{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:27:05Z","timestamp":1790839625864,"version":"4.1.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T00:00:00Z","timestamp":1608076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>Cellular senescence is implicated in several lines of aging-related disorders. However, the potential molecular mechanisms by which cellular senescence modulates age-related pathologies remain largely unexplored. Herein, we report that the density of sympathetic fibers (SFs) is significantly elevated in naturally aged mouse tissues and human colon adenoma tissues compared to the SFs densities in the corresponding young mouse tissues and human non-lesion colon tissues. A dorsal root ganglion (DRG)-human diploid fibroblast coculture assay revealed that senescent cells promote the outgrowth of SFs, indicating that the senescent cells induce recruitment of SFs <jats:italic>in vitro<\/jats:italic>. Additionally, subcutaneous transplantation of 2BS fibroblasts in nude mice shows that transplanted senescent 2BS fibroblasts promote SFs infiltration. Intra-articular senolytic molecular injection can reduce SFs density and inhibit SFs infiltration caused by senescent cells in osteoarthritis (OA), suggesting senescent cells promote the infiltration of SFs <jats:italic>in vivo<\/jats:italic> in aged tissues. Notably, the elevated level of SFs contributes to impaired cognitive function in naturally aged mice, which can be reversed by treatment with propranolol hydrochloride, a non-selective \u03b2 receptor blocker that inhibits sympathetic nerve activity (SNA) by blocking non-selective \u03b2 receptors. Additionally, 6-hydroxydopamine (6-OHDA)-induced sympathectomy improved hepatic sympathetic overactivity mediated hepatic steatosis in high fat diet (HFD)-fed <jats:italic>APOE<\/jats:italic> knockout mice (APOE<jats:sup>\u2212\/\u2212<\/jats:sup> mice) by reducing hepatic SNA. Taken together, this study concludes that senescent cell-secreted netrin-1 mediated SFs outgrowth and infiltration, which contributes to aging-related disorders, suggesting that clearing senescent cells or inhibiting SNA is a promising therapeutic strategy for improving sympathetic nervous system (SNS) hyperactivity-induced aging-related pathologies.<\/jats:p>","DOI":"10.3389\/fnagi.2020.507140","type":"journal-article","created":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T13:49:00Z","timestamp":1610286540000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Senescent Cell-Secreted Netrin-1 Modulates Aging-Related Disorders by Recruiting Sympathetic Fibers"],"prefix":"10.3389","volume":"12","author":[{"given":"Ai Qing","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao Jia","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You De","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi Xiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze Bin","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/nature10600","article-title":"Clearance of p16INK4A-positive senescent cells delays ageing-associated disorders","volume":"479","author":"Baker","year":"2011","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e45069","DOI":"10.1371\/journal.pone.0045069","article-title":"Astrocyte senescence as a component of Alzheimer\u2019s disease","volume":"7","author":"Bhat","year":"2012","journal-title":"PLoS One"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1172\/JCI119316","article-title":"Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage","volume":"99","author":"Billinghurst","year":"1997","journal-title":"J. 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