{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:07:40Z","timestamp":1788962860436,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,7]]},"group-title":"Developmental Biology","reference-count":85,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006034","name":"University of Southern California","doi-asserted-by":"crossref","award":["startup funds"],"award-info":[{"award-number":["startup funds"]}],"id":[{"id":"10.13039\/100006034","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000900","name":"California Institute for Regenerative Medicine","doi-asserted-by":"crossref","award":["EDUC4-12756"],"award-info":[{"award-number":["EDUC4-12756"]}],"id":[{"id":"10.13039\/100000900","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000900","name":"California Institute for Regenerative Medicine","doi-asserted-by":"crossref","award":["EDUC5-13853"],"award-info":[{"award-number":["EDUC5-13853"]}],"id":[{"id":"10.13039\/100000900","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["R01 AG076433"],"award-info":[{"award-number":["R01 AG076433"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["U54 AG099000"],"award-info":[{"award-number":["U54 AG099000"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["F31AG084279"],"award-info":[{"award-number":["F31AG084279"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["T32AG052374"],"award-info":[{"award-number":["T32AG052374"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["T32 5T32HD060549-15"],"award-info":[{"award-number":["T32 5T32HD060549-15"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Cancer Institute","award":["SFI-AN-NC-AB-Research-00018042"],"award-info":[{"award-number":["SFI-AN-NC-AB-Research-00018042"]}]},{"name":"National Cancer Institute","award":["1R01CA267108"],"award-info":[{"award-number":["1R01CA267108"]}]},{"name":"National Cancer Institute","award":["1P01CA278732"],"award-info":[{"award-number":["1P01CA278732"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Peripheral innervation declines with age, but whether this process is sexually dimorphic and whether it reflects neuronal degeneration or deterioration of nerve\u2013target interactions remain unclear. Using mouse skin as a defined neuroeffector system, we show that sympathetic aging is strongly sexually dimorphic, with greater denervation in aged males. Skin-projecting sympathetic neurons remain intact, indicating that denervation reflects distal axon withdrawal rather than neuronal loss. Nerve\u2013target interactions and the arrector pili muscle niche deteriorate with age, predominantly in males. Aged sympathetic neurons retain NGF responsiveness, and restoring NGF within arrector pili muscles promotes sympathetic reinnervation and hair regeneration in aged males. Genetic and endocrine models show that divergent aging trajectories are associated with gonadal rather than chromosomal sex and are attenuated by early gonadectomy. Together, these findings identify sympathetic aging as a reversible, sexually dimorphic distal axonopathy shaped by the target environment and gonadal influences.<\/jats:p>","DOI":"10.64898\/2026.09.03.748995","type":"posted-content","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T21:55:36Z","timestamp":1788818136000},"source":"Crossref","is-referenced-by-count":0,"title":["Reversible, Sexually Dimorphic Sympathetic Aging: Distal Axon Withdrawal Shaped by Prepubertal Gonadal Influences"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2662-7883","authenticated-orcid":false,"given":"Gabriella Rita","family":"Pangilinan","sequence":"first","affiliation":[{"name":"Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sagar","family":"Patil","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Mires","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Bogomilova","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine","family":"Tilley","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tali","family":"Goldkorn","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra J.","family":"McGill","sequence":"additional","affiliation":[{"name":"USC Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Ballou","sequence":"additional","affiliation":[{"name":"Department of Medicine, Department of Biomedical Sciences, and Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Cedars-Sinai Health Sciences University, Los Angeles, CA 90048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine, Department of Biomedical Sciences, and Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Cedars-Sinai Health Sciences University, Los Angeles, CA 90048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Unmesh","family":"Jadhav","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9r\u00e9nice A.","family":"Benayoun","sequence":"additional","affiliation":[{"name":"USC Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA"},{"name":"Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USA"},{"name":"Department of Cancer Biology, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA"},{"name":"Epigenetics and Gene Regulation Program, USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia","family":"Shwartz","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA"},{"name":"USC Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA"},{"name":"Department of Dermatology, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026090906101072000_2026.09.03.748995v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.06.008"},{"key":"2026090906101072000_2026.09.03.748995v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-021-00489-x"},{"key":"2026090906101072000_2026.09.03.748995v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2022.04.005"},{"key":"2026090906101072000_2026.09.03.748995v1.4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-120320-032429"},{"key":"2026090906101072000_2026.09.03.748995v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0030-x"},{"key":"2026090906101072000_2026.09.03.748995v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2013.09.002"},{"key":"2026090906101072000_2026.09.03.748995v1.7","doi-asserted-by":"publisher","DOI":"10.1002\/ar.25015"},{"key":"2026090906101072000_2026.09.03.748995v1.8","doi-asserted-by":"publisher","DOI":"10.1126\/science.ade4961"},{"key":"2026090906101072000_2026.09.03.748995v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2026.117126"},{"key":"2026090906101072000_2026.09.03.748995v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2018.01.047"},{"key":"2026090906101072000_2026.09.03.748995v1.11","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.63425"},{"key":"2026090906101072000_2026.09.03.748995v1.12","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-019-02082-w"},{"key":"2026090906101072000_2026.09.03.748995v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-98565-w"},{"key":"2026090906101072000_2026.09.03.748995v1.14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2010.00271.x"},{"key":"2026090906101072000_2026.09.03.748995v1.15","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12871"},{"key":"2026090906101072000_2026.09.03.748995v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(01)00508-9"},{"key":"2026090906101072000_2026.09.03.748995v1.17","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c140005"},{"key":"2026090906101072000_2026.09.03.748995v1.18","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.120.15208"},{"key":"2026090906101072000_2026.09.03.748995v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2021.01.001"},{"key":"2026090906101072000_2026.09.03.748995v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.01.014"},{"key":"2026090906101072000_2026.09.03.748995v1.21","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4376"},{"key":"2026090906101072000_2026.09.03.748995v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00774-2"},{"key":"2026090906101072000_2026.09.03.748995v1.23","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00859.2006"},{"key":"2026090906101072000_2026.09.03.748995v1.24","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90378-6"},{"key":"2026090906101072000_2026.09.03.748995v1.25","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19971103)387:4<489::AID-CNE2>3.0.CO;2-Z"},{"key":"2026090906101072000_2026.09.03.748995v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-021-00523-y"},{"key":"2026090906101072000_2026.09.03.748995v1.27","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.12-04-01454.1992"},{"key":"2026090906101072000_2026.09.03.748995v1.28","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.28.061604.135659"},{"key":"2026090906101072000_2026.09.03.748995v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1326"},{"key":"2026090906101072000_2026.09.03.748995v1.30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1719548115"},{"key":"2026090906101072000_2026.09.03.748995v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2021.05.031"},{"key":"2026090906101072000_2026.09.03.748995v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.06.031"},{"key":"2026090906101072000_2026.09.03.748995v1.33","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-025-01139-z"},{"key":"2026090906101072000_2026.09.03.748995v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.113674"},{"key":"2026090906101072000_2026.09.03.748995v1.35","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00639.2024"},{"key":"2026090906101072000_2026.09.03.748995v1.36","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0166-14.2014"},{"key":"2026090906101072000_2026.09.03.748995v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2007.03.007"},{"key":"2026090906101072000_2026.09.03.748995v1.38","doi-asserted-by":"crossref","unstructured":"J\u00e4nig, W. Functional Anatomy of the Peripheral Sympathetic and Parasympathetic Systems., 9\u201333 (Cambridge University Press, 2022).","DOI":"10.1017\/9781108778411.005"},{"key":"2026090906101072000_2026.09.03.748995v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.09.021"},{"key":"2026090906101072000_2026.09.03.748995v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/S1566-0702(01)00372-1"},{"key":"2026090906101072000_2026.09.03.748995v1.41","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1901720117"},{"key":"2026090906101072000_2026.09.03.748995v1.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.09.015"},{"key":"2026090906101072000_2026.09.03.748995v1.43","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-0922-4"},{"key":"2026090906101072000_2026.09.03.748995v1.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2020.11.002"},{"key":"2026090906101072000_2026.09.03.748995v1.45","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2011.01356.x"},{"key":"2026090906101072000_2026.09.03.748995v1.46","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201801002R"},{"key":"2026090906101072000_2026.09.03.748995v1.47","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00501.2005"},{"key":"2026090906101072000_2026.09.03.748995v1.48","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-68748-9_7"},{"key":"2026090906101072000_2026.09.03.748995v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2013.07.019"},{"key":"2026090906101072000_2026.09.03.748995v1.50","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00580.2016"},{"key":"2026090906101072000_2026.09.03.748995v1.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2014.11.009"},{"key":"2026090906101072000_2026.09.03.748995v1.52","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-003-0027-8"},{"key":"2026090906101072000_2026.09.03.748995v1.53","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00057.2014"},{"key":"2026090906101072000_2026.09.03.748995v1.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2020.09.021"},{"key":"2026090906101072000_2026.09.03.748995v1.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2008.11.001"},{"key":"2026090906101072000_2026.09.03.748995v1.56","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-014-0952-0"},{"key":"2026090906101072000_2026.09.03.748995v1.57","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00506.2010"},{"key":"2026090906101072000_2026.09.03.748995v1.58","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.212753"},{"key":"2026090906101072000_2026.09.03.748995v1.59","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1681.1999.02995.x"},{"key":"2026090906101072000_2026.09.03.748995v1.60","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-77932-4_9"},{"key":"2026090906101072000_2026.09.03.748995v1.61","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.15702"},{"key":"2026090906101072000_2026.09.03.748995v1.62","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2013.08.015"},{"key":"2026090906101072000_2026.09.03.748995v1.63","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a040840"},{"key":"2026090906101072000_2026.09.03.748995v1.64","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020107135"},{"key":"2026090906101072000_2026.09.03.748995v1.65","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-023-00662-3"},{"key":"2026090906101072000_2026.09.03.748995v1.66","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1195272"},{"key":"2026090906101072000_2026.09.03.748995v1.67","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtv.2016.03.002"},{"key":"2026090906101072000_2026.09.03.748995v1.68","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2022-0183"},{"key":"2026090906101072000_2026.09.03.748995v1.69","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2008.00372.x"},{"key":"2026090906101072000_2026.09.03.748995v1.70","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.4A6585.2005"},{"key":"2026090906101072000_2026.09.03.748995v1.71","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(03)46031-7"},{"key":"2026090906101072000_2026.09.03.748995v1.72","doi-asserted-by":"publisher","DOI":"10.1113\/JP284739"},{"key":"2026090906101072000_2026.09.03.748995v1.73","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2013.06.005"},{"key":"2026090906101072000_2026.09.03.748995v1.74","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2026.01.010"},{"key":"2026090906101072000_2026.09.03.748995v1.75","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2025.12.994"},{"key":"2026090906101072000_2026.09.03.748995v1.76","doi-asserted-by":"publisher","DOI":"10.1126\/science.adv5974"},{"key":"2026090906101072000_2026.09.03.748995v1.77","doi-asserted-by":"publisher","DOI":"10.3389\/frhem.2025.1525132"},{"key":"2026090906101072000_2026.09.03.748995v1.78","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.211334"},{"key":"2026090906101072000_2026.09.03.748995v1.79","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.102447"},{"key":"2026090906101072000_2026.09.03.748995v1.80","doi-asserted-by":"publisher","DOI":"10.1002\/dev.22085"},{"key":"2026090906101072000_2026.09.03.748995v1.81","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-021-01138-x"},{"key":"2026090906101072000_2026.09.03.748995v1.82","doi-asserted-by":"publisher","DOI":"10.1037\/dev0001903"},{"key":"2026090906101072000_2026.09.03.748995v1.83","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-026-72381-0"},{"key":"2026090906101072000_2026.09.03.748995v1.84","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52640-8"},{"key":"2026090906101072000_2026.09.03.748995v1.85","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2026.02.027"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.03.748995","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T13:10:21Z","timestamp":1788959421000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.03.748995"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":85,"URL":"https:\/\/doi.org\/10.64898\/2026.09.03.748995","relation":{},"subject":[],"published":{"date-parts":[[2026,9,7]]},"subtype":"preprint"}}