Cell-Specific Markers of Skeletal Muscle Aging, Frailty and Senescence

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Aging (Aging-US)

Aging-US published this cover paper in Volume 14, Issue 23, entitled, "Single nuclei profiling identifies cell specific markers of skeletal muscle aging, frailty, and senescence" by researchers from Buck Institute for Research on Aging, Novato, CA; Drug Discovery Research, Astellas Pharma, Tsukuba, Ibaraki, Japan; Department of Pediatrics, McMaster University, Ontario, Canada; Exerkine Corporation, Hamilton, Canada; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA. DOI - https://doi.org/10.18632/aging.204435 Corresponding author - Simon Melov - smelov@buckinstitute.org Abstract Aging is accompanied by a loss of muscle mass and function, termed sarcopenia, which causes numerous morbidities and economic burdens in human populations. Mechanisms implicated in age-related sarcopenia or frailty include inflammation, muscle stem cell depletion, mitochondrial dysfunction, and loss of motor neurons, but whether there are key drivers of sarcopenia are not yet known. To gain deeper insights into age-related muscle loss, we performed transcriptome profiling on lower limb muscle biopsies from 72 young, elderly, and frail human subjects using bulk RNA-seq (N = 72) and single-nuclei RNA-seq (N = 17). This combined approach revealed changes in gene expression that occur with age and frailty in multiple cell types comprising mature skeletal muscle. Notably, we found increased expression of the genes MYH8 and PDK4, and decreased expression of the gene IGFN1, in aged muscle. We validated several key genes changes in fixed human muscle tissue using digital spatial profiling. We also identified a small population of nuclei that express CDKN1A, present only in aged samples, consistent with p21cip1-driven senescence in this subpopulation. Overall, our findings identify unique cellular subpopulations in aged and sarcopenic skeletal muscle, which will facilitate the development of new therapeutic strategies to combat age-related frailty. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204435 Press release - https://www.aging-us.com/news_room/single-nuclei-profiling-identifies-cell-specific-markers-of-skeletal-muscle-aging-frailty-and-senescence Keywords - aging, transcriptomics, muscle, senescence, sarcopenia About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM