Researchers at Bar-Ilan University have discovered a potential way to reverse some of the molecular changes linked to aging by restoring youthful patterns of DNA organization in the livers of old mice. Published in the journal Nature Communications, the study highlights the important role of a protein called SIRT6, which appears to protect cells from age-related damage to chromatin. This tightly packed structure organizes DNA and controls gene activity. The findings suggest that aging may not simply result from irreversible wear and tear, but could instead involve biological changes that are at least partly reversible.
Inside every cell, DNA is folded into chromatin, a highly organized structure that helps determine which genes are active or silent. As organisms age, this structure can become disrupted, leading to abnormal gene activity and declining tissue function. Using advanced methods to examine DNA organization and gene expression, the researchers compared liver cells from young and old mice. They found that aging significantly altered chromatin architecture, activating inflammatory pathways while weakening genes responsible for healthy liver metabolism and normal cellular function.
Prof. Haim Cohen, Director of the Sagol Healthy Human Longevity Center at Bar-Ilan University’s Goodman Faculty of Life Sciences, said the genome gradually loses its proper organization over time. According to the researchers, genes that should normally remain inactive become switched on during aging, especially those linked to inflammation. At the same time, genes essential for maintaining healthy liver function become less active. These changes may contribute to the chronic inflammation and metabolic decline commonly associated with aging.
Remarkably, when researchers increased SIRT6 levels in already aged mice, many of these harmful chromatin changes were reversed. The team found that the old mice developed DNA organization patterns that more closely resembled those seen in younger animals. Prof. Cohen explained that SIRT6 appeared capable of “rewinding” aspects of the aging process by restoring healthier chromatin structure. The researchers also identified a chromatin marker known as H3K9ac that was strongly associated with age-related chromatin opening and inflammatory activation. SIRT6 helped restore a more youthful chromatin pattern at these specific sites.
The findings build on earlier research showing that SIRT6 plays an important role in promoting longevity and healthy aging. However, the new study goes further by suggesting that interventions targeting chromatin organization itself may help address one of the root biological mechanisms of aging. Rather than focusing on treating individual age-related diseases separately, scientists may eventually be able to target the underlying genomic instability that contributes to many forms of tissue decline. The work also supports the growing field of rejuvenation biology, which aims to reverse fundamental aspects of aging at the cellular level.
The study was led by PhD students Ron Nagar and Zacharia Schwartz from Bar-Ilan University’s Goodman Faculty of Life Sciences and the Sagol Healthy Human Longevity Center, together with collaborators from Tel Aviv University and the U.S. National Institute on Aging, including Prof. Rafael de Cabo and his research team. Although the findings are still limited to basic research in mice, the scientists believe the work opens an important new direction for understanding how aging develops and how it might one day be slowed, prevented, or partially reversed.
More information: Ron Nagar et al, SIRT6 overexpression counteracts chromatin aging in the male murine liver, Nature Communications. DOI: 10.1038/s41467-026-73115-y
Journal information: Nature Communications Provided by Bar-Ilan University
