SRSF1 Gene Identified as Geroprotective Target to Reverse Cellular Aging
Scientists have isolated a single RNA processing factor that reduces biological markers of aging and extends the lifespan of mice by 14 percent without disrupting specialized cell identity.
Aging progressively degrades cellular function across every human tissue, driving conditions that account for the vast majority of age-related mortality. While Shinya Yamanaka demonstrated in 2006 that overexpressing four specific genes can revert mature cells to an undifferentiated pluripotent state, that process risks losing cellular identity and triggering uncontrolled growth. Researchers have instead sought specific genetic levers that turn back the biological clock safely.
Transcriptomic Machine Learning Predicts Biological Age in Skin Cells
To identify safer rejuvenation candidates, a research team led by George Church at the Wyss Institute at Harvard University and spearheaded by Wyss Institute Scientist Alex Plesa collaborated with Antonio del Sol’s computational biology group at CIC bioGUNE-BRTA in Spain. The investigators designed a machine learning algorithm trained on transcriptomic profiles across multiple aging processes in human skin fibroblast cells. The model evaluates gene expression changes much like odometers track different parts of a vehicle, providing a scorable readout of biological age.
Using this predictor, the team screened a focused library of candidate genes to find interventions that could shift the transcriptomic age of old cell lines toward a youthful state. The top-scoring candidate was a gene encoding the RNA processing factor SRSF1. When overexpressed in human fibroblasts, SRSF1 mitigated cellular senescence, reduced chronic low-grade inflammation known as inflammaging, and relieved proteostatic stress while restoring DNA repair mechanisms.
Liver-Tropic Gene Therapy Extends Mammalian Lifespan
To test whether these cellular effects translate to living animals, the researchers packaged the SRSF1 gene into a liver-tropic adeno-associated virus and administered it to aged mice. The treatment successfully concentrated in the liver, slowed the rate of physical frailty, and extended the median lifespan of the treated animals by 14 percent compared to control groups.
SRS1 functions primarily as an RNA splicing factor that helps include alternative exon sequences in messenger RNA molecules, altering the resulting proteins. Plesa noted that while the team observed a strong trend of alternatively spliced mRNAs, investigators are still mapping how those molecular adjustments generate widespread tissue rejuvenation. The findings were published in Nature Aging.
Frequently Asked Questions About SRSF1 and Cellular Rejuvenation
How does SRSF1 differ from Yamanaka factors in cellular reprogramming?
While Yamanaka factors force mature cells back into an undifferentiated, pluripotent state, SRSF1 rejuvenates cells without erasing their specialized identity. Fibroblasts treated with SRSF1 maintained their normal spindle-shaped morphology and continued expressing typical functional genes rather than activating pluripotency programs.
Which research institutions contributed to the SRSF1 aging study?
The research was led by the Wyss Institute at Harvard University in collaboration with the computational biology group at CIC bioGUNE-BRTA, the Basque Research and Technology Alliance in Spain. Additional funding and support came from the Aging and Longevity-Related Research Fund, the Astera Fund at the Silicon Valley Community Foundation, and the Spanish Ministry of Science and Innovation.
What specific hallmarks of aging does SRSF1 target?
SRSF1 addresses multiple aging drivers simultaneously, including cellular senescence where damaged cells stop dividing, proteostatic stress involving protein turnover imbalances, and chronic inflammatory signaling.
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