Boosting Splicing Factor SRSF1 Reverses Molecular Signs of Aging in Mice
Researchers identified the splicing factor SRSF1 as a powerful regulator capable of shifting aged cells toward a more youthful gene expression profile without triggering full cellular reprogramming. Overexpression of SRSF1 in mice led to reduced molecular aging markers and extended healthy lifespan, offering a safer alternative to Yamanaka factors. This discovery highlights RNA splicing as a central control point for aging and opens new avenues for targeted anti-aging therapies.
In October 2026, researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University reported that overexpression of the splicing factor SRSF1 reversed molecular signs of aging in mice without inducing full cellular reprogramming. The study utilized a machine learning algorithm trained on transcriptomic data from human skin fibroblasts across a wide age range to predict "transcriptomic age." This predictive model enabled screening of genes capable of shifting aged cells toward a more youthful gene expression profile. SRSF1 emerged as the top candidate, reducing hallmarks of aging such as cellular senescence, proteostatic stress, and inflammaging in fibroblasts while preserving their identity—unlike Yamanaka factors, which trigger pluripotency and cancer risk. When delivered to aged mice, SRSF1 accumulated primarily in the liver and extended healthy lifespan by 14%, marking it as a potential geroprotective target. The findings highlight RNA splicing as a central regulatory node in aging, offering a safer alternative to full reprogramming.
This work builds on growing concern over the oncogenic risks of Yamanaka factors—key tools in cellular reprogramming that can lead to tumor formation due to loss of cell identity and uncontrolled proliferation. Researchers have long sought ways to achieve rejuvenation without dedifferentiation, particularly for therapeutic applications across diverse tissues. The team’s approach leveraged high-throughput screening
This discovery could significantly influence the development of anti-aging therapies by offering a potentially safer route to cellular rejuvenation than Yamanaka factor-based reprogramming. If SRSF1 proves effective in humans, it may lead to new treatments for age-related diseases such as fibrosis, metabolic disorders, and organ decline—particularly those linked to chronic inflammation or protein misfolding. The pharmaceutical and biotech sectors may accelerate investment in splicing factor modulation, with companies specializing in RNA therapeutics likely to expand into longevity applications. A comparable precedent is the development of senolytics, which selectively clear senescent cells; like SRSF1, they aim to target aging mechanisms without altering cell identity. However, unlike senolytics, SRSF1 acts upstream by reshaping gene expression networks, potentially offering broader effects. The next steps will involve testing in primates and assessing long-term safety, especially rega