An old liver's DNA organization shifted back toward a younger state
In the liver cells of aging mice, scientists at Bar-Ilan University have demonstrated something quietly profound: that the molecular disorder we call aging is not entirely a one-way passage. By elevating a single protein, SIRT6, researchers restored the youthful organization of DNA packaging in old tissue, silencing inflammatory genes that had grown too loud and reawakening the quieter signals of healthy function. The finding, published in Nature Communications, invites a reconsideration of aging itself—not as an irreversible unraveling, but as a process with latent capacity for renewal.
- Aging scrambles the architecture of DNA inside cells, activating inflammatory genes that should stay silent while shutting down the very pathways that keep liver tissue healthy—a molecular disorder once assumed to be permanent.
- Researchers identified a specific chromatin marker, H3K9ac, as a key site where this age-related chaos takes hold, giving them a precise molecular target to work against.
- When SIRT6 protein levels were boosted in already-old mice, the chromatin patterns began shifting back toward a younger state—suggesting the damage is not fixed but responsive to intervention.
- The study reframes the ambition of aging research: rather than fighting individual diseases one by one, restoring genome regulation could address aging's underlying machinery all at once.
- The critical open question now is whether this molecular reversal can cross from mouse biology into human medicine, and whether SIRT6-targeting therapies might one day be a practical tool against aging itself.
Inside the liver cells of aging mice, researchers at Bar-Ilan University uncovered something that challenges a foundational assumption about growing old. By boosting levels of a protein called SIRT6, they were able to restore the youthful organization of chromatin—the packaging system that governs which genes are active and which remain silent—in livers that had already aged. The work, published in Nature Communications, suggests that aging carries within it at least some reversible components.
As cells age, the physical organization of DNA does not simply wear down passively. It becomes disordered in specific, consequential ways: genes that should stay quiet, particularly those driving inflammation, get switched on, while the genes responsible for normal liver function begin to go dark. Using advanced genomic mapping tools, the team compared young and old mouse livers and found the contrast stark—aging had effectively scrambled the chromatin architecture.
Haim Cohen, who led the study at Bar-Ilan's Sagol Healthy Human Longevity Center, framed the central question plainly: could this process be reversed? When SIRT6 levels were increased in already-old mice, the answer was yes. The researchers also identified a specific chromatin marker, H3K9ac, closely tied to age-related gene activation, and found that SIRT6 helped restore a younger pattern at these sites—essentially rewinding one of aging's molecular clocks.
The broader implication is philosophical as much as scientific. If chromatin organization can be therapeutically restored, it may become possible to target aging itself rather than its downstream diseases. The next frontier is translation: whether what holds in mouse livers can eventually apply to human biology, and whether SIRT6-targeting treatments might one day slow aging's molecular progression in people.
Inside the liver cells of aging mice, something unexpected happened. Researchers at Bar-Ilan University found they could turn back the clock on one of aging's most fundamental processes: the way DNA gets organized and controlled inside cells. By boosting levels of a protein called SIRT6, they restored the youthful architecture of chromatin—the intricate packaging system that determines which genes stay silent and which ones switch on—in livers that had grown old. The work, published in Nature Communications, suggests that aging is not simply a one-way slide into decay, but rather a process with reversible components, at least at the molecular level.
The discovery challenges a long-held assumption about how aging works. As we grow older, the genome doesn't just wear out passively. Instead, the physical organization of DNA inside cells becomes chaotic. Genes that should remain quiet get activated, particularly those that trigger inflammation. Meanwhile, the genes responsible for keeping liver tissue healthy and metabolically functional begin to shut down. Using advanced tools to map DNA organization and track which genes were active, the researchers compared young and old mouse livers side by side. The difference was stark: aging had scrambled the chromatin architecture, turning up the volume on inflammatory pathways while dimming the signals that maintain normal liver function.
Haim Cohen, who directed the study at Bar-Ilan's Sagol Healthy Human Longevity Center, described the finding in straightforward terms: as we age, the genome loses its organizational structure. Genes that should stay silent become activated, especially inflammatory ones, while genes needed for normal liver function shut down. The question was whether this process could be reversed. When the team increased SIRT6 levels in already-old mice, the answer came back yes. The age-related chromatin changes began to reverse. An old liver's DNA organization shifted back toward a younger state.
The researchers pinpointed a specific chromatin marker called H3K9ac that appears closely tied to age-related chromatin opening and the activation of inflammatory responses. SIRT6 helped restore a younger chromatin pattern at these sites, essentially rewinding one of aging's molecular clocks. This builds on earlier work showing that SIRT6 promotes longevity and supports healthy aging, but this study goes deeper—it suggests that rather than treating individual age-related diseases one at a time, there may be a way to target aging itself by restoring proper genome regulation.
Cohen emphasized the philosophical shift this represents. Aging may be more plastic, more malleable, than previously believed. If researchers can restore healthy chromatin organization in cells, the possibility emerges of preserving tissue function, reducing inflammation, and improving overall health during the aging process. The work involved Ph.D. students Ron Nagar and Zacharia Schwartz from Bar-Ilan, along with collaborators from Tel Aviv University and the National Institute on Aging, including Rafael de Cabo and his team. The next question is whether what works in mouse livers can eventually translate to human biology—and whether SIRT6-targeting treatments might one day slow aging's molecular progression in people.
Notable Quotes
As we age, the genome loses its proper organization. Genes that should remain silent become activated, especially inflammatory genes, while genes required for normal liver function begin to shut down.— Prof. Haim Cohen, Bar-Ilan University
We took an old liver and restored its DNA organization to a much younger state.— Prof. Haim Cohen
The Hearth Conversation Another angle on the story
So they made old mice younger at the cellular level? That sounds almost too clean.
Not younger overall—just their liver cells' DNA organization. The chromatin architecture reverted to a younger pattern. It's a specific molecular reversal, not a fountain of youth.
But why does DNA organization matter so much? Why not just fix the diseases that come with age?
Because the disorganization is upstream of the diseases. When chromatin gets chaotic, inflammatory genes turn on and metabolic genes turn off. That's the root problem. Fix the organization, and you're addressing the cause, not just the symptom.
And SIRT6 is the key to fixing it?
In these mice, yes. When they boosted SIRT6, the chromatin pattern shifted back toward youth. It's not a cure—it's a proof that the process isn't irreversible, which changes how we think about aging.
What's the catch? Why isn't this already in human trials?
Mouse livers are one thing. Human biology is vastly more complex. And we don't yet know if boosting SIRT6 in people would be safe or effective. But the principle—that aging's molecular changes can be reversed—that's the real finding.