TY - JOUR
T1 - Sex-specific alteration in human muscle transcriptome with age
AU - Gharpure, Mohini
AU - Chen, Jie
AU - Nerella, Resheek
AU - Vyavahare, Sagar
AU - Kumar, Sandeep
AU - Isales, Carlos M.
AU - Hamrick, Mark
AU - Adusumilli, Satish
AU - Fulzele, Sadanand
N1 - Publisher Copyright:
© 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
PY - 2023/6
Y1 - 2023/6
N2 - Sarcopenia is a medical condition that progressively develops with age and results in reduced skeletal muscle mass, alteration in muscle composition, and decreased muscle strength. Several clinical studies suggested that sarcopenia disproportionally affects males and females with age. Despite this knowledge, the molecular mechanism governing the pathophysiology is not well understood in a sex-specific manner. In this study, we utilized human gastrocnemius muscles from males and females to identify differentially regulated genes with age. We found 269 genes with at least a twofold expression difference in the aged muscle transcriptome. Among the female muscle samples, there were 239 differentially regulated genes, and the novel protein-coding genes include KIF20A, PIMREG, MTRNR2L6, TRPV6, EFNA2, RNF24, and SFN. In aged male skeletal muscle, there were 166 differentially regulated genes, and the novel-protein coding genes are CENPK, CDKN2A, BHLHA15, and EPHA. Gene Ontology (GO) enrichment revealed glucose catabolism, NAD metabolic processes, and muscle fiber transition pathways that are involved in aged female skeletal muscle, whereas replicative senescence, cytochrome C release, and muscle composition pathways are disrupted in aged male skeletal muscle. Targeting these novels, differentially regulated genes, and signaling pathways could serve as sex-specific therapeutic targets to combat the age-related onset of sarcopenia and promote healthy aging.
AB - Sarcopenia is a medical condition that progressively develops with age and results in reduced skeletal muscle mass, alteration in muscle composition, and decreased muscle strength. Several clinical studies suggested that sarcopenia disproportionally affects males and females with age. Despite this knowledge, the molecular mechanism governing the pathophysiology is not well understood in a sex-specific manner. In this study, we utilized human gastrocnemius muscles from males and females to identify differentially regulated genes with age. We found 269 genes with at least a twofold expression difference in the aged muscle transcriptome. Among the female muscle samples, there were 239 differentially regulated genes, and the novel protein-coding genes include KIF20A, PIMREG, MTRNR2L6, TRPV6, EFNA2, RNF24, and SFN. In aged male skeletal muscle, there were 166 differentially regulated genes, and the novel-protein coding genes are CENPK, CDKN2A, BHLHA15, and EPHA. Gene Ontology (GO) enrichment revealed glucose catabolism, NAD metabolic processes, and muscle fiber transition pathways that are involved in aged female skeletal muscle, whereas replicative senescence, cytochrome C release, and muscle composition pathways are disrupted in aged male skeletal muscle. Targeting these novels, differentially regulated genes, and signaling pathways could serve as sex-specific therapeutic targets to combat the age-related onset of sarcopenia and promote healthy aging.
KW - Aging
KW - Muscle
KW - Sarcopenia
KW - Sex
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U2 - 10.1007/s11357-023-00795-5
DO - 10.1007/s11357-023-00795-5
M3 - Article
C2 - 37106281
AN - SCOPUS:85153725178
SN - 2509-2715
VL - 45
SP - 1303
EP - 1316
JO - GeroScience
JF - GeroScience
IS - 3
ER -