Regular aerobic physical activity (PA) increases exercise capacity and physical fitness (PF), which can lead to many health benefits. Accurate quantification of PA and PF becomes essential in terms of health outcome and effectiveness of intervention programmes. In this manuscript we present a review regarding the assessment of physical activity and fitness. Three types of PA assessment methods can be distinguished: criterion methods, objective methods and subjective methods. Criterion methods like doubly labelled water, indirect calorimetry and direct observation are the most reliable and valid measurements against which all other PA assessments methods should be validated, but they also hold important drawbacks. Objective PA assessment methods include activity monitors (pedometers and accelerometers) and heart rate monitoring. Finally, questionnaires and activity diaries are considered subjective methods. For the assessment of PF, we distinguish field tests and laboratory tests. The Eurofit for Adults is a test battery that is designed to assess health-related fitness of individuals, communities, sub-populations and populations. It is mainly used for evaluating the morphological component, the muscular component, the motor component and the cardio-respiratory component. In the laboratory, exercise capacity is preferentially assessed through maximal incremental exercise testing. Cardio-pulmonary exercise testing is a well-established procedure that provides a wealth of clinically diagnostic and prognostic information. The peak oxygen uptake is the gold standard in the assessment of exercise tolerance. When maximal exercise is contraindicated or not achievable, the VAT or the submaximal slopes provide reasonable alternatives.

Regular aerobic physical activity (PA) increases exercise capacity and physical fitness (PF), which can lead to many health benefits. Accurate quantification of PA and PF becomes essential in terms of health outcome and effectiveness of intervention programmes. In this manuscript we present a review regarding the assessment of physical activity and fitness. Three types of PA assessment methods can be distinguished: criterion methods, objective methods and subjective methods. Criterion methods like doubly labelled water, indirect calorimetry and direct observation are the most reliable and valid measurements against which all other PA assessments methods should be validated, but they also hold important drawbacks. Objective PA assessment methods include activity monitors (pedometers and accelerometers) and heart rate monitoring. Finally, questionnaires and activity diaries are considered subjective methods. For the assessment of PF, we distinguish field tests and laboratory tests. The Eurofit for Adults is a test battery that is designed to assess health-related fitness of individuals, communities, sub-populations and populations. It is mainly used for evaluating the morphological component, the muscular component, the motor component and the cardio-respiratory component. In the laboratory, exercise capacity is preferentially assessed through maximal incremental exercise testing. Cardio-pulmonary exercise testing is a well-established procedure that provides a wealth of clinically diagnostic and prognostic information. The peak oxygen uptake is the gold standard in the assessment of exercise tolerance. When maximal exercise is contraindicated or not achievable, the VAT or the submaximal slopes provide reasonable alternatives.

This study explores the associations between polymorphisms in two candidate genes-myostatin gene (MSTN or GDF8) and angiotensin-converting enzyme (ACE) gene-with interindividual differences in human muscle mass and strength responses to strength training. The MSTN AluI A55T (exon 1), BanII K153R, TaqI E164 K and BstNI P198A (all in exon 2) markers and the ACE insertion (I)/deletion (D) polymorphism were typed in 57 males [22.4 (3.7) years] who participated in a 10-week, high-resistance training program for the elbow flexors. Maximal strength, and maximal isometric and concentric elbow flexor torques were measured at baseline and after training. Information on muscle cross-sectional area of the upper arm was obtained by computer tomography scans. Only one individual was heterozygous for the MSTN BanII K153R variant. No allelic variant was detected at the other MSTN sites in this population. For the ACE I/D polymorphism, no evidence was found for an association of the D or I allele with baseline strength, isometric and concentric torque or arm muscle cross-sectional area [analysis of covariance (ANCOVA) 0.25< P<0.97]. Responses to the strength-training program were not associated with the ACE I/D genotype (ANCOVA 0.057< P<0.70). Borderline significance was found for larger strength gains in dynamic flexion torques for I/I genotypes. This study therefore does not support the hypothesis that an increased muscle fiber hypertrophic effect of strength training is present in D-allele carriers.

This study was the first to explore the potential role of the myostatin (GDF8) pathway in relation to muscle strength and estimated muscle cross-sectional area in humans using linkage analysis with a candidate gene approach. In young male sibs (n = 329) 11 polymorphic markers in or near 10 candidate genes from the myostatin pathway were genotyped. Muscle mass was estimated by anthropometric measurements, and maximal knee strength was evaluated using isokinetic dynamometers (Cybex NORM). Single-point nonparametric variance components and linear quantitative trait locus regression linkage analysis methods were used. Linkage patterns were observed between knee extension and flexion peak torque with markers D2S118 (GDF8), D6S1051 (CDKN1A), and D11S4138 (MYOD1), and a maximum LOD score of 2.63 (P = 0.0002) was observed with D2S118. The ratios of peak torque over muscle and bone area of the midthigh of the lower contraction velocity (60 degrees/s) showed more frequently significant LOD scores than the torques at high velocity (240 degrees/s). Although myostatin is physiologically more related to muscle mass through possible effects of hyperplasia and hypertrophy than it is to strength, only two estimated muscle cross-sectional areas were marginally linked (LOD 1.06 and 1.07, P = 0.01) with marker D2S118 near GDF8 (2q32.2). The present results gave suggestive evidence that the myostatin pathway might be important for strength phenotypes, and GDF8, CDKN1A, and MYOD1 are potential candidate regions for a further and denser mapping with respect to these phenotypes.

The purpose of this study was to estimate the genetic and environmental contribution to variation in skeletal muscle mass and strength. In addition, important determinants were analyzed by stepwise multiple regression. In a large (N = 748) sibling pair sample of young brothers, ages 24.3 +/- 4.5 years, upper-limit heritabilities (t2) were estimated as a proportion of genetic and shared environmental variability over total phenotypic variability by the variance components method in QTDT. Maximal isometric strength measures of knee, trunk, and elbow had higher t2 (82 to 96%) than concentric strength (63 to 87%) on Cybex isokinetic dynamometers. Indicators of muscle mass revealed very high transmissions (>90%) whereas t2 was lower for adiposity (<70%). Stepwise regression showed that fat-free mass was the primary determinant in knee and trunk strength (partial explained variance, R2 = 33-45%), but a local muscularity estimate (forearm circumference) was the main covariable for elbow strength (partial R2 = 18-39%). In this sample neither age nor physical activity, measured by the sport index of Baecke, appeared to be an important determinant of muscle mass or strength. These results show that maximal muscle strength and mass are highly transmissible and that muscle mass is the primary determinant of muscle strength.

This study reports the results of a multipoint linkage study that aims to unravel the genetic basis of muscle strength and muscle mass in humans. Myostatin (GDF8) is known to be a strong inhibitor of muscle growth in animals. However, studies examining human myostatin polymorphisms are rare and are limited to the GDF8 gene itself. Here, the contribution to isometric and concentric knee strength of nine key proteins involved in the myostatin pathway is studied in a nonparametric multipoint linkage analysis by means of a variance components and regression method. A sample of 367 healthy young male siblings was phenotyped on an isokinetic dynamometer and genotyped for markers of the myostatin pathway genes. Three of the loci were found significantly linked with a quantitative trait locus (QTL) for knee muscle strength. First, D13S1303 showed replication of an explorative single-point linkage study with a maximum LOD score of 2.7 (P = 0.0002). Second, maximum LOD scores of 3.4 (P = 0.00004) and 3.3 (P = 0.00005) were observed for markers D12S1042 and D12S85, respectively, at 12q12-14. Finally, marker D12S78 showed an LOD score of 2.7 at 12q22-23. We conclude that several genes involved in the myostatin pathway, but not the myostatin gene itself, are important QTLs for human muscle strength. An additional set of valuable candidate genes that were not part of the myostatin pathway was found in the chromosome 12 and 13 genomic regions.

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 b C (INHBC), part of the transforming growth factor b 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 B2% stronger than G-allele carriers. The strength increasing effect of the A-allele was also observed in an independent replication sample (n¼266) 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.

Background:Maintenance of high muscular fitness is positively related to bone health, functionality in daily life and increasing insulin sensitivity, and negatively related to falls and fractures, morbidity and mortality. Heritability of muscle strength phenotypes ranges between 31% and 95%, but little is known about the identity of the genes underlying this complex trait. As a first attempt, this genome-wide linkage study aimed to identify chromosomal regions linked to muscle and bone cross-sectional area, isometric knee flexion and extension torque, and torque–length relationship for knee flexors and extensors.Methods:In total, 283 informative male siblings (17–36 years old), belonging to 105 families, were used to conduct a genome-wide SNP-based multipoint linkage analysis.Results:The strongest evidence for linkage was found for the torque–length relationship of the knee flexors at 14q24.3 (LOD  = 4.09; p<10−5). Suggestive evidence for linkage was found at 14q32.2 (LOD  = 3.00; P = 0.005) for muscle and bone cross-sectional area, at 2p24.2 (LOD  = 2.57; p = 0.01) for isometric knee torque at 30° flexion, at 1q21.3, 2p23.3 and 18q11.2 (LOD  = 2.33, 2.69 and 2.21; p<10−4 for all) for the torque–length relationship of the knee extensors and at 18p11.31 (LOD  = 2.39; p = 0.0004) for muscle-mass adjusted isometric knee extension torque.Conclusions:We conclude that many small contributing genes rather than a few important genes are involved in causing variation in different underlying phenotypes of muscle strength. Furthermore, some overlap in promising genomic regions were identified among different strength phenotypes.