Age-related changes in human skeletal muscle transcriptome and proteome are more affected by chronic inflammation and physical inactivity than primary aging.

Autor: Kurochkina NS; Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Russia., Orlova MA; Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Russia., Vigovskiy MA; Medical Research and Educational Center of Lomonosov Moscow State University, Moscow, Russia., Zgoda VG; Institute of Biomedical Chemistry, Moscow, Russia., Vepkhvadze TF; Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Russia., Vavilov NE; Institute of Biomedical Chemistry, Moscow, Russia., Makhnovskii PA; Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Russia., Grigorieva OA; Medical Research and Educational Center of Lomonosov Moscow State University, Moscow, Russia., Boroday YR; Medical Research and Educational Center of Lomonosov Moscow State University, Moscow, Russia., Philippov VV; Medical Research and Educational Center of Lomonosov Moscow State University, Moscow, Russia., Lednev EM; Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Russia., Efimenko AY; Medical Research and Educational Center of Lomonosov Moscow State University, Moscow, Russia., Popov DV; Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Russia.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2024 Apr; Vol. 23 (4), pp. e14098. Date of Electronic Publication: 2024 Feb 21.
DOI: 10.1111/acel.14098
Abstrakt: Evaluation of the influence of primary and secondary aging on the manifestation of molecular and cellular hallmarks of aging is a challenging and currently unresolved issue. Our study represents the first demonstration of the distinct role of primary aging and chronic inflammation/physical inactivity - the most important drivers of secondary aging, in the regulation of transcriptomic and proteomic profiles in human skeletal muscle. To achieve this purpose, young healthy people (n = 15), young (n = 8) and older (n = 37) patients with knee/hip osteoarthritis, a model to study the effect of long-term inactivity and chronic inflammation on the vastus lateralis muscle, were included in the study. It was revealed that widespread and substantial age-related changes in gene expression in older patients relative to young healthy people (~4000 genes regulating mitochondrial function, proteostasis, cell membrane, secretory and immune response) were related to the long-term physical inactivity and chronic inflammation rather than primary aging. Primary aging contributed mainly to the regulation of genes (~200) encoding nuclear proteins (regulators of DNA repair, RNA processing, and transcription), mitochondrial proteins (genes encoding respiratory enzymes, mitochondrial complex assembly factors, regulators of cristae formation and mitochondrial reactive oxygen species production), as well as regulators of proteostasis. It was found that proteins associated with aging were regulated mainly at the post-transcriptional level. The set of putative primary aging genes and their potential transcriptional regulators can be used as a resource for further targeted studies investigating the role of individual genes and related transcription factors in the emergence of a senescent cell phenotype.
(© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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