SRSF1 Gene Delivery Extends Lifespan in Aged Mice

An RNA sequencing and machine learning screening platform identified an RNA-processing factor that reduced markers of cellular aging without erasing cell identity

October 19, 2026
3 min

The Medicine Maker

Overview

A Nature Aging study identified SRSF1, an RNA-splicing regulator, through a transcriptomic screen and reported reduced aging-associated cellular features in human fibroblasts. In aged female mice, inducible SRSF1 delivery was associated with a 14% increase in median lifespan, slower frailty accumulation, and delayed sustained frailty; the findings are preclinical and based on a small cohort.

Background

Partial cellular reprogramming can reverse some molecular features of aging, but excessive expression of Yamanaka factors can cause mature cells to lose their identity and may increase tumor risk. The study sought factors that shift aged cells toward younger states while preserving specialized cell characteristics. SRSF1 encodes a splicing factor involved in determining which RNA sequences are retained in mature messenger RNA. The researchers are investigating how its effects on RNA processing produce the observed cellular and organism-level outcomes.

Data Highlights

Measure	Finding
Human fibroblast screening dataset	464 samples from donors of different ages
Median lifespan in aged female mice	778 days in controls; 886 days with inducible SRSF1 delivery
Median lifespan difference	14% increase reported with treatment
Frailty accumulation	Rate reduced by approximately 44%
Onset of sustained frailty	Delayed by 123 days
Mouse cohort size	n=9–10 per group, as reported in the web research context

Key Findings

A machine-learning model trained on gene-expression data from 464 human fibroblast samples assessed age-associated changes across multiple cellular processes.
Among screened candidates, SRSF1 overexpression produced the most consistent reduction in predicted transcriptomic age.
In human fibroblasts, SRSF1 was associated with reduced cellular senescence, inflammatory signaling, and proteostatic stress, alongside restored DNA-repair programs; treated cells retained fibroblast morphology and function-associated gene expression.
Inducible SRSF1 delivery using an adeno-associated viral vector primarily targeting the liver increased median lifespan in aged female mice from 778 to 886 days and delayed sustained frailty by 123 days.
The rate of frailty accumulation was approximately 44% lower in treated mice; the reported survival cohort was small (n=9–10 per group).
Constitutive overexpression produced higher SRSF1 levels but did not improve skin repair or muscle regeneration, indicating that the reported effects depended on controlling expression timing and level.

Clinical Implications

The findings are preclinical and do not establish efficacy or safety in humans. The study's authors report that SRSF1 expression level and timing mattered, while the web research context notes that future geroscience trials should pair biological-age measures with clinically meaningful functional outcomes.

Conclusion

Controlled SRSF1 delivery was associated with lifespan and frailty-related effects in aged mice and with younger cellular features in human fibroblasts. Further work is needed to clarify the RNA-processing mechanisms and assess whether the findings translate beyond this preclinical setting.