SIRT6 reverses aging

Researchers at Bar-Ilan University have successfully restored DNA organization patterns in the livers of aged mice, reversing key molecular features associated with aging. The study, published in Nature Communications., identifies the protein SIRT6 as a potent protector against age-related breakdown of chromatin, the complex system that packages DNA and controls how genes are turned on and off.

The findings suggest that aging is not simply a passive process of wear and tear, but may also be due in part to reversible changes in the way DNA is organized within cells.

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DNA inside cells is tightly “folded” and “packaged” into chromatin, a structure that acts as a biological control system for gene activity. Using advanced tools to study DNA organization and gene activity, the researchers examined a wide range of molecular changes in the livers of young and old mice. What they discovered was startling: aging disrupts the chromatin architecture in the liver, triggering overactive inflammatory pathways while also weakening the metabolic programs that define healthy liver tissue.

“As we age, the genome loses its proper organization,” said Professor Haim Cohen, Director of the Sagol Center for Healthy Human Longevity at Bar-Ilan University’s Goodman School of Life Sciences, who led the study. “Genes that should remain inactive become activated, especially inflammatory genes, while genes required for normal liver function begin to be deactivated.”

Remarkably, when the scientists increased SIRT6 levels in already aged mice, many of these age-related chromatin changes were reversed.

"What we found is that SIRT6 can help to reverse this process. Simply put, we took an old liver and restored its DNA organization to a much younger state," said Professor Cohen.

The study adds an important new layer to previous discoveries showing that SIRT6 promotes longevity and healthy aging. Rather than focusing on individual diseases, the new findings suggest the possibility of targeting one of the core biological mechanisms of aging itself: the loss of proper genome regulation.

“This is exciting because it suggests that aging may be more resilient than we once thought,” said Professor Cohen. “If we can restore healthy chromatin organization, we may ultimately be able to preserve tissue function, reduce inflammation and improve health as we age.”

The research was conducted by doctoral students Ron Nagar and Zacharia Schwartz, from the Mina and Everard Goodman School of Life Sciences and the Sagol Center for Healthy Human Longevity at Bar-Ilan University, along with collaborators from Tel Aviv University and the National Institute on Aging, including Professor Rafael de Cabo and his team.

 

DOI https://doi.org/10.1038/s41467-026-73115-y


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