Can an Aging Liver Recall How to Be Young?

Every cell in the body carries the same genetic “book.” Yet a liver cell knows how to behave like a liver cell, a heart cell knows how to beat, and a brain cell knows how to think, signal, and remember. The difference lies not in the book itself, but in the way each cell reads it.

With age, that reading process begins to falter.

In a new study published in Nature Communications, researchers at Bar-Ilan University show that some of the deep cellular changes associated with aging may be more flexible than once thought. By increasing the activity of a protein called SIRT6, previously linked to longevity and healthy aging, the researchers were able to restore key patterns in the aging livers of mice to a state resembling that of young mice.

The study was led by Prof. Haim Cohen of Bar-Ilan University’s Mina and Everard Goodman Faculty of Life Sciences and the Sagol Healthy Human Longevity Center, together with doctoral students Ron Nagar and Zacharia Schwartz, who contributed equally to the research.

The “instruction manual” inside the cell

To understand the discovery, it helps to imagine DNA as an enormous instruction manual. The challenge for the cell is not only to preserve the manual, but also to know which pages should be open, which should be closed, and when each instruction should be read.

This is the role of chromatin, the structure that packages DNA inside the cell nucleus. Chromatin is not merely storage. It helps determine which genes are available for use and which remain silent. In a young, healthy liver cell, this system is carefully organized. The right genetic programs are accessible, and the cell can maintain its identity and function.

But with age, the researchers found, this organization begins to break down. Regions of chromatin that were once closed may open, while regions that were once active may close. The result is a disruption in the liver cell’s internal operating system: genes connected to normal liver function can lose their rhythm, while pathways associated with inflammation and decline may become more active.

Where SIRT6 enters the story

SIRT6 is a protein that operates inside the cell nucleus and is involved in several essential processes, including DNA repair, gene regulation, metabolism, and the response to cellular stress. Over the past decade, it has become one of the most intriguing proteins in aging research.

Prof. Cohen and his team have been studying SIRT6 for years. In previous work, they showed that increasing SIRT6 expression in mice extended lifespan and improved multiple health-related measures, including metabolic function, blood biochemistry, and the ability to use energy stores more efficiently in old age.

The new study asked a deeper question: could SIRT6 affect one of the basic mechanisms of cellular aging itself, the way DNA is packaged, opened, and read?

The answer, in mice, was striking.

Restoring order in an aging liver

The researchers first examined mice genetically engineered to express higher levels of SIRT6 from a young age. In these mice, many of the age-related disruptions in chromatin structure were prevented, allowing older liver cells to retain patterns that looked much more like those of younger animals.

But the more important question was whether SIRT6 could help after aging had already begun.

That question matters because any future therapy for humans would not begin at birth. It would need to work in older people, after age-related changes have already taken place.

To test this, the researchers allowed mice to age naturally. Then, at 24 months old, roughly comparable to 70–80 years of age in humans, they increased SIRT6 activity specifically in the liver. Within one month, a major portion of the age-related chromatin changes shifted back toward a youthful pattern.

The effect was not limited to the structure of DNA packaging. The researchers also observed reduced inflammation and improved metabolic pathways, suggesting that the liver was not only “looking” younger at the molecular level, but also regaining aspects of younger function.

A promising direction, not a treatment yet

The findings point to an exciting possibility: some age-related changes in tissues may not be entirely one-way. At least in the mouse liver, SIRT6 appears capable of restoring part of the cellular order that is gradually lost with age.

At the same time, the researchers emphasize that this is still early-stage science. There is currently no approved treatment in humans that performs this kind of intervention. More research is needed before the findings can be translated into clinical use.

Still, the study offers a powerful new direction for the field of healthy aging. Rather than focusing only on extending lifespan, the work points toward a more meaningful goal: improving the physiology and function of older tissues, so that added years can also be healthier years.

For Prof. Cohen, this is the heart of the research. The goal is not simply to make organisms live longer, but to understand how aging works at its most basic level and how science may one day help the aging body function better.