San Francisco, January 26, 2026 – As we get older, bouncing back from illness or injury just isn’t what it used to be. But a new study from researchers at UCSF reveals that specific proteins-gene regulators that switch genes on and off-could potentially restore the body’s youthful ability to heal itself. Could we one day rewind the clock on tissue repair?
Restoring the body’s Repair Mechanisms
Scientists have identified gene regulators that may reverse age-related decline in tissue repair.
- the research focused on fibroblasts, cells crucial for building and maintaining organ structure.
- A computational analysis pinpointed transcription factors that could reverse age-related gene expression changes.
- Adjusting levels of these factors rejuvenated cells in lab dishes and improved liver health in aging mice.
- The findings offer promising avenues for treating age-related diseases.
The team investigated fibroblasts, the workhorse cells responsible for constructing the scaffolding of organs and tissues. As we age,these cells lose their efficiency,contributing to slower healing and increased susceptibility to disease. The study, published January 9 in Proceedings of the National Academy of Sciences, received funding from the National Institutes of Health.
Dr.Li’s team began by comparing gene expression patterns in young and old fibroblasts as they grew in petri dishes. Using computational modeling,they identified the transcription factors driving this aging process.
Next, they employed CRISPR technology to prompt these transcription factors to give old fibroblasts a younger gene expression profile. The results were striking: adjusting the levels of any one of 30 transcription factors triggered “young” gene expression in the aged cells. Further refinement revealed that changes to the levels of just four of these factors boosted metabolism and enhanced the ability of the old fibroblasts to multiply.
“Our work opens up exciting new opportunities to understand and ultimately reverse aging-related diseases,” said Janine sengstack, PhD, who led the project as a graduate student in Dr. Li’s lab and is the first author of the paper.
Could this research lead to treatments for age-related diseases? The identification of these key transcription factors offers a potential pathway for developing therapies that target the basic mechanisms of aging.
Reference: Sengstack J,Zheng J,Aghayev T,et al. Systematic identification of single transcription factor perturbations that drive cellular and tissue rejuvenation. Proc Natl Acad sci USA. 2026;123(2):e2515183123. doi: 10.1073/pnas.2515183123
