{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:13:07Z","timestamp":1788221587325,"version":"build-2803163510"},"reference-count":30,"publisher":"American Chemical Society (ACS)","issue":"33","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mitochondrial dysfunction contributes to skin aging by limiting cellular energy supply, shifting redox balance, and amplifying oxidative injury, which together favor extracellular matrix breakdown and loss of tissue mechanics. Vitamin K2 (menaquinone-7; MK-7) has been proposed to support mitochondrial electron transport, yet its bioenergetic activity in the skin and its effects on aging-related outcomes remain insufficiently characterized. To evaluate whether MK-7 can improve mitochondrial bioenergetics in skin-relevant cells under oxidative stress and whether these effects translate into quantifiable anti-aging benefits in a controlled human study. In vitro, human skin cells were exposed to UVA or hydrogen peroxide to model oxidative stress and then treated with MK-7. ATP content, NAD+\/NADH ratio, mitochondrial membrane potential (\u0394\u03a8m), mitochondrial DNA (mtDNA) copy number, respiratory chain complex activities (I\u2013V), and senescence-associated secretory phenotype (SASP) expression were assessed using established assays. In vivo, a randomized, double-blind, split-face\/neck, vehicle-controlled trial enrolled women aged 35\u201360 years (n = 30 completers). Participants applied a 0.05% MK-7 face-and-neck cream to one randomized side and placebo to the contralateral side twice daily for 8 weeks. Wrinkles\/roughness, elasticity, and sagging were instrumentally quantified at baseline and weeks 2, 4, and 8. MK-7 increased ATP production, elevated the NAD+\/NADH ratio, restored \u0394\u03a8m, preserved mtDNA copy number under oxidative challenge, enhanced activities of multiple respiratory complexes, and reduced UVA-induced SASP marker expression. In human efficacy evaluations, MK-7 produced significant improvements versus placebo in wrinkle roughness on face and neck, improved elasticity parameters, and attenuated sagging over 8 weeks. MK-7 was associated with improved mitochondrial bioenergetic readouts in vitro and measurable anti-aging effects in a split-face\/neck study, supporting further development of mitochondrial targeting approaches for skin aging.<\/jats:p>","DOI":"10.1021\/acsomega.6c03314","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T22:01:26Z","timestamp":1786744886000},"page":"49613-49625","source":"Crossref","is-referenced-by-count":0,"title":["Topical Menaquinone-7\n(Vitamin K2, MK-7) as\na Mitochondrial Bioenergetic Activator for Skin Anti-Aging: Mechanistic\nEvidence in Skin Cells and a Randomized Split-Face\/Neck Study"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4520-0558","authenticated-orcid":true,"given":"He","family":"Huang","sequence":"first","affiliation":[{"name":"Nanjing Ascend Biotech Co., Ltd. , Room 1805, Zhaoyin Building, No. 199, Lushan Road , Jianye District, , ,","place":["Nanjing, Jiangsu, China, 210019"]},{"name":"Nanjing University of Technology , , No. 5, Xin Mo Fan Road , , ,","place":["Nanjing, Jiangsu, China, 210009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruijing","family":"Wei","sequence":"additional","affiliation":[{"name":"Proya Cosmetics Co., Ltd. , PROYA Building, No. 588, Xixi Road, Liuxia Street , Xihu District, , ,","place":["Hangzhou, Zhejiang, China, 310023"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxiao","family":"Xu","sequence":"additional","affiliation":[{"name":"Nanjing Ascend Biotech Co., Ltd. , Room 1805, Zhaoyin Building, No. 199, Lushan Road , Jianye District, , ,","place":["Nanjing, Jiangsu, China, 210019"]},{"name":"Nanjing University of Technology , , No. 5, Xin Mo Fan Road , , ,","place":["Nanjing, Jiangsu, China, 210009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5866-4456","authenticated-orcid":true,"given":"Chen","family":"Liu","sequence":"additional","affiliation":[{"name":"Nanjing Ascend MegaBio Technology Co., Ltd. , Room 1805, Zhaoyin Building, No. 199, Lushan Road , Jianye District, , ,","place":["Nanjing, Jiangsu, China, 210019"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Nanjing Ascend Mercedes Medical Technology Co., Ltd. , Room 503, Building B, No. 606, Ningliu Road , Jiangbei New District, , ,","place":["Nanjing, Jiangsu, China, 210044"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Li","sequence":"additional","affiliation":[{"name":"Proya Cosmetics Co., Ltd. , PROYA Building, No. 588, Xixi Road, Liuxia Street , Xihu District, , ,","place":["Hangzhou, Zhejiang, China, 310023"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijing","family":"Wang","sequence":"additional","affiliation":[{"name":"Proya Cosmetics Co., Ltd. , PROYA Building, No. 588, Xixi Road, Liuxia Street , Xihu District, , ,","place":["Hangzhou, Zhejiang, China, 310023"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"issue":"8","key":"2026083119145314600_cit1","doi-asserted-by":"publisher","first-page":"2043","DOI":"10.1016\/j.cell.2025.03.011","article-title":"From geroscience to\nprecision geromedicine: understanding and managing aging","volume":"188","author":"Kroemer","year":"2025","journal-title":"Cell"},{"issue":"7","key":"2026083119145314600_cit2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042357","article-title":"Age-associated changes in oxidative stress and NAD+ metabolism in human tissue","volume":"7","author":"Massudi","year":"2012","journal-title":"PLoS One"},{"issue":"6","key":"2026083119145314600_cit3","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1038\/s41419-020-2649-z","article-title":"Mitochondria in skin health, aging,\nand disease","volume":"11","author":"Sreedhar","year":"2020","journal-title":"Cell Death Dis."},{"key":"2026083119145314600_cit4","doi-asserted-by":"publisher","first-page":"101917","DOI":"10.1016\/j.arr.2023.101917","article-title":"The role of mitochondrial\nquality surveillance in skin aging: focus on mitochondrial dynamics,\nbiogenesis, and mitophagy","volume":"87","author":"Zhang","year":"2023","journal-title":"Ageing Res. Rev."},{"issue":"5","key":"2026083119145314600_cit5","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.3390\/ijms26051803","article-title":"Role of mitochondrial\ndynamics in skin homeostasis:\nan update","volume":"26","author":"Quan","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"2026083119145314600_cit6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2018\/6354680","article-title":"Age-dependent loss of mitochondrial\nfunction in epithelial tissue can be reversed by coenzyme Q10","volume":"2018","author":"Schniertshauer","year":"2018","journal-title":"J. Aging Res."},{"issue":"6","key":"2026083119145314600_cit7","doi-asserted-by":"publisher","first-page":"3303","DOI":"10.3390\/ijms25063303","article-title":"Dermatologic\nmanifestations of mitochondrial dysfunction: a review of the literature","volume":"25","author":"Natarelli","year":"2024","journal-title":"Int. J. Mol. 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