Reversing Liver Aging: Study Shows SIRT6 Protein Restores Youthful DNA Organization in Mice

A study published in Nature Communications by researchers from Bar-Ilan University in Israel and collaborators in the United States has found that increasing levels of the SIRT6 protein can reverse age-related deterioration in DNA organization and gene expression in the livers of aged mice.

Key Findings

Researchers increased SIRT6 levels in two-year-old mice, an age equivalent to approximately 70–80 years in humans. After one month, the chromatin patterns in the mice's livers reverted to a youthful state, reversing approximately 80% of age-related changes.

"We essentially took the liver and rejuvenated it. We restored it to being a young liver at the most fundamental level." — Prof. Haim Cohen, lead researcher

Chromatin is the system that packages DNA and controls gene activity. Aging disrupts this organization, leading to the activation of inflammatory genes and the weakening of genes essential for healthy liver function. The study demonstrated that after increased SIRT6 activity, the chromatin structure in liver cells shifted to patterns typical of young animals.

Treated mice also showed reduced inflammation and improved metabolic function. The researchers reported that the youthful state persisted for at least three months after treatment.

Genetically engineered male mice with higher SIRT6 levels maintained a youthful, densely packed chromatin structure into old age. Increasing SIRT6 levels in already elderly mice reversed many age-related chromatin changes within one month, shifting them toward a more youthful state.

Background

SIRT6 is a protein involved in DNA repair, gene activity regulation, metabolism, and stress response. Previous studies on centenarians linked SIRT6 to longer life, revealing a more active variant of the protein in those individuals. Earlier research has also linked higher SIRT6 levels to longer lifespan and better metabolic health in mice.

This study is the first to show that SIRT6 can restore youthful molecular patterns in already aged animals.

Research Statements

Prof. Haim Cohen characterized age-related loss of DNA organization with a vivid analogy:

"Imagine a book that becomes wrinkled and hard to read, and the structure is no longer organized properly."

Regarding the animals' overall health, Cohen stated:

"We saw better health overall. Their metabolism, activity levels, and even tumor rates were more similar to young mice."

Potential Applications & Cautions

The researchers noted that the results are not directly transferable to humans due to ethical and practical limitations of genetic modification. The findings provide a basis for further research into aging mechanisms and potential interventions.

Cohen suggested that future therapies could target aging itself, potentially improving recovery and resilience in older patients after surgery or illness. SirTLab, an Israeli company, is developing SIRT6-based therapies for human use and seeking funding for clinical trials.

Researchers cautioned that many questions remain, including the precise mechanism of action and whether similar effects can be achieved safely in other organs.