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This non\u2010lethal phenotype makes the hair follicle and its pigment system an attractive model for investigating mechanisms that contribute to tissue aging and therapeutic strategies to combat this process. One potential combination therapeutic is RT1640, which is comprised of two drugs that are known to stimulate hair growth (cyclosporine A [CsA] and minoxidil), along with RT175, a non\u2010immunosuppressive immunophilin ligand that is implicated in tissue regeneration. Using the ionizing radiation\u2010induced acute mouse model of hair graying, we demonstrate that RT1640, over CsA alone, promotes regeneration of the hair pigment system during and following treatment. In non\u2010irradiated mice, RT1640 is also physiologically active and successfully speeds hair growth and expands the McSC pool. It appears that this effect relies on the combined activities of the three drugs within RT1640 to simultaneously activate hair growth and McSCs as RT175 alone was insufficient to induce hair cycling in vivo, yet sufficient to drive the upregulation of the melanogenic program in vitro. This study sets the stage for further investigation into RT1640 and its components in McSC biology and, ultimately, melanocyte hypopigmentary disorders associated with disease and aging.<\/jats:p>","DOI":"10.1111\/pcmr.12913","type":"journal-article","created":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T19:09:05Z","timestamp":1594494545000},"page":"89-100","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Topical RT1640 treatment effectively reverses gray hair and stem cell loss in a mouse model of radiation\u2010induced canities"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7470-6976","authenticated-orcid":false,"given":"Zoya T.","family":"Anderson","sequence":"first","affiliation":[{"name":"Department of Biology University of Alabama at Birmingham Birmingham AL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4778-2743","authenticated-orcid":false,"given":"Joseph W.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Department of Biology University of Alabama at Birmingham Birmingham AL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4189-0612","authenticated-orcid":false,"given":"Misgana I.","family":"Idris","sequence":"additional","affiliation":[{"name":"Department of Biology University of Alabama at Birmingham Birmingham AL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyrene M.","family":"Villavicencio","sequence":"additional","affiliation":[{"name":"Department of Biology University of Alabama at Birmingham Birmingham AL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giang","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Biology University of Alabama at Birmingham Birmingham AL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaelyn","family":"Cowart","sequence":"additional","affiliation":[{"name":"Department of Biology University of Alabama at Birmingham Birmingham AL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David E.","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Rivertown Therapeutics, Inc Dobbs Ferry NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6223-1611","authenticated-orcid":false,"given":"Melissa L.","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Biology University of Alabama at Birmingham Birmingham AL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,7,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0738-081X(88)90086-7"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2003.10.013"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19030691"},{"key":"e_1_2_8_5_1","volume-title":"Women, aging, and beauty culture: Navigating the social perils of looking old","author":"Clarke L. 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