Scientists at Bar-Ilan University have shown that aspects of liver aging in mice can be partially reversed by increasing levels of the protein SIRT6. As mice age, the packaging of DNA in liver cells—known as chromatin—becomes disorganized, leading to increased inflammation and reduced metabolic function. By boosting SIRT6, researchers were able to restore chromatin structure toward a more youthful state, even when treatment began late in life. The study, published in Nature Communications, used genetically modified mice and viral vectors to elevate SIRT6 in hepatocytes, resulting in reversal of about 80 percent of age-related chromatin changes.

The team analyzed liver tissue from young (5–7 months) and old (18–21 months) male mice using ATAC-seq and RNA-seq, finding that aging loosened chromatin overall, especially at regions linked to inflammation. In mice with elevated SIRT6, these changes were largely prevented. The protein appeared to maintain youthful gene expression patterns by preserving the balance between inflammatory genes and those essential for liver metabolism. Notably, SIRT6's effect was linked to regulation of the histone mark H3K9ac, which increased at key sites in aging livers but remained stable in treated mice.

While the findings are promising, they are limited to male mice and do not yet prove life extension or disease prevention in humans. The research supports the theory that aging involves loss of epigenetic control rather than just accumulated damage, opening new paths for therapies targeting root mechanisms. However, translating these results to humans will require further study of SIRT6's role across tissues and sexes, as well as development of safe delivery methods.