The Journal of dermatologyAug 25, 2026

Resveratrol May Reduce Age-Related Skin Thinning in Mice by Activating SIRT1

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Aug 26, 2026

Abstract

Epidermal and dermal thicknesses were significantly reduced in 60-week-old mice compared with 20-week-old mice.

Dietary resveratrol (0.4 g/kg diet) administered from 28 weeks of age for 32 weeks attenuated age-related skin thinning in mice.
The number of skin cells actively dividing (Ki67-positive cells) decreased in aged mice but was restored by resveratrol treatment.
Resveratrol treatment significantly reduced the number of acetyl-lysine-positive cells, indicating enhanced activity of the SIRT1 protein.
Aged mice showed increased areas of specific proteins (MMP-9 and MMP-13) linked to skin degradation, which were not observed in resveratrol-treated aged mice.
SIRT1 knockdown in human skin cells increased markers of cellular aging, suggesting a role of SIRT1 in cellular senescence.

Simplified

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.

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Resveratrol May Reduce Age-Related Skin Thinning in Mice by Activating SIRT1

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