Molecular signatures underlying heterogeneous hypertrophy responsiveness to resistance training in older men and women: a within-subject design
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PROVIDER: PRJNA1164267 | ENA |
REPOSITORIES: ENA
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Project description:We showed higher resistance training (RT) volume (4-sets) offsets muscle hypertrophy non-responsiveness to single-set RT (1-set), while enhancing hypertrophic response among responders. Here, we investigated molecular traits underpinning RT-related hypertrophic variability via targeted (ribosome density and biogenesis) and untargeted approaches (RNAseq gene-ontology (GO) and Pathway-Level Information ExtractoR [PLIER]). Twenty-seven older (693 years) participants in the parental trial had one leg randomly allocated to 1-set and the contralateral leg allocated to 4-sets of RT for 10-wk, 2x/week. Pre- and postintervention, participants underwent magnetic resonance imaging (MRI) and muscle biopsies. We selected participants based on quadriceps muscle cross-sectional area (qCSA) changes and used the MRI typical error (2xTE=3.27%) to allocate those in distinct hypertrophy phenotype: low-responders: blunted hypertrophy, regardless of RT-volume; medium-responders: hypertrophy only following the higher RT-volume; and high-responders: hypertrophy following both RT-volume. The qCSA was higher for 4-sets compared with 1-set for medium- and high-responders only. Higher RT-volume, regardless of responsiveness groups, was followed by increased Frizzled-1 protein expression. RNAseq showed that high-responder’s robust hypertrophy was followed by up-regulation of pathways linked with protein turnover metabolism, RT-related metabolic response, and with protein-folding biological processes. Hypertrophy in medium-responders was marked by down-regulation of pathways linked with muscle catabolism (Proteasome and Spliceosome), modulations on distinct RT-related metabolic response, and biological processes associated with hormone- and steroid-related pathways. Low-responders, on the other hand, did not show measurable changes in any molecular pathways, regardless of RT volume manipulation. Overall, these finding reveal differential molecular signatures across the spectrum of RT responsiveness among older individuals.
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Project description:Evidence from clinical trials and observational studies suggests that both progressive resistance training (PRT) and metformin delay a variety of age-related morbidities. Previously, we completed a clinical trial testing the effects of 14 weeks of PRT + metformin (metPRT) compared to PRT with placebo (plaPRT) on muscle hypertrophy in older adults. We found that metformin blunted PRT-induced muscle hypertrophic response. To understand potential mechanisms underlying the inhibitory effect of metformin on PRT, we analyzed the muscle transcriptome in 23 metPRT and 24 plaPRT participants. PRT significantly increased expression of genes involved in extracellular matrix remodeling pathways, and downregulated RNA processing pathways in both groups, however, metformin blunted the number of differentially expressed genes within these pathways compared to plaPRT. Pathway analysis showed that genes unique to metPRT modulated aging-relevant pathways, such as cellular senescence and autophagy. Differentially expressed genes from baseline biopsies in older adults compared to resting muscle from young volunteers were reduced following PRT in plaPRT and were further reduced in metPRT. We suggest that although metformin may blunt pathways induced by PRT to promote muscle hypertrophy, adjunctive metformin during PRT may have beneficial effects on aging-associated pathways in muscle from older adults.
2020-09-08 | GSE157585 | GEO
Project description:Shatavari is a herbal dietary supplement that may increase skeletal muscle strength in younger and older adults. Shatavari contains compounds with both estradiol-like and antioxidant properties, which could enhance muscle function. Postmenopausal women may derive the greatest benefit, as estrogen deficiency adversely impacts skeletal muscle function. However, mechanistic insights are limited and the effects of shatavari on muscle function require further characterization. In this randomised, double-blind trial, 17 young (23 ±5yr) and 22 older (63±5yr) women completed an eight-week leg resistance training programme. They consumed either a placebo or shatavari (1000mg/d, equivalent to 26,500 mg/d fresh weight) supplement throughout. Pre and post training, measures of leg strength, neuromuscular function and vastus lateralis (VL) biopsies were obtained. Tandem-mass-tagged VL proteomic analyses were performed. Additionally, resistance training (RT) is the gold standard intervention for ameliorating sarcopenia. Outstanding mechanistic questions remain regarding the malleability of the molecular determinants of skeletal muscle function in older age. Discovery proteomics can expand such knowledge. We further aimed to compare the effect of RT on the skeletal muscle proteome and neuromuscular function (NMF) in older and younger women.
2024-10-22 | PXD056507 | Pride
Project description:Several studies comparing resistance training (RT) frequencies may have been affected by the large between-subject variability. This study aimed to compare the changes in lower limbs maximal dynamic strength (1RM) and quadriceps femoris cross-sectional area (CSA) after a RT with different weekly frequencies in strength-trained individuals using a within-subject design. Twenty-four men participated in a 9-week RT program, being randomly divided into two conditions: resistance training with equalized total training volume (RTEV) and with unequalized total training volume (RTUV). The RT protocol used the unilateral leg press 45° exercise and each subject's lower limb executed one of the proposed frequencies (one and three times/week). All conditions effectively increased 1RM and CSA (p<0.001); however, no significant differences were observed in the values of 1RM (p = 0.454) and CSA (p = 0.310) between the RT frequencies in the RTEV and RTUV conditions. Therefore, RT performed three times a week showed similar increases in 1RM and CSA to the program performed once a week, regardless of training volume equalization. Nevertheless, when the higher RT frequency allowed the application of a greater TTV (i.e., RTUV), higher effect size (ES) values (0.51 and 0.63, 1RM and CSA, respectively) were observed for the adaptations.
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2020-06-19 | MSV000085611 | MassIVE
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2024-04-08 | MSV000094489 | MassIVE
Project description:Older individuals were subjected to complete bed rest for 10 days. Muscle biopsies from the vastus lateralis were obtained immediately prior and at the conclusion of the bed rest. RNA-sequencing was performed to determine the gene expression changes associated with bed rest. Marked decrease in the expression of genes associated with mitochondrial energy metabolism including fatty acid oxidation, TCA cycle and the electron transport chain was observed. Upstream regulator analysis revealed that many of these genes are downstream targets of the transcription factors PPAR, ERR and PGC-1alpha.
2019-09-24 | GSE126865 | GEO
Project description:BackgroundAdequate muscle fibre perfusion is critical for the maintenance of muscle mass; it is essential in the rapid delivery of oxygen, nutrients and growth factors to the muscle, stimulating muscle fibre growth. Muscle fibre capillarization is known to decrease substantially with advancing age. However, whether (relative) low muscle fibre capillarization negatively impacts the muscle hypertrophic response following resistance exercise training in older adults is unknown.MethodsTwenty-two healthy older men (71 ± 1 years) performed 24 weeks of progressive resistance type exercise training. To assess the change in muscle fibre characteristics, percutaneous biopsies from the vastus lateralis muscle were taken before and following 12 and 24 weeks of the intervention programme. A comparison was made between participants who had a relatively low type II muscle fibre capillary-to-fibre perimeter exchange index (CFPE; LOW group) and high type II muscle fibre CFPE (HIGH group) at baseline. Type I and type II muscle fibre size, satellite cell, capillary content and distance between satellite cells to the nearest capillary were determined by immunohistochemistry.ResultsOverall, type II muscle fibre size (from 5150 ± 234 to 6719 ± 446 µm2 , P < 0.05) and satellite cell content (from 0.058 ± 0.006 to 0.090 ± 0.010 satellite cells per muscle fibre, P < 0.05) had increased significantly in response to 24 weeks of resistance exercise training. However, these improvements where mainly driven by differences in baseline type II muscle fibre capillarization, whereas muscle fibre size (from 5170 ± 390 to 7133 ± 314 µm2 , P < 0.05) and satellite cell content (from 0.059 ± 0.009 to 0.102 ± 0.017 satellite cells per muscle fibre, P < 0.05) increased significantly in the HIGH group, no significant changes were observed in LOW group following exercise training. No significant changes in type I and type II muscle fibre capillarization were observed in response to 12 and 24 weeks of resistance exercise training in both the LOW and HIGH group.ConclusionsType II muscle fibre capillarization at baseline may be a critical factor for allowing muscle fibre hypertrophy to occur during prolonged resistance exercise training in older men.
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