Researchers Discover Transcription Factors That Can Reverse Aging in Mice

Manipulating gene activity through key transcription factors may hold promise for reversing some effects of aging.

Published on Feb. 24, 2026

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Researchers at the University of California, San Francisco have identified several transcription factors that, when their levels are altered, can reverse age-related changes in gene expression and improve markers of health in aged mice. By boosting levels of transcription factors like EZH2 and E2F3, or reducing levels of STAT3 and ZFX, the scientists were able to make old mouse cells behave more like younger cells. This approach holds potential for developing interventions to address the health consequences of aging, though significant further study will be needed before it could be used in humans.

Why it matters

As people age, changes in gene expression contribute to the development of age-related diseases and health problems. Identifying ways to reverse these age-related changes in gene activity could lead to new therapies to help people stay healthier for longer. This research provides an important step forward in understanding how manipulating key transcription factors may be a viable approach for reversing some of the negative effects of aging.

The details

The research team developed a system to screen hundreds of transcription factors, identifying four key ones - EZH2, E2F3, STAT3, and ZFX - that when altered, were able to reverse age-related changes in gene expression in human cells and improve markers of health in aged mice. Increasing EZH2 and E2F3 levels, or decreasing STAT3 and ZFX levels, led to improved cell function, reduced fat buildup and scarring, and better glucose tolerance in older mice, without causing liver damage or changes linked to cancer.

  • The research findings were published on January 9, 2026 in the Proceedings of the National Academy of Sciences.
  • The research was conducted by a team at the University of California, San Francisco, led in part by Drs. Changhui Deng, Saul A. Villeda, and Hao Li.

The players

University of California, San Francisco

The research was conducted by a team at the University of California, San Francisco.

Changhui Deng

One of the lead researchers on the study from the University of California, San Francisco.

Saul A. Villeda

One of the lead researchers on the study from the University of California, San Francisco.

Hao Li

One of the lead researchers on the study from the University of California, San Francisco.

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What they’re saying

“By altering gene expression using the transcription factors we identified, old fibroblasts behaved as if they were younger, and improved the health of old mice.”

— Hao Li (Proceedings of the National Academy of Sciences)

What’s next

The researchers note that considerable further study will be needed before this approach could be used in people, as manipulating transcription factors can have unintended effects due to their influence on many target genes.

The takeaway

This research provides an important step forward in understanding how targeting key transcription factors may hold promise for developing interventions to reverse some of the negative health effects of aging, though significant additional work is still required before this could be applied clinically.