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Supporting Evidence for Inactivity and Chronic Inflammation to be Important in Muscle Aging
It is well known that muscle function can be sustained into late life to a greater degree than most people manage. Much of what is presently considered by most people to be normal loss of strength and muscle mass with aging is the result of a combination of a lack of exercise combined with lifestyle choices, such as becoming overweight, that generate chronic inflammation. Researchers here illustrate the point in a study of gene expression changes that take place in muscle tissue with age and other factors. The researchers compared age versus exercise and inflammatory status. At least by looking at the number of changes, chronological age has less of an effect on gene expression in muscle tissue than is the case for exercise and inflammation.
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.
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