING: University of Maryland Exercise Science and Wellness Research Laboratories. PARTICIPANTS: Eight young men (age 20–30 years), six young women (age 20–30 years), nine older men (age 65–75 years), and ten older women (age 65–75 years). INTERVENTION: A 6-month whole-body ST program that exercised all major muscle groups of the upper and lower body 3 days/week. MEASUREMENTS: Thigh and quadriceps muscle volumes and mid-thigh muscle cross-sectional area (CSA) were assessed by magnetic resonance imaging before and after the ST program. RESULTS: Thigh and quadriceps muscle volume increased significantly in all age and gender groups as a result of ST (P < .001), with no significant differences between the groups. Modest correlations were observed between both the change in quadriceps versus the change in total thigh muscle volume (r = 0.65; P < .001) and the change in thigh muscle volume versus the change in mid-thigh CSA (r = 0.76, P < .001). CONCLUSIONS: The results indicate that neither age nor gender affects muscle volume response to whole-body ST. Muscle volume, rather than muscle CSA, is recommended for studying muscle mass responses to ST. [ABSTRACT FROM AUTHOR]

Presents information on a study which compared muscle mass responses of young and older men and women to the same relative strength training and detraining protocols. Methodology; Results of the study; Discussion.

PURPOSE: To identify susceptibility genes associated with gentamicin-(GM; an aminoglycoside antibiotic) induced vestibular dysfunction. METHODS: A case/control analysis was performed. White cases (n=137; 55 men, 82 women) were recruited based on physician-confirmed unilateral or bilateral vestibular dysfunction attributed to GM administration. Controls (n=126; 54 men, 72 women) were healthy, age-matched individuals without vestibular dysfunction or balance impairment. Buccal cell samples were obtained from all subjects and DNA was genotyped for 15 polymorphisms in 9 genes. Statistical analyses included the multi-dimensionality reduction (MDR) method for identifying gene x gene interactions across multiple candidate genes. RESULTS: Both single gene and MDR analyses revealed that the ENOS Glu298Asp polymorphism was significantly associated with GM-induced vestibular dysfunction (both P<0.05). MDR analysis revealed a three-gene combination, consisting of ENOS (Glu298Asp), GSTZ1 (Lys32Glu), and GSTP1 (Ile105Val), that provided the highest predictive model for GM-induced vestibular dysfunction (64% accuracy; p=0.001). CONCLUSION: The results indicate that carriers of risk alleles at three oxidative stress-related genes have increased susceptibility to GM-induced vestibular dysfunction. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "ACE ID genotype and the muscle strength and size response to unilateral resistance training," by L.S. Pescatello, M.A. Kostek, H. Gordish-Dressman and others in an issue in 2006.

Aging is associated with a tissue degeneration phenotype marked by a loss of tissue regenerative capacity. Regenerative capacity is dictated by environmental and genetic factors that govern the balance between damage and repair. The age-associated changes in the ability of tissues to replace lost or damaged cells is partly the cause of many age-related diseases such as Alzheimer's disease, cardiovascular disease, type II diabetes, and sarcopenia. A well-established marker of the aging process is the length of the protective cap at the ends of chromosomes, called telomeres. Telomeres shorten with each cell division and with increasing chronological age and short telomeres have been associated with a range of age-related diseases. Several studies have shown that chronic exposure to exercise (i.e., exercise training) is associated with telomere length maintenance; however, recent evidence points out several controversial issues concerning tissue-specific telomere length responses. The goals of the review are to familiarize the reader with the current telomere dogma, review the literature exploring the interactions of exercise with telomere phenotypes, discuss the mechanistic research relating telomere dynamics to exercise stimuli, and finally propose future directions for work related to telomeres and physiological stress. [ABSTRACT FROM AUTHOR]

Angiotensin II (AngII), via the AngII type 1 receptor (AT1R), contributes to oxidative stress. Aerobic exercise training (AEXT) reduces the risk of cardiovascular (CV) disease, presumably by reducing the grade of oxidative stress. We investigated the independent and combined influence of the AGTR1 A1166C and -825 T/A polymorphisms on oxidative stress and plasma AngII responses to AEXT in pre- and stage 1 hypertensives. Urinary 8-iso-PGF2α significantly increased with AEXT (p=0.002); however, there were no significant changes in superoxide dismutase activity or AngII levels. There was a significant difference in the change in AngII levels with AEXT between A1166C genotype groups (p=0.04) resulting in a significant interactive effect of the A1166C polymorphism and AEXT on the change in AngII (p<0.05). Only the TT genotype group of the -825 T/A polymorphism had a significant reduction in plasma AngII (p=0.02). Risk allele analysis revealed a significant reduction in plasma AngII (p=0.04) and a significant increase in urinary 8-iso-PGF2α (p=0.01) with AEXT in individuals with two risk alleles only. Our findings suggest that variation in the AGTR1 gene is associated with differential changes in plasma AngII but not oxidative stress. [ABSTRACT FROM AUTHOR]

Background. There is little information regarding the effects of strength training on intermuscular fat (IMF). This study examines changes in IMF in response to strength training in carriers of the adrenergic receptor (ADR) β2Glu27 polymorphism versus noncarriers and between carriers of ADRα2b Glu9 polymorphism versus noncarriers. Methods. Midthigh IMF and muscle area were measured by computed tomography (CT) before and after 10 weeks of single-leg strength training in healthy, sedentary middle-aged and older (50-83 years) men (n = 46) and women (n = 52) in both their trained and untrained (control) legs. Results. The strength training program resulted in a substantial increase in one-repetition maximum strength (p < .001 ) and muscle area (p < .001 ), but no significant changes in IMF in the whole group. However, IMF was significantly reduced with strength training in participants carrying ADRβ2 Glu27 (-2. 3 ± 1.0 cm². p = .028), but no significant change was observed with ADRβ2 Glu27 noncarriers. The decrease in IMF in ADRα2b Glu9 carriers (-1.9 ± 1.0 cm², p = .066) was significantly different (2.9 ± 1.5 cm², p = .043) from a nonsignificant increase in ADRα2b Glu9 noncarriers. ADRβ2 Glu27 carriers who also carried ADRα2b Glu9 significantly lost IMF with strength training (-3.8 ± 1.5 cm², p = .018). Conclusion. ADR genotype influences IMF response to strength training. [ABSTRACT FROM AUTHOR]

Acute exercise has been shown to improve memory in humans. Potential mechanisms include increased Bdnf expression, noradrenergic activity and modification of glutamate receptors. Because mice are commonly used to study exercise and brain plasticity, it is important to explore how acute exercise impacts behavior in this model. C57BL/6J mice were assigned to three groups: control, moderate‐intensity running, and high‐intensity running. Control mice were placed on a stationary treadmill for 30 minutes and moderate‐ and high‐intensity mice ran for 30 minutes at 12 and 15‐17 m/min, respectively. Mice were sacrificed immediately after running and the hippocampus removed. Total Bdnf, Bdnf exon IV, and glutamate receptor subunits were quantified with quantitative polymerase chain reaction. Total and phosphorylated GluR1 (Ser845 and Ser831) protein was quantified following immunoblotting. Utilizing the same protocol for control and high‐intensity running, object location memory was examined in a separate cohort of mice. Anxiety‐like behavior was assessed in the open field task (OFT) in a third cohort of mice that were separated into four groups: control‐saline, control‐DSP‐4, acute exercise‐saline, and acute exercise‐DSP‐4. DSP‐4 was used to lesion the central noradrenergic system. We observed higher Bdnf IV mRNA in high‐intensity runners compared to controls, but no effects of acute exercise on memory. In the OFT, runners traveled less distance and spent more time grooming than controls. DSP‐4 did not attenuate the effects of exercise. A single bout of exercise increases Bdnf IV mRNA in an intensity‐dependent manner; however, high‐intensity running reduces exploratory behavior in C57BL/6J mice. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? A positive association between telomere length and exercise training has been shown in cardiac tissue of mice. It is currently unknown how each bout of exercise influences telomere-length-regulating proteins. We sought to determine how a bout of exercise altered the expression of telomere-length-regulating genes and a related signalling pathway in cardiac tissue of mice., What is the main finding and its importance? Acute exercise altered the expression of telomere-length-regulating genes in cardiac tissue and might be related to altered mitogen-activated protein kinase signalling. These findings are important in understanding how exercise provides a cardioprotective phenotype with ageing., Age is the greatest risk factor for cardiovascular disease. Telomere length is shorter in the hearts of aged mice compared with young mice, and short telomere length has been associated with an increased risk of cardiovascular disease. One year of voluntary wheel-running exercise attenuates the age-associated loss of telomere length and results in altered gene expression of telomere-length-maintaining and genome-stabilizing proteins in heart tissue of mice. Understanding the early adaptive response of the heart to an endurance exercise bout is paramount to understanding the impact of endurance exercise on heart tissue and cells. To this end, we studied mice before (BL), immediately after (TP1) and 1 h after a treadmill running bout (TP2). We measured the changes in expression of telomere-related genes (shelterin components), DNA-damage-sensing ( p53 and Chk2) and DNA-repair genes ( Ku70 and Ku80) and mitogen-activated protein kinase (MAPK) signalling. The TP1 animals had increased TRF1 and TRF2 protein and mRNA levels, greater expression of DNA-repair and -response genes ( Chk2 and Ku80) and greater protein content of phosphorylated p38 MAPK compared with both BL and TP2 animals. These data provide insights into how physiological stressors remodel the heart tissue and how an early adaptive response mediated by exercise may be maintaining telomere length and/or stabilizing the heart genome through the upregulation of telomere-protective genes. [ABSTRACT FROM AUTHOR]

This review of the exercise genomics literature encompasses the highest-quality articles published in 2015 across seven broad topics: physical activity behavior, muscular strength and power, cardiorespiratory fitness and endurance performance, body weight and adiposity, insulin and glucose metabolism, lipid and lipoprotein metabolism, and hemodynamic traits. One study used a quantitative trait locus for wheel running in mice to identify single nucleotide polymorphisms (SNPs) in humans associated with physical activity levels. Two studies examined the association of candidate gene ACTN3 R577X genotype on muscular performance. Several studies examined gene--physical activity interactions on cardiometabolic traits. One study showed that physical inactivity exacerbated the body mass index (BMI)--increasing effect of an FTO SNP but only in individuals of European ancestry, whereas another showed that high-density lipoprotein cholesterol (HDL-C) SNPs from genome-wide association studies exerted a smaller effect in active individuals. Increased levels of moderate-to-vigorous--intensity physical activity were associated with higher Matsuda insulin sensitivity index in PPARG Ala12 carriers but not Pro12 homozygotes. One study combined genome-wide and transcriptome-wide profiling to identify genes and SNPs associated with the response of triglycerides (TG) to exercise training. The genome-wide association study results showed that four SNPs accounted for all of the heritability of ΔTG, whereas the baseline expression of 11 genes predicted 27% of ΔTG. A composite SNP score based on the top eight SNPs derived from the genomic and transcriptomic analyses was the strongest predictor of $TG, explaining 14% of the variance. The review concludes with a discussion of a conceptual framework defining some of the critical conditions for exercise genomics studies and highlights the importance of the recently launched National Institutes of Health Common Fund program titled "Molecular Transducers of Physical Activity in Humans." [ABSTRACT FROM AUTHOR]

The beneficial effects of physical activity on brain health (synaptogenesis, neurogenesis, enhanced synaptic plasticity, improved learning and memory) appear to be mediated through changes in region-specific expression of neurotrophins, transcription factors, and postsynaptic receptors, though investigations of sex differences in response to long-term voluntary wheel running are limited. Purpose To examine the effect of five months of voluntary wheel running on hippocampal mRNA and protein expression of factors critical for exercise-induced structural and functional plasticity in male and female adult mice. Methods At 8 weeks of age, male and female C57BL/6 mice were individually housed with (PA; n = 20; 10 male) or without (SED; n = 20; 10 male) access to a computer monitored voluntary running wheel. At 28 weeks, all mice were sacrificed and hippocampi removed. Total RNA was isolated from the hippocampus and expression of total Bdnf , Bdnf transcript IV, tPA , Pgc-1a , GluR1 , NR2A , and NR2B were assessed with quantitative RT-PCR and total and mature Bdnf protein were assessed with ELISA. Results We found significantly higher Bdnf IV mRNA expression in PA males (p = 0.03) and females (p = 0.03) compared to SED animals. Total Bdnf mRNA expression was significantly greater in PA males compared to SED males (p = 0.01), but there was no difference in females. Similarly, we observed significantly higher mature Bdnf protein in PA males compared to SED males (p = 0.04), but not in females. Conclusion These findings indicate that the impact of long-term voluntary wheel running on transcriptional and post-translational regulation of Bdnf may be sex-dependent, though the activity-dependent Bdnf IV transcript is sensitive to exercise independent of sex. [ABSTRACT FROM AUTHOR]

This is the annual review of the exercise genomics literature in which we report on the highest quality papers published in 2014. We identified a number of noteworthy papers across a number of fields. In 70-89 yr olds, only 19% of angiotensin-converting enzyme (ACE) II homozygotes exhibited significant improvement in gait speed in response to a yearlong physical activity program compared to 30% of ACE D-allele carriers. New studies continue to support the notion that the genetic susceptibility to obesity, as evidenced by a genomic risk score (GRS; based on multiple single nucleotide polymorphisms), is attenuated by 40%-50% in individuals who are physically active, compared to those who are sedentary. One study reported that the polygenic risk for hypertriglyceridemia was reduced by 30%-40% in individuals with high cardiorespiratory fitness. One report showed that there was a significant interaction of a type 2 diabetes GRS with physical activity, with active individuals having the lowest risk of developing diabetes. The protective effect of physical activity was most pronounced in the low GRS tertile (hazard ratio, 0.82). The interaction observed with the diabetes GRS seemed to be dependent on a genetic susceptibility to insulin resistance and not insulin secretion. A significant interaction between PPARα sequence variants and physical activity levels on cardiometabolic risk was observed, with higher activity levels associated with lower risk only in carriers of specific genotypes and haplotypes. The review concludes with a discussion of the importance of replication studies when very large population or intervention discovery studies are not feasible or are cost prohibitive. [ABSTRACT FROM AUTHOR]

Aging phenotypes are dictated by myriad cellular changes including telomere shortening. In most tissues, telomere shortening is accelerated during replication if unrepaired oxidative damage to telomere sequences is present. However, the effect of reactive oxygen species exposure on skeletal muscle telomeres is unknown. We sought to determine if oxidative stress shortens telomeres in isolated adult rodent skeletal muscle fibers. Flexor digitorum brevis muscles were dissected from male mice (C57BL/6, long telomere and CAST/Ei, wild-derived, short telomere) and dissociated into single fibers. Fibers were cultured at an oxygen tension of 2%–5% for 5 days in control, hydrogen peroxide (oxidant), or a combination of N-acetylcysteine (antioxidant) and oxidant containing media. Telomere length, telomerase enzyme activity, and protein content of TRF1 and TRF2 were subsequently measured. In both strains, oxidative stress resulted in significant telomere shortening in isolated skeletal muscle fibers, likely by different mechanisms. Telomerase activity was not altered by oxidative stress treatment but was significantly different between strains, with greater telomerase activity in long-telomere–bearing C57BL/6 mice. These results provide important insights into mechanisms by which oxidative stress could shorten skeletal muscle telomeres. [ABSTRACT FROM PUBLISHER]

The most significant and scientifically sound articles in exercise genomics that were published in 2013 are reviewed in this report. No article on the genetic basis of sedentary behavior or physical activity level was identified. A calcineurin- and alpha actinin-2-based mechanism has been identified as the potential molecular basis for the observed lower muscular strength and power in alpha actinin-3-deficient individuals. Although baseline muscle transcriptomic signatures were found to be associated with strength training-induced muscle hypertrophy, no predictive genomic variants could be identified as of yet. One study found no clear evidence that the inverse relation between physical activity level and incident CHD events was influenced by 58 genomic variants clustered into four genetic scores. Lower physical activity level in North American populations may be driving the apparent risk of obesity in fat mass- and obesity-associated gene (FTO)-susceptible individuals compared with more active populations. Two large studies revealed that common genetic variants associated with baseline levels of plasma HDL cholesterol and triglycerides are not clear predictors of changes induced by interventions focused on weight loss, diet, and physical activity behavior. One large study from Japan reported that a higher fitness level attenuated the arterial stiffness-promoting effect of the Ala54 allele at the fatty acid binding protein 2 locus, which is a controversial finding because previous studies have suggested that Thr54 was the risk allele. Using transcriptomics to generate genomic targets in an unbiased manner for subsequent DNA sequence variants studies appears to be a growing trend. Moreover, exercise genomics is rapidly embracing gene and pathway analysis to better define the underlying biology and provide a foundation for the study of human variation. [ABSTRACT FROM AUTHOR]

New findings What is the central question of this study? How does parental exercise training directly and/or transgenerationally affect offspring phenotypes over two generations of mice?, What is the main finding and what is its importance? We observed preliminary evidence that parental exercise training can influence health-related phenotypes (e.g. body and fat mass, muscle gene expression) in mouse offspring. These findings indicate that parental exercise may be another environmental factor (like altered nutrition) capable of influencing offspring phenotypes in adulthood., Early life and preconception environmental stimuli can affect adult health-related phenotypes. Exercise training is an environmental stimulus affecting many systems throughout the body and appears to alter offspring phenotypes. The aim of this study was to examine the influence of parental exercise training, or 'exercise ancestry', on morphological and metabolic phenotypes in two generations of mouse offspring. The F0 C57BL/6 mice were exposed to voluntary exercise (EX) or sedentary lifestyle (SED) and bred with like-exposed mates to produce an F1 generation. The F1 mice of both ancestries were sedentary and killed at 8 weeks or bred with littermates to produce an F2 generation, which was also sedentary and killed at 8 weeks. Small but broad generation- and sex-specific effects of exercise ancestry were observed for body mass, fat and muscle mass, serum insulin, glucose tolerance and muscle gene expression. The F1 EX females were lighter than F1 SED females and had lower absolute tibialis anterior and omental fat masses. Serum insulin was higher in F1 EX females compared with F1 SED females. The F2 EX females had impaired glucose tolerance compared with F2 SED females. Analysis of skeletal muscle mRNA levels revealed several generation- and sex-specific differences in mRNA levels for multiple genes, especially those related to metabolic genes (e.g. F1 EX males had lower mRNA levels of Hk2, Ppard, Ppargc1a, Adipoq and Scd1 than F1 SED males). These results provide preliminary evidence that parental exercise training can influence health-related phenotypes in mouse offspring. [ABSTRACT FROM AUTHOR]

Aging is associated with a tissue degeneration phenotype marked by a loss of tissue regenerative capacity. Regenerative capacity is dictated by environmental and genetic factors that govern the balance between damage and repair. The age-associated changes in the ability of tissues to replace lost or damaged cells is partly the cause of many age-related diseases such as Alzheimer's disease, cardiovascular disease, type II diabetes, and sarcopenia. A well-established marker of the aging process is the length of the protective cap at the ends of chromosomes, called telomeres. Telomeres shorten with each cell division and with increasing chronological age and short telomeres have been associated with a range of age-related diseases. Several studies have shown that chronic exposure to exercise (i.e., exercise training) is associated with telomere length maintenance; however, recent evidence points out several controversial issues concerning tissue-specific telomere length responses. The goals of the review are to familiarize the reader with the current telomere dogma, review the literature exploring the interactions of exercise with telomere phenotypes, discuss the mechanistic research relating telomere dynamics to exercise stimuli, and finally propose future directions for work related to telomeres and physiological stress. [ABSTRACT FROM AUTHOR]

Reviews of several articles on exercise genomics are presented which includes the reports "Exercise and Diet Affect Quantitative Trait Loci for Body Weight and Composition Traits in an Advanced Intercross Population of Mice, by L. J. Leamy, S. A. Kelly, K. Hua, and D. Pomp in a 2012 issue of the journal "Physiological Genomics," "Variation in the Uncoupling Protein 2 and 3 Genes and Human Performance," by S. S. Dhamrait, A. G. Williams, and S. H. Day et al. in a 2012 issue of the "Journal of Applied Physiology," and "Knock-in Mice for the R50X Mutation in the PYGM Gene Present With McArdle Disease," by G. Nogales-Gadea, T. Pinos, and A. Lucia et al. in a 2012 issue of the journal "Brain."

We evaluated the impact of long-term exercise on telomere dynamics in wild-derived short telomere mice (CAST/Ei) over 1 year. We observed significant telomere shortening in liver and cardiac tissues in sedentary 1-year-old mice compared with young (8 weeks) baseline mice that were attenuated in exercised 1-year-old animals. In contrast, skeletal muscle exhibited significant telomere shortening in exercise mice compared with sedentary and young mice. Telomerase enzyme activity was increased in skeletal muscle of exercise compared with sedentary animals but was similar in cardiac and liver tissues. We observed significant age-related decreases in expression of telomere-related genes that were attenuated by exercise in cardiac and skeletal muscle but not liver. Protein content of TRF1 was significantly increased in plantaris muscle with age. In summary, long-term exercise altered telomere dynamics, slowing age-related decreases in telomere length in cardiac and liver tissue but contributing to shortening in exercised skeletal muscle. [ABSTRACT FROM PUBLISHER]

Protein kinase B (Akt) is a regulator Of insulin-stimulated glucose transport encoded by the AKT1 gene. Haplotypes of the AKT1 gene containing the G-allele at the G205T haplotype tag polymorphism are associated with higher Akt protein expression in vitro. Therefore, we hypothesized that older, Overweight or obese men and women with the GG genotype at the G205T polymorphism would have higher insulin-stimulated glucose utilization (M) as well as lower plasma glucose and insulin responses to an oral glucose tolerance test (OGTT). Sedentary, non-diabetic men (n=12) and women (n=43), 50-77 years of age, underwent hyperinsulinemic-euglycemic clamps (3-hr, 80 mU/m²/min) and OGTTs. AKT1 G205T genotype was determined by the TaqMan allelic discrimination assay. ANCOVA was used to test for differences between genotype groups, with age and sex used as covariates where appropriate. Subjects in different genotype groups were of similar age (60.9 ± 0.9 yrs), weight (88.7 ± 2.2 kg), and BMI (32.9 ± 0.7 kg/m²). Plasma glucose levels during the OGTT did not differ by genotype group. Subjects with GG genotype (n=32) had higher insulin sensitivity than T-allele carriers (n=23: GT and TT genotypes) as evidenced by: higher M during a hyperinsulinemic-euglycemic clamp (6.9 ± 0.3 vs. 5.8 ± 0.4 mg/kg/min, p=0.01); higher ISI[sub M] (3.9 ± 0.3 vs. 2.9 ± 0.3, p=0.01); lower HOMA-IR (2.4 ± 0.2 vs. 3.5 ± 0.5, p=0.02); and lower insulin area under the curve during an OGTT (49788 ± 2947 vs. 68606 ± 8611 pmol/L/120min, p=0.02). These results suggest that the AKT1 haplotype indicated by the presence of the G-allele at the AKT1 G205T polymorphism is associated with increased insulin sensitivity in older, overweight and obese, non-diabetic, older individuals. Therefore, variation within the AKT1 gene may impact insulin-stimulated glucose transport and may be useful for identifying individuals with a predisposition for insulin resistance and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Testosterone (T) has an anabolic effect on skeletal muscle and is believed to exert its local effects via the androgen receptor (AR). The AR harbors a polymorphic stretch of glutamine repeats demonstrated to inversely affect receptor transcriptional activity in prostate and kidney cells. The effects of AR glutamine repeat length on skeletal muscle are unknown. In this study we examined the effect of AR CAG repeat length on AR function in C2C12 cells. AR expression vectors harboring 14, 24, and 33 CAG repeats were used to assess AR transcriptional activity. C2C12 cell proliferation, differentiation, gene expression, myotube formation, and myonuclear fusion index were assessed. Transcriptional activity increased with increasing repeat length and in response to testosterone (AR14 = 3.91 ± 0.26, AR24 = 25.21 ± 1.72, AR33 = 36.08 ± 3.22 relative light units; P < 0.001). Ligand activation was increased for AR33 (2.10 ± 0.04) compared with AR14 (1.54 ± 0.09) and AR24 (1.57 ± 0.05, P < 0.001). AR mRNA expression was elevated in each stably transfected line. AR33 cell proliferation (20,512.3 ± 1,024.0) was decreased vs. AR14 (27,604.17 ± 1,425.3; P < 0.001) after 72 h. Decreased CK activity in AR14 cells (54.9 ± 2.9 units/μg protein) in comparison to AR33 (70.8 ± 8.1) (P < 0.05) was noted. The myonuclear fusion index was lower for AR14 (15.21 ± 3.24%) and AR33 (9.97 ± 3.14%) in comparison to WT (35.07 ± 5.60%, P < 0.001). AR14 and AR33 cells also displayed atypical myotube morphology. RT-PCR revealed genotype differences in myostatin and myogenin expression. We conclude that AR polyglutamine repeat length is directly associated with transcriptional activity and alters the growth and development of C2C12 cells. This polymorphism may contribute to the heritability of muscle mass in humans. [ABSTRACT FROM AUTHOR]

The article presents a review of literature on exercise genomics. It discusses 2010 articles focusing on physical activity, endurance performance, muscular strength and power, diposity, hemodynamic traits, and glucose and insulin metabolism. It cites that J. R. Ruiz and colleagues' study of the potential for naming a "power-oriented polygenic" enables the use of a "total genotype score" (TGS) approach. N. T. Jenkins and colleagues investigated the link of common sequence variants in the perilipin (PLIN) gene with aerobic fitness, body fatness, and related risk factors of cardiovascular disease. It mentions that a major strength of J. J. Mann and colleagues' study of hemodynamic traits is the sample size of men. It concludes that there is an urgent need for studies with large sample sizes.

As part of the insulin signalling pathway, Akt influences growth and metabolism. The AKT1 gene G205T (rs1130214) polymorphism has potential functional effects. Thus, we determined whether the G205T polymorphism influences metabolic variables and their responses to aerobic exercise training. Following dietary stabilization, healthy, sedentary, 50- to 75-year-old Caucasian men ( n= 51) and women ( n= 58) underwent 6 months of aerobic exercise training. Before and after completing the intervention, dual-energy X-ray absorptiometry was used to measure percentage body fat, computed tomography to measure visceral and subcutaneous fat, and oral glucose tolerance testing to measure glucose total area under the curve (AUC), insulin AUC and insulin sensitivity. Taqman assay was used to determine AKT1 G205T genotypes. At baseline, men with the GG genotype ( n= 29) had lower maximal oxygen consumption values ( P= 0.026) and higher percentage body fat ( P= 0.046), subcutaneous fat ( P= 0.021) and insulin AUC ( P= 0.003) values than T allele carriers ( n= 22). Despite their rather disadvantageous starting values, men with the GG genotype seemed to respond to exercise training more robustly than men with the T allele, highlighted by significantly greater fold change improvements in insulin AUC ( P= 0.012) and glucose AUC ( P= 0.035). Although the GG group also significantly improved with training, the change in was not as great as that of the T allele carriers ( P= 0.037). In contrast, after accounting for hormone replacement therapy use, none of the variables differed in the women at baseline. As a result of exercise training, women with the T allele ( n= 20) had greater fold change improvements in fasting glucose ( P= 0.011), glucose AUC ( P= 0.017) and insulin sensitivity ( P= 0.044) than GG genotype women ( n= 38). Our results suggest that the AKT1 G205T polymorphism influences metabolic variables and their responses to aerobic exercise training in older, previously sedentary individuals. [ABSTRACT FROM AUTHOR]

Muscle strength is important in functional activities of daily living and the prevention of common pathologies. We describe the two-staged fine mapping of a previously identified linkage peak for knee strength on chr12q12-14. First, 209 tagSNPs in/around 74 prioritized genes were genotyped in 500 Caucasian brothers from the Leuven Genes for Muscular Strength study (LGfMS). Combined linkage and family-based association analyses identified activin receptor 1B (ACVR1B) and inhibin β C (INHBC), part of the transforming growth factor β pathway regulating myostatin - a negative regulator of muscle mass - signaling, for follow-up. Second, 33 SNPs, selected in these genes based on their likelihood to functionally affect gene expression/function, were genotyped in an extended sample of 536 LGfMS siblings. Strong associations between ACVR1B genotypes and knee muscle strength (P-values up to 0.00002) were present. Of particular interest was the association with rs2854464, located in a putative miR-24-binding site, as miR-24 was implicated in the inhibition of skeletal muscle differentiation. Rs2854464 AA individuals were ∼2% stronger than G-allele carriers. The strength increasing effect of the A-allele was also observed in an independent replication sample (n=266) selected from the Baltimore Longitudinal Study of Aging and a Flemish Policy Research Centre Sport, Physical Activity and Health study. However, no genotype-related difference in ACVR1B mRNA expression in quadriceps muscle was observed. In conclusion, we applied a two-stage fine mapping approach, and are the first to identify and partially replicate genetic variants in the ACVR1B gene that account for genetic variation in human muscle strength. [ABSTRACT FROM AUTHOR]

The article provides information on the research advances which was reported in 2006 and 2007 regarding the human gene map for physical performance and health-related fitness phenotypes. It provides a brief discussion on the nature of the evidence and on what to look for in assessing human genetic studies related to fitness and performance. It discusses the reviewed findings of the related studies published in 2006 and 2007, which are added to the appropriate tables that are designed to become the cumulative summary of all publications with positive genetic associations available for a given phenotype and study design.

Objective. The purpose of this study was to examine the association of the alpha-actinin-3 (ACTN3) R577X polymorphism on muscle function and physical performance in older adults. Methods. We measured knee extensor torque, midthigh muscle cross-sectional area, muscle quality, short physical performance battery score, and 400-meter walk time at baseline and after 5 years in white older adults aged 70-79 years in the Health, Aging and Body Composition Study cohort (n = 1367). Incident persistent lower extremity limitation (PLL) over 5 years was additionally assessed. We also examined white men in the Osteoporotic Fractures in Men Study, a longitudinal, observational cohort (n = 1152) of men 65 years old or older as a validation cohort for certain phenotypes. Results. There were no significant differences between genotype groups in men or women for adjusted baseline phenotypes. Male X-homozygotes had a significantly greater adjusted 5-year increase in their 400-meter walk time compared to R-homozygotes and heterozygotes (p = .03). In women, X-homozygotes had a ∼-35% greater risk of incident PLL compared to R-homozygotes (hazard ratio = 0.65, 95% confidence interval = 0.44-0.94). There were no other significant associations between any of the phenotypes and ACTN3 genotype with aging in either cohort. Conclusions. The ACTN3 polymorphism may influence declines in certain measures of physical performance with aging in older white adults, based on longitudinal assessments. However, the influence of the ACTN3 R577X polymorphism does not appear to have a strong effect on skeletal muscle-related phenotypes based on the strength and consistency of the associations and lack of replication with regard to specific phenotypes. [ABSTRACT FROM AUTHOR]

The article cites a study which examines the relationship of exercise energy expenditure (EEE) with both telomere length and telomerase activity. The study involves 69 participants 50-70 year who were assessed for weekly EEE level using the Yale Physical Activity Survey. It is revealed that the second EEE quartertile exhibited significantly longer telomere lengths than both the first and fourth EEE quartertiles, but was not different from the third quartertile. It is concluded that moderate physical activity levels provides a protective effect on peripheral blood mononuclear cells (PBMC) telomere length compared with both low and high EEE levels.

Abstract: Performance on the Sternberg working memory task, and MEG cortical response on a variation of the Sternberg task were examined in middle-aged carriers and non-carriers of the APOE ɛ4 allele. Physical activity was also assessed to examine whether exercise level modifies the relationship between APOE genotype and neurocognitive function. Regression revealed that high physical activity was associated with faster RT in the six- and eight-letter conditions of the Sternberg in ɛ4 carriers, but not in the non-carriers after controlling for age, gender, and education (N =54). Furthermore, the MEG analysis revealed that sedentary ɛ4 carriers exhibited lower right temporal lobe activation on matching probe trials relative to high-active ɛ4 carriers, while physical activity did not distinguish non-carriers (N =23). The M170 peak was identified as a potential marker for pre-clinical decline as ɛ4 carriers exhibited longer M170 latency, and highly physically active participants exhibited greater M170 amplitude to matching probe trials. [Copyright &y& Elsevier]

In endothelial cells, NF-κB is an important intracellular signaling molecule by which changes in wall shear stress are transduced into the nucleus to initiate downstream endothelial nitric oxide synthase (NOS3) gene expression. We investigated whether NF-κ light-chain gene enhancer in B cells 1 (NFKB1) promoter polymorphism (-94NFKB1 I/D, where I is the insertion allele and D is the deletion allele) was associated with 1) NOS3 gene expression in endothelial cells under physiological levels of unidirectional laminar shear stress (LSS) and 2) endothelial function in prehypertensive and stage 1 hypertensive individuals before and after a 6-too supervised endurance exercise intervention. Competitive EMSAs revealed that proteins present in the nuclei of endothelial cells preferentially bound to the I allele NFKB1 promoter compared with the D allele. Reporter gene assays showed that the I allele promoter had significantly higher activity than the D allele. In agreement with these observations, homozygous II genotype cells had higher p50 expression levels than homozygous DD genotype cells. Cells with the homozygous II genotype showed a greater increase in NOS3 protein expression than did homozygous DD genotype cells under LSS. Functional experiments on volunteers confirmed higher baseline reactive hyperemic forearm blood flow, and, furthermore, the subgroup analysis revealed that DD homozygotes were significantly less prevalent in the exercise responder group compared with II and ID genotypes. We conclude that the -94NFKB1 I/D promoter variation contributes to the modulation of vascular function and adaptability to exercise-induced flow shear stress, most likely due to differences in NFKB1 gene transactivity. [ABSTRACT FROM AUTHOR]

Background. The alpha-actinin-3 (ACTN3) R577X polymorphism has been associated with muscle power performance in cross-sectional studies. Methods. We examined baseline knee extensor concentric peak power (PP) and PP change with ∼10 weeks of unilateral knee extensor strength training (ST) using air-powered resistance machines in 71 older men (65 [standard deviation = 81] years) and 86 older women (64 [standard deviation = 9] years). Results. At baseline in women, the XX genotype group had an absolute (same resistance) PP that was higher than the RR (p = .005) and RX genotype groups (p = .02). The women XX group also had a relative (70% of one-repetition maximum [1 -RM]) PP that was higher than that in the RR (p = .002) and RX groups (p = .008). No differences in baseline absolute or relative PP were observed between ACTN3 genotype groups in men. In men, absolute PP change with ST in the RR (n = 16) group approached a significantly higher value than in the XX group (n = 9; p = .07). In women, relative PP change with ST in the RR group (n = 16) was higher than in the XX group (n = 17; p = .02). Conclusions. The results indicate that the ACTN3 R577X polymorphism influences the response of quadriceps muscle power to ST in older adults. [ABSTRACT FROM AUTHOR]

The article reports on the human gene map for physical performance and health-related fitness phenotypes. This research is based on peer-reviewed papers published by the end of 2005. The markers and genes with evidence of connectivity with a performance or fitness phenotype in active or sedentary people, in adaptation to exercise, or for training-induced alterations are placed on the genetic map of all autosomes and the X chromosome. In the 2005 gene map for physical performance and health-connected phenotypes, there are 165 autosomal gene entries and QTL, and five others on the X chromosome.

In its role as an endothelial cell proliferation and migration factor, vascular endothelial growth factor (VEGF) can affect peripheral circulation and therefore impact maximal oxygen consumption (V̇o2 max). Because of the role of VEGF, and because variation in the VEGF gene has the ability to alter VEGF gene expression and VEGF protein level, we hypothesized that VEGF gene polymorphisms are related to VEGF gene expression in human myoblasts and V̇o2 max before and after aerobic exercise training. We analyzed the effects of the VEGF -2578/ -1154/-634 promoter region haplotype on VEGF gene expression by using a luciferase reporter assay in cultured human myoblasts and found that the AAG and CGC haplotypes resulted in significantly higher hypoxia-stimulated VEGF gene expression than the AGG and CGG haplotypes. Consistent with these results, we found that individuals with at least one copy of the AAG or CGC haplotype had higher V̇o2 max before and after aerobic exercise training than did subjects with only the AGG and/or CGG haplotype. In conclusion, we found that VEGF-2578/-1154/-634 haplotype impacts VEGF gene expression in human myoblasts and is associated with V̇o2 max. These results have potential implications for aerobic exercise training and may prove relevant in the study of pathological conditions that can be affected by angiogenesis, such as coronary artery disease and peripheral artery disease. [ABSTRACT FROM AUTHOR]

To determine the influence of the vitamin D receptor (VDR) gene FokI and BsmI genotype on bone mineral density response to two exercise training modalities, 206 healthy men and women (50–81 years old) were studied before and after ∼5–6 months of either aerobic exercise training (AT) or strength training (ST). A totla of 123 subjects completed AT (51 men, 72 women) and 83 subjects completed ST (40 men, 43 women). DNA was extracted from blood samples of all subjects and genotyping was performed at the VDR FokI and BsmI locus to determine its association to training response. Total body, greater trochanter and femoral neck bone mineral density (BMD) were measured before and after both training programmes using dual-energy X-ray absorptiometry. VDR BsmI genotype was not significantly related to BMD at baseline or after ST or AT. However, VDR FokI genotype was significantly related to ST- but not AT-induced changes in femoral neck BMD ( P < 0.05). The heterozygotes (Ff) in the ST group approached a significantly greater increase in femoral neck BMD ( P= 0.058) compared to f homozygotes. There were no significant genotype relationships in the AT group. These data indicate that VDR FokI genotype may influence femoral neck BMD response to ST, but not AT. [ABSTRACT FROM AUTHOR]

To determine the influence of angiotensinogen (AGT) A–20C, M235 T, and angiotensin II type 1 receptor (AGTR1) A1166C genotypes on resting blood pressure (BP) response to strength training (ST) in older men and women.Prospective intervention study with retrospective genotyping.University of Maryland Exercise Physiology Laboratory.Seventy sedentary, healthy older men (n=34) and women (n=36).Approximately 23 weeks of ST performed 3 days per week.Resting BP was measured on six separate occasions before and after ST for each subject. AGT and AGTR1 genotyping was performed retrospectively from each subject's genomic deoxyribonucleic acid.Systolic BP decreased in C-allele carriers at the AGT A–20C locus with ST (122±1 to 116±2 mmHg,P<.05), which was significantly greater than the decrease in the A homozygotes (126±1 to 123±1 mmHg,P<.05). At the AGTR1 A1166C locus, diastolic BP decreased to a greater extent in the C-allele carriers (76±1 to 70±2 mmHg,P<.05) than in the A homozygotes (75±1 to 72±1 mmHg,P<.05).The AGT A–20C and AGTR1 A1166C genotypes may influence resting BP response to ST, such that C-allele carriers at each of these loci reduce their resting BP in response to ST to a greater extent than A homozygotes. [ABSTRACT FROM AUTHOR]

Exogenous ciliary neurotrophic factor (CNTF) administration causes significant weight loss in both humans and animal models, but the effects of endogenous CNTF and the CNTF null allele on body composition are not fully understood. A recent study in a European cohort demonstrated a significantly higher body weight and body mass index (BMI) in older males homozygous for the CNTF null allele (A/A genotype). We sought to replicate these findings in three cohorts: the Baltimore Longitudinal Study on Aging (BLSA) consisting of 422 adult men and women (19-90 years); the Study of Osteoporotic Risk in Men (STORM) consisting of 333 older men (50-84 years); and a third sample obtained by combining older males aged 59-73 years from the BLSA and STORM cohorts (n=286). In contrast to the European study, we were unable to detect a significant association between CNTF genotype and body weight in the BLSA (P=0.49), the STORM (P=0.28), or the combined samples (P=0.72). There was also no significant association observed between CNTF genotype and BMI in the BLSA (P=0.59), the STORM (P=0.34) or the combined (P=0.56) samples. In addition, we were unable to detect a significant association between CNTF genotype and total body fat (P=0.95) or fat-free mass (P=0.86) in the BLSA cohort. Our results do not support an effect of the CNTF null allele on body composition, contrary to previous findings.European Journal of Human Genetics (2004) 12, 372-376. doi:10.1038/sj.ejhg.5201159 Published online 28 January 2004 [ABSTRACT FROM AUTHOR]

PURPOSE: Tumor necrosis factor alpha (TNFa) has been implicated in the regulation of muscle protein metabolism. A promoter polymorphism in the TNFa gene (TNFa -308 G/A) has been associated with higher production of TNFa. In this study, the relationship between TNFa -308G/A genotype and muscle mass was investigated in adult individuals. METHODS: 1095 participants of Baltimore Longitudinal Study of Aging (BLSA) (age range: 19 to 97 yr, 529 females and 566 males) were genotyped for TNFa -308G/A. Skeletal muscle mass (measured by DXA) was compared among different genotype groups. Age, gender, race and height were accounted for as confounding factors. RESULTS: TNFa genotype was significantly associated with both total body lean mass (LM) (p<0.0001) and appendicular skeletal muscle mass (ASMM) (p=0.0021). The AA genotype group (n=28) had higher muscle mass than the GA and GG groups (n=306 and 760) (LM: 68.1±2.2 vs. 56.2±0.6 and 56.6±0.4kg, p<0.0001; ASMM: 29.4 ±1.3 vs. 24.1±0.4 and 24.3±0.3kg, p=0.0006). Due to limitation in sample sizes; further analysis in subgroups only showed significant associations between TNFa genotype and muscle mass in white males (LM: P<0.0001; ASMM: p=0.0016). CONCLUSIONS: TNFa -308G/A genotype was significantly associated with muscle mass, with AA homozygotes having higher muscle mass than G allele carriers in healthy individuals. [ABSTRACT FROM AUTHOR]

PURPOSE: To examine genetic variation and haplotype structure in the Activin RIIB gene (ACVR2B), the primary receptor for myostatin signaling, and identify associations with skeletal muscle related phenotypes. METHODS: Three hundred and fifteen Caucasian males and 278 Caucasian females aged 19-90 years from the Baltimore Longitudinal Study of Aging were genotyped (rs# 2268757) to determine respective ACVR2B haplotype groups. Whole-body soft tissue composition was measured by dual-energy X-ray absorptiometry. Quadriceps peak torque (strength) was measured using an isokinetic dynamometer. RESULTS: Women carriers of ACVR2B haplotype group 1 exhibited significantly less quadriceps muscle strength (shortening phase) than women homozygous for haplotype group 2 (109.2 ± 1.9 vs 118.6 ± 4.1 N·m, 0.52 rad/sec, respectively, p < 0.05). No significant association was observed in men. CONCLUSION: The results indicate that haplotype structure at the ACVR2B gene may contribute to inter-individual variation in skeletal muscle mass and strength, though the data indicate a sex-specific relationship. [ABSTRACT FROM AUTHOR]