Attenuating Cholinergic Transmission Increases the Number of Satellite Cells and Preserves Muscle Mass in Old Age

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dc.contributor.authorVaughan, Sydney K.en
dc.contributor.authorSutherland, Natalia M.en
dc.contributor.authorValdez, Gregorioen
dc.contributor.departmentBiological Sciencesen
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.date.accessioned2020-02-18T18:49:52Zen
dc.date.available2020-02-18T18:49:52Zen
dc.date.issued2019-09-24en
dc.description.abstractIn addition to driving contraction of skeletal muscles, acetylcholine (ACh) acts as an anti-synaptogenic agent at neuromuscular junctions (NMJs). Previous studies suggest that aging is accompanied by increases in cholinergic activity at the NMJ, which may play a role in neuromuscular degeneration. In this study, we hypothesized that moderately and chronically reducing ACh could attenuate the deleterious effects of aging on NMJs and skeletal muscles. To test this hypothesis, we analyzed NMJs and muscle fibers from heterozygous transgenic mice with reduced expression of the vesicular ACh transporter (VAChT; VKDHet), which present with approximately 30% less synaptic ACh compared to control mice. Because ACh is constitutively decreased in VKDHet, we first analyzed developing NMJs and muscle fibers. We found no obvious morphological or molecular differences between NMJs and muscle fibers of VKDHet and control mice during development. In contrast, we found that moderately reducing ACh has various effects on adult NMJs and muscle fibers. VKDHet mice have significantly larger NMJs and muscle fibers compared to age-matched control mice. They also present with reduced expression of the pro-atrophy gene, Foxo1, and have more satellite cells in skeletal muscles. These molecular and cellular features may partially explain the increased size of NMJs and muscle fibers. Thus, moderately reducing ACh may be a therapeutic strategy to prevent the loss of skeletal muscle mass that occurs with advancing age.en
dc.description.notesGrants from the National Institute on Aging (NI grants R01AG05545 and R56AG051501) and the National Institute of Neurological Disorders and Stroke (NINDS grant R21NS106313) supported this study.en
dc.description.sponsorshipNational Institute on Aging (NI) [R01AG05545, R56AG051501]; National Institute of Neurological Disorders and Stroke (NINDS)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [R21NS106313]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3389/fnagi.2019.00262en
dc.identifier.issn1663-4365en
dc.identifier.other262en
dc.identifier.pmid31616286en
dc.identifier.urihttp://hdl.handle.net/10919/96925en
dc.identifier.volume11en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectcholinergic transmissionen
dc.subjectVAChTen
dc.subjectPax7en
dc.subjectAgingen
dc.subjectsynapseen
dc.subjectsarcopeniaen
dc.titleAttenuating Cholinergic Transmission Increases the Number of Satellite Cells and Preserves Muscle Mass in Old Ageen
dc.title.serialFrontiers in Aging Neuroscienceen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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