Physical activity, sedentary behaviour, and cognitive function among older adults: A bibliometric analysis from 2004 to 2024.

Because of population ageing, there will be a vast increase in the prevalence of cognitive decline and dementia. Physical activity and sedentary behaviour have been identified as modifiable lifestyle behaviours associated with these cognitive conditions. Therefore, the aim of this bibliometric analysis is to reveal the knowledge structure of the field of physical activity, sedentary behaviour, and cognitive function among older adults from 2004 to 2024, and to predict emerging research trends. A total of 1290 publications were retrieved from the Web of Science Core Collection. CiteSpace and VOSviewer were applied to conduct performance analysis, science mapping, and enrichment. T. Liu-Ambrose was the most prolific author (39 publications), and the University of British Columbia was the most prolific institution (48 publications). The USA, China, and Canada were the three most productive countries with 392, 174, and 136 publications respectively. Two research trends revealed the knowledge structure of this field, including the shift from evaluating the effectiveness of interventions on cognitive function to evaluating the effectiveness of interventions on other health-related outcomes, as well as an expansion of research on the role of physical activity and sedentary behaviour in the context of healthy ageing. Sleep, sedentary behaviour, and virtual reality may be emerging research trends and may predict directions for future research. Collectively, this bibliometric analysis provides a one-step overview of the knowledge structure in this field for researchers and other stakeholders, as well as a reference for future research.

Interrelationships among skeletal age, growth status and motor performances in female athletes 10-15 years.

BACKGROUND: Motor performances of youth are related to growth and maturity status, among other factors. AIM: To estimate the contribution of skeletal maturity status per se to the motor performances of female athletes aged 10-15 years and the mediation effects of growth status on the relationships. SUBJECTS AND METHODS: Skeletal age (TW3 RUS SA), body size, proportions, estimated fat-free mass (FFM), motor performances, training history and participation motivation were assessed in 80 non-skeletally mature female participants in several sports. Hierarchical and regression-based statistical mediation analyses were used. RESULTS: SA per se explained a maximum of 1.8% and 5.8% of the variance in motor performances of athletes aged 10-12 and 13-15 years, respectively, over and above that explained by covariates. Body size, proportions, and hours per week of training and participation motivation explained, respectively, a maximum of 40.7%, 18.8%, and 22.6% of the variance in performances. Mediation analysis indicated specific indirect effects of SA through stature and body mass, alone or in conjunction with FFM on performances. CONCLUSION: SA per se accounted for small and non-significant amounts of variance in several motor performances of female youth athletes; rather, SA influenced performances indirectly through effects on stature, body mass and estimated FFM.

Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle.

Exercise training prevents age-related decline in muscle function. Targeting epigenetic aging is a promising actionable mechanism and late-life exercise mitigates epigenetic aging in rodent muscle. Whether exercise training can decelerate, or reverse epigenetic aging in humans is unknown. Here, we performed a powerful meta-analysis of the methylome and transcriptome of an unprecedented number of human skeletal muscle samples (n = 3176). We show that: (1) individuals with higher baseline aerobic fitness have younger epigenetic and transcriptomic profiles, (2) exercise training leads to significant shifts of epigenetic and transcriptomic patterns toward a younger profile, and (3) muscle disuse "ages" the transcriptome. Higher fitness levels were associated with attenuated differential methylation and transcription during aging. Furthermore, both epigenetic and transcriptomic profiles shifted toward a younger state after exercise training interventions, while the transcriptome shifted toward an older state after forced muscle disuse. We demonstrate that exercise training targets many of the age-related transcripts and DNA methylation loci to maintain younger methylome and transcriptome profiles, specifically in genes related to muscle structure, metabolism, and mitochondrial function. Our comprehensive analysis will inform future studies aiming to identify the best combination of therapeutics and exercise regimes to optimize longevity.

Ten-year longitudinal changes in muscle power, force, and velocity in young, middle-aged, and older adults.

BACKGROUND: Maximum muscle power (Pmax ) is a biomarker of physical performance in all ages. No longitudinal studies have assessed the effects of aging on Pmax obtained from the torque-velocity (T-V) relationship, which should be considered the 'gold standard'. This study evaluated the longitudinal changes in the T-V relationship and Pmax of the knee-extensor muscles in young, middle-aged, and older adults after 10 years of follow-up. METHODS: Four hundred eighty-nine subjects (311 men and 178 women; aged 19-68 years) were tested at baseline and after a 10-year follow-up. Anthropometric data, daily protein intake, physical activity level (PAL), and knee-extension muscle function (isometric, isokinetic, and isotonic) were evaluated. A novel hybrid equation combining a linear and a hyperbolic (Hill-type) region was used to obtain the T-V relationship and Pmax of the participants, who were grouped by sex and age (young: 20-40 years; middle-aged: 40-60 years; and old: ≥60 years). Linear mixed-effect models were used to assess effects of time, sex, and age on T-V parameters, Pmax , and body mass index (BMI). Additional analyses were performed to adjust for changes in daily protein intake and PAL. RESULTS: Pmax decreased in young men (-0.6% per year; P < 0.001), middle-aged men and women (-1.1% to -1.4% per year; P < 0.001), and older men and women (-2.2% to -2.4% per year; P ≤ 0.053). These changes were mainly related to decrements in torque at Pmax at early age and to decrements in both torque and velocity at Pmax at older age. BMI increased among young and middle-aged adults (0.2% to 0.5% per year; P < 0.001), which led to greater declines in relative Pmax in those groups. S/T0 , that is, the linear slope of the T-V relationship relative to maximal torque, exhibited a significant decline over time (-0.10%T0 ·rad·s-1 per year; P < 0.001), which was significant among middle-aged men and old men and women (all P < 0.05). Annual changes in PAL index were significantly associated to annual changes in Pmax (P = 0.017), so the overall decline in Pmax was slightly attenuated in the adjusted model (-5.26 vs. -5.05 W per year; both P < 0.001). CONCLUSIONS: Pmax decreased in young, middle-aged, and older adults after a 10-year follow-up. The early declines in Pmax seemed to coincide with declines in force, whereas the progressive decline at later age was associated with declines in both force and velocity. A progressively blunted ability to produce force, especially at moderate to high movement velocities, should be considered a specific hallmark of aging.

Genetic regulation of body size and morphology in children: a twin study of 22 anthropometric traits.

BACKGROUND: Anthropometric measures show high heritability, and genetic correlations have been found between obesity-related traits. However, we lack a comprehensive analysis of the genetic background of human body morphology using detailed anthropometric measures. METHODS: Height, weight, 7 skinfold thicknesses, 7 body circumferences and 4 body diameters (skeletal breaths) were measured in 214 pairs of twin children aged 3-18 years (87 monozygotic pairs) in the Autonomous Region of Madeira, Portugal. Factor analysis (Varimax rotation) was used to analyze the underlying structure of body physique. Genetic twin modeling was used to estimate genetic and environmental contributions to the variation and co-variation of the anthropometric traits. RESULTS: Together, two factors explained 80% of the variation of all 22 anthropometric traits in boys and 73% in girls. Obesity measures (body mass index, skinfold thickness measures, as well as waist and hip circumferences) and limb circumferences loaded most strongly on the first factor, whereas height and body diameters loaded especially on the second factor. These factors as well as all anthropometric measures showed high heritability (80% or more for most of the traits), whereas the rest of the variation was explained by environmental factors not shared by co-twins. Obesity measures showed high genetic correlations (0.75-0.98). Height showed the highest genetic correlations with body diameter measures (0.58-0.76). Correlations between environmental factors not shared by co-twins were weaker than the genetic correlations but still substantial. The correlation patterns were roughly similar in boys and girls. CONCLUSIONS: Our results show high genetic correlations underlying the human body physique, suggesting that there are sets of genes widely affecting anthropometric traits. Better knowledge of these genetic variants can help to understand the development of obesity and other features of the human physique.

Polygenic Models Partially Predict Muscle Size and Strength but Not Low Muscle Mass in Older Women.

Background: Heritability explains 45-82% of muscle mass and strength variation, yet polygenic models for muscle phenotypes in older women are scarce. Therefore, the objective of the present study was to (1) assess if total genotype predisposition score (GPSTOTAL) for a set of polymorphisms differed between older women with low and high muscle mass, and (2) utilise a data-driven GPS (GPSDD) to predict the variance in muscle size and strength-related phenotypes. Methods: In three-hundred 60- to 91-year-old Caucasian women (70.7 ± 5.7 years), skeletal muscle mass, biceps brachii thickness, vastus lateralis anatomical cross-sectional area (VLACSA), hand grip strength (HGS), and elbow flexion (MVCEF) and knee extension (MVCKE) maximum voluntary contraction were measured. Participants were classified as having low muscle mass if the skeletal muscle index (SMI) < 6.76 kg/m2 or relative skeletal muscle mass (%SMMr) < 22.1%. Genotyping was completed for 24 single-nucleotide polymorphisms (SNPs). GPSTOTAL was calculated from 23 SNPs and compared between the low and high muscle mass groups. A GPSDD was performed to identify the association of SNPs with other skeletal muscle phenotypes. Results: There was no significant difference in GPSTOTAL between low and high muscle mass groups, irrespective of classification based on SMI or %SMMr. The GPSDD model, using 23 selected SNPs, revealed that 13 SNPs were associated with at least one skeletal muscle phenotype: HIF1A rs11549465 was associated with four phenotypes and, in descending number of phenotype associations, ACE rs4341 with three; PTK2 rs7460 and CNTFR rs2070802 with two; and MTHFR rs17421511, ACVR1B rs10783485, CNTF rs1800169, MTHFR rs1801131, MTHFR rs1537516, TRHR rs7832552, MSTN rs1805086, COL1A1 rs1800012, and FTO rs9939609 with one phenotype. The GPSDD with age included as a predictor variable explained 1.7% variance of biceps brachii thickness, 12.5% of VLACSA, 19.0% of HGS, 8.2% of MVCEF, and 9.6% of MVCKE. Conclusions: In older women, GPSTOTAL did not differ between low and high muscle mass groups. However, GPSDD was associated with muscle size and strength phenotypes. Further advancement of polygenic models to understand skeletal muscle function during ageing might become useful in targeting interventions towards older adults most likely to lose physical independence.

Sarcopenia, Obesity, and Sarcopenic Obesity: Relationship with Skeletal Muscle Phenotypes and Single Nucleotide Polymorphisms.

Obesity may aggravate the effects of sarcopenia on skeletal muscle structure and function in the elderly, but no study has attempted to identify the gene variants associated with sarcopenia in obese women. Therefore, the aims of the present study were to: (1) describe neuromuscular function in sarcopenic and non-sarcopenic women with or without obesity; (2) identify gene variants associated with sarcopenia in older obese women. In 307 Caucasian women (71 ± 6 years, 66.3 ± 11.3 kg), skeletal muscle mass was estimated using bioelectric impedance, and function was tested with a 30 s one-leg standing-balance test. Biceps brachii thickness and vastus lateralis cross-sectional area (VLACSA) were measured with B-mode ultrasonography. Handgrip strength, maximum voluntary contraction elbow flexion (MVCEF), and knee extension torque (MVCKE) were measured by dynamometry, and MVCKE/VLACSA was calculated. Genotyping was performed for 24 single-nucleotide polymorphisms (SNPs), selected based on their previous associations with muscle-related phenotypes. Based on sarcopenia and obesity thresholds, groups were classified as sarcopenic obese, non-sarcopenic obese, sarcopenic non-obese, or non-sarcopenic non-obese. A two-way analysis of covariance was used to assess the main effects of sarcopenia and obesity on muscle-related phenotypes and binary logistic regression was performed for each SNP to investigate associations with sarcopenia in obesity. There were no significant obesity * sarcopenic status interactions for any of the investigated muscle-related phenotypic parameters. Neither sarcopenia nor obesity had a significant effect on biceps brachii thickness, but sarcopenia was associated with lower VLACSA (p = 0.003). Obesity was associated with lower MVCEF (p = 0.032), MVCKE (p = 0.047), and MVCKE/VLACSA (p = 0.012) with no significant effect of sarcopenia. Adjusted for age and height, three SNPs (ACTN3 rs1815739, MTHFR rs1801131, and MTHFR rs1537516) were associated with sarcopenia in obese participants. Sarcopenia was associated with a smaller muscle size, while obesity resulted in a lower muscle quality irrespective of sarcopenia. Three gene variants (ACTN3 rs1815739, MTHFR rs1801131, and MTHFR rs1537516) suspected to affect muscle function, homocysteine metabolism, or DNA methylation, respectively, were associated with sarcopenia in obese elderly women. Understanding the skeletal muscle features affected by sarcopenia and obesity, and identification of genes related to sarcopenia in obese women, may facilitate early detection of individuals at particular risk of sarcopenic obesity.

Dietary Protein Requirement Threshold and Micronutrients Profile in Healthy Older Women Based on Relative Skeletal Muscle Mass.

Although multiple nutrients have shown protective effects with regard to preserving muscle function, the recommended amount of dietary protein and other nutrients profile on older adults for maintenance of high muscle mass is still debatable. The aims of this paper were to: (1) identify dietary differences between older women with low and high relative skeletal muscle mass, and (2) identify the minimal dietary protein intake associated with high relative skeletal muscle mass and test the threshold ability to determine an association with skeletal muscle phenotypes. Older women (n = 281; 70 ± 7 years, 65 ± 14 kg), with both low and high relative skeletal muscle mass groups, completed a food questionnaire. Skeletal muscle mass, fat-free mass (FFM), biceps brachii thickness, vastus lateralis anatomical cross-sectional area (VLACSA), handgrip strength (HGS), maximum elbow flexion torque (MVCEF), maximum knee extension torque (MVCKE), muscle quality (HGS/Body mass), and fat mass were measured. Older women with low relative skeletal muscle mass had a lower daily intake of protein, iodine, polyunsaturated fatty acid (PUFA), Vit E, manganese, milk, fish, nuts and seeds (p < 0.05) compared to women with high relative skeletal muscle mass. The minimum required dietary protein intake for high relative skeletal muscle mass was 1.17 g/kg body mass/day (g/kg/d) (sensitivity: 0.68; specificity: 0.62). Women consuming ≥1.17 g/kg/d had a lower BMI (B = -3.9, p < 0.001) and fat mass (B = -7.8, p < 0.001), and a higher muscle quality (B = 0.06, p < 0.001). The data indicate that to maintain muscle mass and function, older women should consume ≥1.17 g/kg/d dietary protein, through a varied diet including milk, fish and nuts that also contain polyunsaturated fatty acid (PUFA) and micronutrients such as iodine, Vit E and manganese.

Meta-analysis of genome-wide DNA methylation and integrative omics of age in human skeletal muscle.

BACKGROUND: Knowledge of age-related DNA methylation changes in skeletal muscle is limited, yet this tissue is severely affected by ageing in humans. METHODS: We conducted a large-scale epigenome-wide association study meta-analysis of age in human skeletal muscle from 10 studies (total n = 908 muscle methylomes from men and women aged 18-89 years old). We explored the genomic context of age-related DNA methylation changes in chromatin states, CpG islands, and transcription factor binding sites and performed gene set enrichment analysis. We then integrated the DNA methylation data with known transcriptomic and proteomic age-related changes in skeletal muscle. Finally, we updated our recently developed muscle epigenetic clock (https://bioconductor.org/packages/release/bioc/html/MEAT.html). RESULTS: We identified 6710 differentially methylated regions at a stringent false discovery rate <0.005, spanning 6367 unique genes, many of which related to skeletal muscle structure and development. We found a strong increase in DNA methylation at Polycomb target genes and bivalent chromatin domains and a concomitant decrease in DNA methylation at enhancers. Most differentially methylated genes were not altered at the mRNA or protein level, but they were nonetheless strongly enriched for genes showing age-related differential mRNA and protein expression. After adding a substantial number of samples from five datasets (+371), the updated version of the muscle clock (MEAT 2.0, total n = 1053 samples) performed similarly to the original version of the muscle clock (median of 4.4 vs. 4.6 years in age prediction error), suggesting that the original version of the muscle clock was very accurate. CONCLUSIONS: We provide here the most comprehensive picture of DNA methylation ageing in human skeletal muscle and reveal widespread alterations of genes involved in skeletal muscle structure, development, and differentiation. We have made our results available as an open-access, user-friendly, web-based tool called MetaMeth (https://sarah-voisin.shinyapps.io/MetaMeth/).

Leveling the Playing Field: A New Proposed Method to Address Relative Age- and Maturity-Related Bias in Soccer.

Despite various solutions proposed to solve the relative age effect (RAE), it is still a major problem confounding talent identification and selection processes. In the first phase, we sampled 302 under 7-21 academy soccer players from two Belgian professional soccer clubs to explore the potential of a new approach to solve the inequalities resulting from relative age- and maturity-related bias. This approach allocates players into four discrete quartile groups based on the midway point of their chronological and estimated developmental (ED) birth dates (calculated using the growth curves for stature of Belgian youth). With the use of chi square analyses, a RAE was found (p < 0.01) for the overall sample (Q1 = 41.4% vs. Q4 = 14.9%) that completely disappeared after reallocation (Q1 = 26.5%; Q2 = 21.9%; Q3 = 27.5%; Q4 = 24.2%). According to the new allocation method, the stature difference was reduced, on average, by 11.6 cm (from 24.0 ± 9.9 to 12.4 ± 3.4 cm, d = 1.57). Body mass difference between the two methods was 1.9 kg (20.1 ± 11.3-18.2 ± 13.1 kg, respectively, d = 0.15). The new method created a maximum chronological age difference of 1.9 vs. 0.8 years for the current method. With the use of this method, 47% of the players would be reallocated. Twenty-three percent would be moved up one age category, and 21% would be moved down. In the second phase, we also examined 80 UK academy soccer players to explore if reallocating players reduces the within-playing group variation of somatic and physical fitness characteristics. The percentage coefficient of variation (%CV) was reduced (0.2-10.1%) in 15 out of 20 metrics across U11-U16 age categories, with the U13 age category demonstrating the largest reductions (0.9-10.1%) in CV. The U12 and U13 age categories and associated reallocation groupings showed trivial to small (ES = 0.0-0.5) between-method differences and trivial to moderate (ES = 0.0-1.1) differences within the U14-U16 age categories. A reduction in RAE may lead to fewer dropouts and thus a larger player pool, which benefits, in turn, talent identification, selection, and development.

Static one-leg standing balance test as a screening tool for low muscle mass in healthy elderly women.

BACKGROUND: Identification of simple screening tools for detecting lower skeletal muscle mass may be beneficial for planning effective interventions in the elderly. AIMS: We aimed to (1) establish a threshold for one-leg standing balance test (OLST) time for low muscle mass, and (2) test the ability of that threshold to assess muscular impairments in a poor balance group. METHODS: Eyes-open OLST (maximum duration 30 s) was performed with right and left legs in 291 women (age 71 ± 6 years). OLST time was calculated as the sum of the OLST time of right and left legs. Fat-free mass (FFM), skeletal muscle mass (SMM), fat mass, biceps brachii and vastus lateralis sizes; handgrip strength (HGS), elbow flexion maximum torque (MVCEF) and knee extension maximum torque (MVCKE) were measured. Muscle quality was calculated as MVCKE/FFM and physical activity was assessed by questionnaire. Low muscle mass was defined as SMMrelative of 22.1%, a previously established threshold for pre-sarcopenia. RESULTS: The OLST threshold time to detect low muscle mass was 55 s (sensitivity: 0.63; specificity: 0.60). The poor balance group (OLST < 55 s) had higher fat mass (3.0%, p < 0.001), larger VL thickness (5.1%, p = 0.016), and lower HGS (- 10.2%, p < 0.001), MVCEF (- 8.2%, p = 0.003), MVCKE (- 9.5%, p = 0.012), MVCKE/FFM (- 11.0%, p = 0.004) and physical activity (- 8.0%, p = 0.024) compared to the normal balance group. While after adjusting age, the differences exist for HGS, fat mass and VL thickness only. DISCUSSION: An OLST threshold of 55 s calculated as the summed score from both legs discriminated pre-sarcopenic characteristics among active, community-dwelling older women with limited potential (sensitivity 0.63, specificity 0.60). CONCLUSION: OLST, which can be performed easily in community settings without the need for more complex muscle mass measurement, may help identify women at risk of developing sarcopenia.

Genetics of somatotype and physical fitness in children and adolescents.

OBJECTIVES: To analyze the influence of genetic and environmental factors on the variation in somatotype, physical fitness, and their mutual associations. METHODS: Twins from 214 pairs (87 monozygotic) of the Autonomous Region of Madeira, Portugal, from 3 to 18 years of age (51% girls) were assessed in anthropometry and physical fitness tests. We estimated endomorphy, mesomorphy, and ectomorphy based on anthropometric measures and physical fitness using the Eurofit test battery. Two age categories were analyzed: children (3-11 years) and adolescents (12-18 years). Genetic and environmental variations were estimated using quantitative genetic twin modeling. RESULTS: No genetic sex differences were found, thus boys and girls were pooled in all genetic analyses. Heritability estimates were high for somatotype (a2  = 0.80-0.93), physical fitness traits (a2  = 0.67-0.83), and largely similar in children and adolescents. Positive correlations were found for ectomorphy with motor ability and cardiorespiratory endurance as well as for endomorphy and mesomorphy with muscular strength (r = 0.25-0.37). In contrast, negative associations were found for ectomorphy with muscular strength, as well as for endomorphy and mesomorphy with motor ability and cardiorespiratory endurance (-0.46 to -0.26). Twin modeling indicated that these associations were explained mostly by genetic factors in common to the two associated traits (84% or more). CONCLUSIONS: Associations between somatotype and physical fitness tests are mainly explained by common genetic background in children and adolescents. Therefore, interventions in youth should consider that a child's performance in physical fitness tests partly reflects their inherited physique.

The Association of Multiple Gene Variants with Ageing Skeletal Muscle Phenotypes in Elderly Women.

There is a scarcity of studies that have investigated the role of multiple single nucleotide polymorphisms (SNPs) on a range of muscle phenotypes in an elderly population. The present study investigated the possible association of 24 SNPs with skeletal muscle phenotypes in 307 elderly Caucasian women (aged 60-91 years, 66.3 ± 11.3 kg). Skeletal muscle phenotypes included biceps brachii thickness, vastus lateralis cross-sectional areas, maximal hand grip strength, isometric knee extension and elbow flexion torque. Genotyping for 24 SNPs, chosen on their skeletal muscle structural or functional links, was conducted on DNA extracted from blood or saliva. Of the 24 SNPs, 10 were associated with at least one skeletal muscle phenotype. HIF1A rs11549465 was associated with three skeletal muscle phenotypes and PTK2 rs7460 and ACVR1B rs10783485 were each associated with two phenotypes. PTK2 rs7843014, COL1A1 rs1800012, CNTF rs1800169, NOS3 rs1799983, MSTN rs1805086, TRHR rs7832552 and FTO rs9939609 were each associated with one. Elderly women possessing favourable genotypes were 3.6-13.2% stronger and had 4.6-14.7% larger muscle than those with less favourable genotypes. These associations, together with future work involving a broader range of SNPs, may help identify individuals at particular risk of an age-associated loss of independence.

Associations of combined genetic and epigenetic scores with muscle size and muscle strength: a pilot study in older women.

BACKGROUND: Inter-individual variance in skeletal muscle is closely related to genetic architecture and epigenetic regulation. Studies have examined genetic and epigenetic relationships with characteristics of ageing muscle separately, while no study has combined both genetic and epigenetic profiles in ageing muscle research. The aim of this study was to evaluate the association between combined genetic and methylation scores and skeletal muscle phenotypes in older women. METHODS: Forty-eight older Caucasian women (aged 65-79 years) were included in this study. Biceps brachii thickness and vastus lateralis anatomical cross-sectional area (ACSAVL ) were measured by ultrasonography. Maximum isometric elbow flexion (MVCEF ) and knee extension (MVCKE ) torques were measured by a customized dynamometer. The muscle-driven genetic predisposition score (GPSSNP ) was calculated based on seven muscle-related single nucleotide polymorphisms (SNPs). DNA methylation levels of whole blood samples were analysed using Infinium MethylationEPIC BeadChip arrays. The DNA methylation score was calculated as a weighted sum of methylation levels of sarcopenia-driven CpG sites (MSSAR ) or an overall gene-wise methylation score (MSSNP , the mean methylation level of CpG sites located in muscle-related genes). Linear regression models were built to study genetic and epigenetic associations with muscle size and strength. Three models were built with both genetic and methylation scores: (1) MSSAR  + GPSSNP , (2) MSSNP  + GPSSNP , and (3) gene-wise combined scores which were calculated as the ratio of the SNP score to the mean methylation level of promoters in the corresponding gene. Additional models with only a genetic or methylation score were also built. All models were adjusted for age and BMI. RESULTS: MSSAR was negatively associated with ACSAVL , MVCEF , and MVCKE and explained 10.1%, 35.5%, and 40.1% of the variance, respectively. MSSAR explained more variance in these muscular phenotypes than GPSSNP , MSSNP , and models including both genetic and methylation scores. MSSNP and GPSSNP accounted for less than 8% and 5% of the variance in all muscular phenotypes, respectively. The genotype and methylation level of CNTF was positively related to MVCKE (P = 0.03) and explained 12.2% of the variance. The adjusted R2 and Akaike information criterion showed that models with only a MSSAR performed the best in explaining inter-individual variance in muscular phenotypes. CONCLUSIONS: Our results improve the understanding of inter-individual variance in muscular characteristics of older women and suggest a possible application of a sarcopenia-driven methylation score to muscle strength estimation in older women while the combination with a genetic score still needs to be further studied.

The Genetic Effect on Muscular Changes in an Older Population: A Follow-Up Study after One-Year Cessation of Structured Training.

Older adults lose muscle mass and strength at different speeds after the cessation of physical exercise, which might be genotype related. This study aimed to explore the genetic association with changes in muscle mass and strength one year after the cessation of structured training in an older population. Participants (n = 113, aged between 61 and 81 years) who performed one-year of combined fitness (n = 44) or whole-body vibration (n = 69) training were assessed one year after the cessation of the training. Whole-body skeletal muscle mass and knee strength were measured. Data-driven genetic predisposition scores (GPSs) were calculated and analysed in a general linear model with sex, age, body mass index and post-training values of skeletal muscle mass or muscle strength as covariates. Forty-six single nucleotide polymorphisms (SNPs) from an initial 170 muscle-related SNPs were identified as being significantly linked to muscular changes after cessation. Data-driven GPSs and over time muscular changes were significantly related (p < 0.01). Participants with higher GPSs had less muscular declines during the cessation period while data-driven GPSs accounted for 26-37% of the phenotypic variances. Our findings indicate that the loss of training benefits in older adults is partially genotype related.

Prevalence and association of single nucleotide polymorphisms with sarcopenia in older women depends on definition.

The prevalence of sarcopenia depends on the definition used. There are, however, consistent sarcopenic characteristics, including a low muscle mass and muscle strength. Few studies have investigated the relationship between sarcopenia and genotype. A cross-sectional study was conducted with 307 community-dwelling ≥60-year-old women in South Cheshire, UK. Handgrip strength was assessed with a handgrip dynamometer and skeletal muscle mass was estimated using bioelectrical impedance. DNA was extracted from saliva (∼38%) or blood (∼62%) and 24 single-nucleotide polymorphisms (SNPs) were genotyped. Three established sarcopenia definitions - %Skeletal Muscle Mass (%SMM), Skeletal Muscle Mass Index (SMI) and European Working Group on Sarcopenia in Older People (EWGSOP) - were used to assess sarcopenia prevalence. Binary logistic regression with age as covariate was used to identify SNPs associated with sarcopenia. The prevalence of sarcopenia was: %SMM 14.7%, SMI 60.6% and EWGSOP 1.3%. Four SNPs were associated with the %SMM and SMI definitions of sarcopenia; FTO rs9939609, ESR1 rs4870044, NOS3 rs1799983 and TRHR rs7832552. The first three were associated with the %SMM definition, and TRHR rs7832552 with the SMI definition, but none were common to both sarcopenia definitions. The gene variants associated with sarcopenia may help proper counselling and interventions to prevent individuals from developing sarcopenia.

The effect of resistance training, detraining and retraining on muscle strength and power, myofibre size, satellite cells and myonuclei in older men.

INTRODUCTION: Ageing is associated with an attenuated hypertrophic response to resistance training and periods of training interruptions. Hence, elderly would benefit from the 'muscle memory' effects of resistance training on muscle strength and mass during detraining and retraining. As the underlying mechanisms are not yet clear, this study investigated the role of myonuclei during training, detraining and retraining by using PCM1 labelling in muscle cross-sections of six older men. METHODS: Knee extension strength and power were measured in 30 older men and 10 controls before and after 12 weeks resistance training and after detraining and retraining of similar length. In a subset, muscle biopsies from the vastus lateralis were taken for analysis of fibre size, fibre type distribution, Pax7+ satellite cell number and myonuclear domain size. RESULTS: Resistance training increased knee extension strength and power parameters (+10 to +36%, p < .001) and decreased the frequency of type IIax fibres by half (from 20 to 10%, p = .034). Detraining resulted in a modest loss of strength and power (-5 to -15%, p ≤ .004) and a trend towards a fibre-type specific decrease in type II fibre cross-sectional area (-17%, p = .087), type II satellite cell number (-30%, p = .054) and type II myonuclear number (-12%, p = .084). Less than eight weeks of retraining were needed to reach the post-training level of one-repetition maximum strength. Twelve weeks of retraining were associated with type II fibre hypertrophy (+29%, p = .050), which also promoted an increase in the number of satellite cells (+72%, p = .036) and myonuclei (+13%, p = .048) in type II fibres. Changes in the type II fibre cross-sectional area were positively correlated with changes in the myonuclear number (Pearson's r between 0.40 and 0.73), resulting in a stable myonuclear domain. CONCLUSION: Gained strength and power and fibre type changes were partially preserved following 12 weeks of detraining, allowing for a fast recovery of the 1RM performance following retraining. Myonuclear number tended to follow individual changes in type II fibre size, which is in support of the myonuclear domain theory.

Differentially methylated gene patterns between age-matched sarcopenic and non-sarcopenic women.

BACKGROUND: Sarcopenia is characterized by progressive decreases in muscle mass, muscle strength, and muscle function with ageing. Although many studies have investigated the mechanisms of sarcopenia, its connection with epigenetic factors, such as DNA methylation, still remains poorly understood. The aim of this study was to explore sarcopenia-related DNA methylation differences in blood samples between age-matched sarcopenic and non-sarcopenic older women. METHODS: A sarcopenic group (n = 24) was identified and selected from a set of 247 older Caucasian women (aged 65-80 years) based on cut-off points of skeletal muscle index at 6.75 kg/m2 and grip strength at 26 kg (the lower quintile of grip strength in the set). A non-sarcopenic group (n = 24) was created with a similar age distribution as that of the sarcopenic group. DNA methylation patterns of whole blood samples from both groups were analysed using Infinium MethylationEPIC BeadChip arrays. Differentially methylated cytosin-phosphate-guanine sites (dmCpGs) were identified at a P value threshold of 0.01 by comparing methylation levels between the sarcopenic and non-sarcopenic groups at each CpG site. dmCpG-related genes were annotated based on Homo sapiens hg19 genome build. The functions of these genes were further examined by GO and KEGG pathway enrichment analysis. RESULTS: The global methylation level of all analysed CpG sites (n = 788 074) showed no significant difference between the sarcopenic and non-sarcopenic groups (0.812), while the average methylation level of dmCpGs (n = 6258) was significantly lower in the sarcopenic group (0.004). The sarcopenic group had significantly higher methylation levels in TSS200 (the region from transcription start site to 200 nucleotides upstream of the site) and lower methylation levels in gene body and 3'UTR regions. In respect of CpG regions, CpG islands in promoters and some intragenic regions showed greater levels of methylation in the sarcopenic group. dmCpG-related KEGG pathways were mainly associated with muscle function, actin cytoskeleton regulation, and energy metabolism. Seven genes (HSPB1, PBX4, CNKSR3, ORMDL3, MIR10A, ZNF619, and CRADD) were found with the same methylation direction as previous studies of blood sample methylation during ageing. Fifty-four genes were shared with previous studies of resistance training. CONCLUSIONS: Our results improve understanding of epigenetic mechanisms of sarcopenia by identifying sarcopenia-related DNA methylation differences in blood samples of older women. These methylation differences suggest underlying alterations of gene expression and pathway function, which can partially explain sarcopenia-related muscular changes.

The stiffness response of type IIa fibres after eccentric exercise-induced muscle damage is dependent on ACTN3 r577X polymorphism.

The aim of the study was to determine the effect of α-actinin-3 (ACTN3) deficiency (XX) on muscle damage induced by an eccentric exercise bout. In this purpose, 4 RR and 4 XX individuals performed an intensive eccentric knee flexion exercise on an isokinetic dynamometer. Muscle biopsies, blood and pain scores were taken before and after the exercise to determine the extent of the exercise-induced damage and the effect of the ACTN3 R577X polymorphism. Maximal isometric strength of the quadriceps and single fibre properties were compared before and after the exercise. The drop in maximal isometric strength of the quadriceps at 45° knee flexion following the eccentric exercise bout was on average 37% 24 h post-exercise. The decrease in force was also apparent in isolated type IIa fibres (8%; P = 0.02), but not in type I fibres (P = 0.88). Creatine kinase and myoglobin plasma levels increased in all participants at least by 55% and 87%, respectively (P < 0.05). In addition, mRNA levels of markers for muscle regeneration and muscle remodelling increased after the eccentric exercise (P < 0.05), however, independently from ACTN3 R577X genotype. The mRNA level of nuclear factor of activated T-cells 1 (NFATc1) decreased after the eccentric exercise only in XX genotypes (P < 0.05). The stiffness of type IIa, but not type I muscle fibres increased only in RR individuals after the eccentric exercise (P < 0.05). While no major effect of α-actinin-3 deficiency on susceptibility to muscle damage was found acutely, the increased stiffness response in fast RR fibres might be a protection mechanism from muscle damage during a subsequent eccentric exercise bout.