Pescatello, L. S. | bioRxiv Science

bioRxiv2025

Muscle Strength and Size Relationships with Unilateral Progressive Resistance Training

PurposeThis study defines correlative and causal relationships between muscle strength and size before and after unilateral resistance training (RT) in a large cohort of healthy adults, focusing on sex differences within these relationships. MethodsResults from 1233 participants (504 males and 729 females) in a retrospective analysis were included. Maximal voluntary isometric contraction strength (MVC), one-repetition maximum strength (1RM), biceps cross-sectional area (CSA) and elbow flexor volume (VOL) measures of the non-dominant and dominant arm were evaluated from baseline and after 12-wk RT twice per week. Correlations of MVC and VOL and 1RM and VOL were calculated in the whole cohort and within each sex independently. Causal analysis modeling was used to infer mechanistic relationships among variables. ResultsAbsolute muscle strength and size related to one another both at baseline and following training, however correlation strength in each sex were weak. After RT, MVC relative change and VOL relative change correlations were correlated for the whole cohort (r=0.16; p<0.001) and females (r=0.18; p<0.001), but not in males (r=0.11; p=0.07). No significant correlations for relative change in 1RM and VOL were observed for the whole cohort or within sex. Causal discovery determined that change in VOL caused significant change in 1RM (but not MVC) and age was identified as a potential cause. ConclusionsSex differences occur in muscle size and strength relationship adaptations following resistance training, most notably the absence of significant relationships between relative size and strength changes in men. Simpsons paradox bias, where assessing the combined data of males and females (also affecting overall sample size) affects identifies patterns differently than assessing relationships within each sex, may partially explain our findings.

physiology↗

bioRxiv2023

It All Rolls Downstream: Upstream Control of Physical Activity Regulation

Physical activity is regulated by a variety of genetic molecules. However, the pathways through which those molecules work to regulate activity is largely unknown. The purpose of this study was to gather the known genetic molecules that are associated with activity regulation and define overall upstream regulator pathways through which these molecules work. We conducted a systematic review to gather all available published datasets related to physical activity regulation, standardized the data for genomic location and species, and used this data, in an unbiased manner to create a dataset that was used: (1) to physically map and visualize all identified molecules to homologous chromosome locations and (2) as the dataset for which an Upstream Regulator Analysis (URA) was conducted using Qiagen Ingenuity Pathway Analysis (IPA) software. Our search resulted in 469 genetic molecules (e.g. genomic variant, transcript, protein, micro-RNA) that were split into brain (n=366) and muscle (n=345) sub-groups, which was our attempt to separate differences in central vs peripheral pathways. The brain and muscle data sets had several potential upstream regulators, the top-rated being {beta}-estradiol as a regulator for 19.5% and 21% of the brain and muscle datasets respectively. To our knowledge, {beta}-estradiols identification as a potential regulator, is the first evidence to link the well-known effects of sex hormones on physical activity with genetic regulation of physical activity. There were a variety of potential upstream regulators for the molecules collected in this review, but interestingly, three of the top five for both brain and muscle are nuclear receptor binding ligands; estradiol (estrogen receptor), dexamethasone (glucocorticoid receptor), and tretinoin (retinoic acid receptor), indicating a potential role of nuclear receptors in the regulation of physical activity. Selective nuclear receptor modulation may be an area of interest in future mechanistic studies of the genetic regulation of physical activity.

genetics↗