Sirtuin 6 overexpression rejuvenates liver DNA by reversing aging-related chromatin changes

SIRT6 overexpression, a histone deacetylase protein, reverses the structural chromatin changes that characterize hepatic aging, according to a multi-omics study combining ATAC-seq analysis, methylome profiling, and RNA sequencing in male murine livers. Aging typically increases aberrant chromatin accessibility, triggering inflammation and metabolic decline, but SIRT6 intervention inverts this pattern. Researchers identified that H3K9ac acetylation (but not H3K56ac) drives aberrant accessibility during aging, and SIRT6 can selectively suppress this effect. AAV-mediated SIRT6 administration in aged mice not only slowed age-related chromatin changes but actively restored chromatin architecture to a state comparable to young animals. For the longevity-curious, this reveals a potentially reversible epigenetic mechanism through targeted intervention, opening new therapeutic pathways beyond partial reprogramming.