Longevity & AgingSIRT6 overexpression keeps aging mouse liver chromatin young and may even rewind it
Aging loosens chromatin in the liver, which is linked to rising inflammation and falling metabolic function. Researchers at Bar-Ilan University and the NIH examined male mouse livers using ATAC-seq, DNA methylation profiling, RNA-seq and ChIP-seq. In normal mice, chromatin became broadly more accessible with age. In mice overexpressing the histone deacetylase SIRT6, old livers stayed close to a young-like state. Inflammatory genes were dampened and metabolic pathways were better preserved. The age-linked opening was tied to H3K9 acetylation, which SIRT6 removes, but not to H3K56 acetylation. Delivering SIRT6 to the livers of already-old mice with an AAV vector partly restored youthful accessibility. The work suggests SIRT6 could be a target for reversing epigenetic aging, though it is so far limited to male mice.
