ArticleBiology of sex differences2023
Evidence for sex-specific intramuscular changes associated to physical weakness in adults older than 75 years.
Article in Biology of sex differences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- Sex differences in human skeletal muscle fiber types and the influence of age, physical activity, and muscle group: A systematic review and meta-analysis.Physiological reports · 2025Pooled it
- SK channel upregulation and sex-specific mechanisms drive spinal motoneuron reduced excitability with age.Frontiers in aging neuroscience · 2026Article
- Biomarkers of Metabolism and Inflammation in Individuals with Obesity and Normal Weight: A Comparative Analysis Exploring Sex Differences.International journal of molecular sciences · 2025Article
- SkeletAge: Transcriptomics-based Aging Clock Identifies 26 New Targets in Skeletal Muscle Aging.bioRxiv : the preprint server for biology · 2025Article
- Sex differences of fall-risk-increasing drugs in the middle-aged and elderly: a descriptive, cross-sectional study of FDA adverse event reporting system.Scientific reports · 2024Article
- Development and Validation of a Risk Prediction Model for Frailty in Patients with Chronic Diseases.Gerontology & geriatric medicineArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPhysical weakness is a key component of frailty, and is highly prevalent in older adults. While females have a higher prevalence and earlier onset, sex differences in the development of frailty-related physical weakness are hardly studied. Therefore, we investigated the intramuscular changes that differentiate between fit and weak older adults for each sex separately.
methodsMale (n = 28) and female (n = 26) older adults (75 + years) were grouped on the basis of their ranks according to three frailty-related physical performance criteria. Muscle biopsies taken from vastus lateralis muscle were used for transcriptome and histological examination. Pairwise comparisons were made between the fittest and weakest groups for each sex separately, and potential sex-specific effects were assessed.
resultsWeak females were characterized by a higher expression of inflammatory pathways and infiltration of NOX2-expressing immune cells, concomitant with a higher VCAM1 expression. Weak males were characterized by a smaller diameter of type 2 (fast) myofibers and lower expression of PRKN. In addition, weakness-associated transcriptome changes in the muscle were distinct from aging, suggesting that the pathophysiology of frailty-associated physical weakness does not necessarily depend on aging.
conclusionsWe conclude that physical weakness-associated changes in muscle are sex-specific and recommend that sex differences are taken into account in research on frailty, as these differences may have a large impact on the development of (pharmaceutical) interventions against frailty. TRIAL REGISTRATION NUMBER: The FITAAL study was registered in the Dutch Trial Register, with registration code NTR6124 on 14-11-2016 ( https://trialsearch.who.int/Trial2.aspx?TrialID=NTR6124 ). HIGHLIGHTS: • In female, but not male older adults, physical weakness was associated with a higher expression of intramuscular markers for inflammation. • In male, but not female older adults, physical weakness was associated with a smaller diameter of type 2 (fast) myofibers and lower PRKN expression. • Fit older adults (of both sexes) maintained expression levels comparable to young participants of weakness related genes, differing from frail participants.
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