{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:55:31Z","timestamp":1790574931572,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Androgenetic alopecia (AGA) is the most common form of non\u2010scarring hair loss, driven by genetic factors and increased sensitivity of scalp hair follicles to dihydrotestosterone (DHT), which causes progressive miniaturization of dermal papilla cells and shortens the hair growth phase. The precise molecular pathogenesis of AGA remains incompletely understood. The study aimed to elucidate the regulatory mechanism between secreted frizzled\u2010related protein 2 (SFRP2) and follistatin\u2010like 1 (FSTL1), explore their impact on DHT\u2010induced mitochondrial dysfunction and senescence in dermal papilla cells (DPCs), elucidate the effect of the SFRP2\u2013FSTL1 axis on oxidative stress\u2010related DPCs changes, and identify new therapeutic targets for AGA treatment. In the study, SFRP2 was highly expressed in the DPCs of AGA patients. Knocking down SFRP2 improved hair regeneration and follicle morphology within AGA model mice, promoting proliferation, migration, and invasion of DPCs in\u00a0vitro. SFRP2 knockdown also alleviated inflammation, senescence, mitochondrial dysfunction, and oxidative stress. SFRP2 was found to bind to FSTL1, thereby promoting FSTL1 protein stability. Knocking down FSTL1 counteracted the negative effects of SFRP2 overexpression in\u00a0vitro. In conclusion, SFRP2 emerges as a critical regulator in AGA by promoting stability and activity of FSTL1, establishing a novel SFRP2\u2013FSTL1 axis that exacerbates DHT\u2010driven pathogenic changes in DPCs. These findings identify SFRP2 and FSTL1 as key mediators of androgen\u2010induced cellular dysfunction and suggest that disrupting this axis could offer a promising therapeutic strategy for slowing or reversing the progression of AGA.<\/jats:p>","DOI":"10.1111\/acel.70666","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T06:11:37Z","timestamp":1788588697000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Secreted Frizzled\u2010Related Protein 2 (\n                    <scp>SFRP2<\/scp>\n                    ) Induces Follistatin\u2010Like 1 (\n                    <scp>FSTL1<\/scp>\n                    ) to Regulate Dihydrotestosterone (\n                    <scp>DHT<\/scp>\n                    )\u2010Induced Dermal Papilla Cell Mitochondrial Dysfunction and Senescence"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7871-1644","authenticated-orcid":false,"given":"Youming","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Dermatology Center for Plastic and Reconstructive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1181-8738","authenticated-orcid":false,"given":"Qiong","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Dermatology Center for Plastic and Reconstructive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeyu","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Dermatology Center for Plastic and Reconstructive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2517-7166","authenticated-orcid":false,"given":"Xiaoxia","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Dermatology Center for Plastic and Reconstructive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3817-6696","authenticated-orcid":false,"given":"Yan","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Dermatology Center for Plastic and Reconstructive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1969-7316","authenticated-orcid":false,"given":"Danfeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Dermatology Center for Plastic and Reconstructive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianhong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Dermatology Center for Plastic and Reconstructive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4201-8498","authenticated-orcid":false,"given":"Yibin","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Dermatology Center for Plastic and Reconstructive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2020.111096"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25169031"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2019.10752"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.14536"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000530681"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010023\u201001880\u2010x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.18486"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.13487"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111247"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118227"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0923-1811(94)90045-0"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.116657"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/09546634.2022.2109567"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010023\u201043688\u20105"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741\u2010022\u201010262\u20106"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2026.150149"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929\u2010022\u201000800\u20107"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10522\u2010022\u201010002\u20101"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.5021\/ad.2014.26.1.79"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2022.121537"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2022.114231"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010023\u201005992\u20107"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.21783"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2024.04.004"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2023.05.004"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27196443"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/9265016"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010018\u20102805\u20100"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.15577"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25063303"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/jocd.14537"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.21881"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2025.119347"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/cimb43030097"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.12062"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1159\/000510152"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/ics.12736"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909501107"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2015.28"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555\u2010020\u201009941\u20103"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2022.114060"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753\u2010024\u201001972\u20100"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology13100842"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.724310"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.05.011"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28633"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1100045"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.3c00028"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70666","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70666","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70666","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:08:19Z","timestamp":1790572099000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70666"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":48,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/acel.70666"],"URL":"https:\/\/doi.org\/10.1111\/acel.70666","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2025-11-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70666"}}