Photo-Downregulation of SIRT4 Mitigates Aging in Mice by Enhancing H3K9ac via Fatty Acid Metabolism

This study demonstrates that periodic exposure to red light can mitigate aging in mice by enhancing histone H3 Lys9 acetylation (H3K9ac) through the modulation of fatty acid metabolism. Red light exposure reduces SIRT4 protein levels in keratinocytes, which activates glycolysis, fatty acid metabolism, and the TCA cycle. The decrease in SIRT4 enhances mitochondrial fatty acid oxidation and activates SIRT1, which alleviates its inhibition on PPAR-α, leading to increased expression of lipid metabolism-related genes. This results in the accumulation of acetyl-CoA, increased H3K9ac levels, and altered expression of senescence-related genes, effectively reducing cellular aging through the regulation of metabolism, inflammation, and gene expression.