{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:33:05Z","timestamp":1790184785060,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002338","name":"Ministry of Education of China","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002338","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003512","name":"State Administration of Foreign Experts Affairs","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003512","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/055gka453","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Chronic ultraviolet B (UVB) radiation drives cutaneous photoaging\u2014clinically manifesting as erythema, edema, scaling, deep wrinkling, loss of elasticity, and barrier disruption\u2014through mitochondrial reactive oxygen species (mtROS) overproduction and quality-control failure. Here we identify \u03b1-ketoglutarate (AKG; also known as 2-oxoglutarate), a TCA-cycle intermediate and essential co-substrate for \u03b1-ketoglutarate-dependent dioxygenases (\u03b1-KGDDs), as a metabolic corrector of mitochondrial redox homeostasis in UVB-induced photoaging. In a 10-week chronic UVB SKH1 hairless mouse model, microneedle-assisted transdermal delivery of AKG dose-dependently attenuated macroscopic erythema, scaling, and erosive lesions, restored skin barrier function and dermal elasticity, preserved epidermal\u2013dermal architecture, and protected collagen and elastic fiber integrity, with efficacy comparable to all-trans retinoic acid. Mechanistically, AKG reactivated \u03b1-KGDD\/prolyl hydroxylase (PHD) catalytic function and promoted proteasomal clearance of aberrantly stabilized HIF-1\u03b1 under normoxia; this was accompanied by restored AMPK Thr172 phosphorylation downstream of constitutive LKB1 and recovery of PGC-1\u03b1-driven mitochondrial biogenesis. AKG preferentially attenuated mitochondrial superoxide over total cellular ROS through a co-substrate-mediated mechanism distinct from direct radical scavenging, and its protective effects were largely abrogated by DMOG (an \u03b1-KGDD inhibitor) or compound C (an AMPK inhibitor). These findings position AKG, delivered via microneedle-assisted topical application, as a candidate metabolite-based intervention targeting the \u03b1-KGDD\/HIF-1\u03b1\/AMPK axis for photoaging.<\/jats:p>","DOI":"10.3390\/antiox15070845","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T14:56:42Z","timestamp":1783349802000},"page":"845","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Alpha-Ketoglutarate Attenuates UVB-Induced Skin Photoaging by Restoring Mitochondrial Redox Homeostasis"],"prefix":"10.3390","volume":"15","author":[{"given":"Wenrui","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijia","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1016\/j.jid.2020.12.011","article-title":"Environmentally-Induced (Extrinsic) Skin Aging: Exposomal Factors and Underlying Mechanisms","volume":"141","author":"Krutmann","year":"2021","journal-title":"J. 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