Authors
Fuka Tamura, Iyori Nojima, Risa Kunimoto, Ryusuke Hosoda, Yuko Kuwabara, Keiko Kawakami, Kouhei Horimoto, Atsushi Kuno
Published in
The Journal of dermatology. Aug 24, 2026. Epub Aug 24, 2026.
Abstract
Aging is associated with thinning of the epidermis and dermis, leading to wrinkles, dryness, and impaired skin barrier function. Sirtuin-1 (SIRT1) is an NAD+-dependent protein deacetylase that suppresses cellular senescence and matrix metalloproteinase (MMP) expression, both of which contribute to skin thinning. Here, we investigated whether dietary resveratrol (RSV), a SIRT1 activator, mitigates age-related skin thinning in mice. Epidermal and dermal thicknesses were significantly reduced in 60-week-old (wo) mice compared with 20-wo mice, and these changes were attenuated by RSV administration (0.4 g/kg diet) from 28 weeks of age for 32 weeks. In the epidermis, the number of Ki67-positive cells decreased in aged mice but was restored by RSV treatment. Although RSV did not alter the number of SIRT1-positive cells, it significantly reduced the number of acetyl-lysine-positive cells, indicating enhanced SIRT1 activity. In the dermis, the immunopositive areas of MMP-9 and MMP-13 increased in aged mice, and these age-associated increases were not observed in RSV-treated aged mice. Phosphorylated SMAD2 levels decreased with age but were not affected by RSV. Furthermore, SIRT1 knockdown in human HaCaT keratinocytes increased p21 expression and senescence-associated β-galactosidase activity. Taken together, these findings suggest that the SIRT1 activator RSV ameliorates age-related skin thinning by suppressing cellular senescence in the epidermis and inhibiting dermal collagen degradation.
PMID:
42638272
Bibliographic data and abstract were imported from PubMed on 25 Aug 2026.
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