Journal of photochemistry and photobiology. B, BiologyApr 25, 2026

SIRT1 helps prevent skin aging from UVA light by reducing oxidative stress and modifying a key protective protein in skin cells

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 26, 2026

Abstract

Repetitive ultraviolet A (UVA) irradiation downregulates both SIRT1 and FOXO3a in human skin.

Chronic oxidative stress and cellular senescence were modeled in human skin and dermal fibroblasts after UVA exposure.
Activation of SIRT1 with SRT1720 reduced oxidative stress, DNA damage, and extracellular matrix degradation caused by UVA.
SIRT1 was found to stabilize FOXO3a, allowing it to enhance the expression of key antioxidant genes.
Knockdown of FOXO3a eliminated the protective effects of SIRT1 activation, indicating its crucial role in the process.
The study identifies the SIRT1-FOXO3a pathway as key in regulating antioxidant defense and maintaining skin structure.

Simplified

The molecular mechanisms by which silent information regulator 1 (SIRT1) protects against skin photoaging remain incompletely defined. This study demonstrates that repetitive ultraviolet A (UVA) irradiation downregulates both SIRT1 and its transcription factor target FOXO3a in human skin and dermal fibroblasts (HDFs), establishing a chronic oxidative stress and senescence model. We found that pharmacological activation of SIRT1 with SRT1720 significantly mitigated UVA-induced damage, reducing oxidative stress, DNA damage (8-OHdG), cellular senescence, and extracellular matrix degradation. Mechanistically, SIRT1 deacetylated and stabilized Forkhead box O3 (FOXO3a), enabling it to transcriptionally upregulate key antioxidant defense genes (SOD2, HO-1, CAT). Crucially, all protective effects of SIRT1 activation were completely abolished upon FOXO3a knockdown, genetically establishing FOXO3a as the essential downstream effector. Our results delineate the SIRT1-FOXO3a deacetylation axis as a central regulatory pathway that coordinates antioxidant defense and ECM homeostasis, highlighting its potential as a precise therapeutic target for mitigating skin photoaging.

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Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

SIRT1 helps prevent skin aging from UVA light by reducing oxidative stress and modifying a key protective protein in skin cells

Abstract

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Competing interests

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