Israeli Study Finds Key Protein That Reverses Cellular Ageing in Mice

Israeli study points to potential reversal of cellular ageing

Tel Aviv, May 30

The study showed that increasing the activity of a protein called SIRT6 can reverse age-related deterioration in how DNA is organised and used inside cells. Researchers say this is the first time SIRT6 has been shown to restore youthful molecular patterns in already aged animals, rather than merely slowing age-related changes when activated earlier in life.

"We essentially took the liver and rejuvenated it," research leader Prof. Haim Cohen told The Press Service of Israel. "We restored it to being a young liver at the most fundamental level -- like an instruction book that is clear and properly organised again."

The study, authored by doctoral students Ron Nagar and Zacharia Schwartz, was published in the peer-reviewed journal Nature Communications.

To explain the significance of the findings, the researchers describe DNA inside cells as an instruction manual for the body. DNA is tightly packaged and organised by a structure called chromatin, which determines which genes are accessible and active and which remain switched off. In young, healthy cells, this system is carefully controlled so that the right genes are active at the right time.

However, with age, this organisation becomes less stable.

"Imagine a book that becomes wrinkled and hard to read, and the structure is no longer organised properly," Cohen told TPS-IL. "What happens with age is that the DNA system loses its order. Genes that should be active do not work, and genes that should be silent become active."

SIRT6 is a protein inside cells that helps regulate DNA repair, gene activity, metabolism, and the way cells respond to stress. It has been studied for years because of its association with healthy ageing and longevity. Earlier research showed that higher levels of SIRT6 in mice were linked to longer life and improved metabolic health. However, it remained unclear whether the protein could actually reverse ageing changes once they had already occurred.

The team tested this question directly in mice that were already old, at about 24 months of age, which is roughly comparable to humans in their 70s or 80s. After increasing SIRT6 activity specifically in the liver, the researchers found that within about a month, the structure of chromatin in liver cells shifted back toward patterns typically seen in young animals.

The mice also showed reduced inflammation and improved metabolic function, suggesting that the liver was not only appearing younger at the molecular level but also functioning more efficiently.

"This means that if we apply this approach in humans, we may be able to bring the liver back to a healthier and more youthful state in old age," Cohen told TPS-IL.

The researchers reported that they did not observe harmful side effects in mice with increased SIRT6 activity. "In fact, we saw better health overall. Their metabolism, activity levels, and even tumour rates were more similar to young mice," Cohen said.

The effects also appeared to last. Cohen said the youthful state of the liver remained for at least three months after treatment in older mice, which could be roughly comparable to several years in human terms.

The findings raise the possibility that future treatments might target ageing itself, rather than only treating diseases that come with age. One possible application mentioned by Cohen is improving recovery and resilience in older patients, such as after surgery or illness, when the body often struggles to return to normal function.

An Israeli company, SirTLab, is already developing therapies based on SIRT6 activation. The company is working on compounds designed for potential use in humans and is currently seeking funding to advance toward clinical trials.

"The main challenge is funding, as always," Cohen told TPS-IL.

Despite the encouraging results, researchers caution that many questions remain, including how SIRT6 restores youthful DNA organisation and whether similar effects can be safely achieved in other organs beyond the liver. Still, Cohen said the findings suggest that some aspects of ageing may be more biologically flexible at the cellular level than previously believed. "Right now it looks very promising," he told TPS-IL.

— ANI