2026/02/12 by Charles Hwang, Siti Rahmayanti, Yori Endo +5 · 1 voice
Biochemistry, Genetics and Molecular Biology · #Genetics and Physical Performance #Genetics, Aging, and Longevity in Model Organisms #Muscle Physiology and Disorders
paper · doi:10.18632/aging.206382
openalex publication_date 2026/02/12 · openalex created_date 2026/05/19 · openalex updated_date 2026/07/22
Animal models provide a crucial scientific substrate for medical innovation, yet findings in these models do not always translate directly to humans. Although murine models are extensively employed to study skeletal muscle aging, the extent to which they diverge from the human aging process remains poorly understood. This study examined transcriptional changes with aging in mouse and human skeletal muscle. RNA bulk-sequencing was performed on gastrocnemius muscles from young and old C57BL/6 mice and compared to transcriptomic data from young and old healthy human vastus lateralis muscles obtained from the GESTALT study (NIA/NIH) via the Gene Expression Omnibus database. Cross-species comparison revealed substantial divergence in age-associated transcriptional profiles, with fewer than 5% of significant GO and KEGG terms shared between species. Hypoxia signaling, VEGFA, and inflammatory pathways showed concordant downregulation with aging in both species; however, angiogenesis, neurogenesis, and myogenesis demonstrated opposing or non-significant trends. These findings caution against direct extrapolation of murine aging transcriptomics to human skeletal muscle biology, though select conserved pathways may represent viable cross-species targets for future investigation.