Impaired Mechanosensitivity in Aged Muscle Stem Cells

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Aging (Aging-US)

Aging (Aging-US) published this priority research paper as the cover for Volume 14, Issue 1, entitled, "Reduced growth rate of aged muscle stem cells is associated with impaired mechanosensitivity" by researchers from the Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam 1081 HZ, The Netherlands; Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam 1081 LA, The Netherlands; Sorbonne Université, INSERM UMRS974, Center for Research in Myology, Paris 75013, France; Department of Physiology, Amsterdam University Medical Center VUmc, Amsterdam Cardiovascular Sciences, Amsterdam 1081 HZ, The Netherlands; Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve 1348, Belgium; Exercise Physiology Research Group, Department of Movement Sciences, KU Leuven, Leuven 3001, Belgium; Faculty of Medicine and Pharmacy, NeuroMyoGène UCBL-CNRS UMR 5310, INSERM U1217, Lyon 69008, France. DOI - https://doi.org/10.18632/aging.203830 Correspondence to - Richard T. Jaspers - r.t.jaspers@vu.nl Abstract: Aging-associated muscle wasting and impaired regeneration are caused by deficiencies in muscle stem cell (MuSC) number and function. We postulated that aged MuSCs are intrinsically impaired in their responsiveness to omnipresent mechanical cues through alterations in MuSC morphology, mechanical properties, and number of integrins, culminating in impaired proliferative capacity. Here we show that aged MuSCs exhibited significantly lower growth rate and reduced integrin-α7 expression as well as lower number of phospho-paxillin clusters than young MuSCs. Moreover, aged MuSCs were less firmly attached to matrigel-coated glass substrates compared to young MuSCs, as 43% of the cells detached in response to pulsating fluid shear stress (1 Pa). YAP nuclear localization was 59% higher than in young MuSCs, yet YAP target genes Cyr61 and Ctgf were substantially downregulated. When subjected to pulsating fluid shear stress, aged MuSCs exhibited reduced upregulation of proliferation-related genes. Together these results indicate that aged MuSCs exhibit impaired mechanosensitivity and growth potential, accompanied by altered morphology and mechanical properties as well as reduced integrin-α7 expression. Aging-associated impaired muscle regenerative capacity and muscle wasting is likely due to aging-induced intrinsic MuSC alterations and dysfunctional mechanosensitivity. Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.203830 Keywords - aging, mechanosensitivity, muscle stem cell, proliferation, YAP signaling 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 http://www.Aging-US.com​​ or 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/ Aging-US is published by Impact Journals, LLC: http://www.ImpactJournals.com​​ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM