Researchers trained a machine-learning model on fibroblast gene expression from donors aged 1 to 96 to score cellular age, then screened candidate genes for reversal of that signature. SRSF1, an RNA-processing and splicing factor that declines with fibroblast aging, emerged as the strongest hit, rejuvenating human cells without erasing cell identity and, when induced in aged mice via a liver-tropic vector, reducing frailty by 44% and extending median lifespan by 14%.
Key Points
- SRSF1 induction extended median lifespan 14% in aged mice
- Frailty fell 44%; wound closure accelerated, mortality risk declined
- Rejuvenation occurred without loss of cell identity, unlike Yamanaka reprogramming
Longevity Analysis
Transcriptomic age scoring reacts faster and at lower cost than methylation clocks, making it a practical readout for screening interventions rather than merely cataloguing damage — a measurement advance as consequential as the molecule itself. SRSF1 acts on the upstream machinery that determines which proteins a cell builds, and its induction lowered senescent signaling and inflammatory output while restoring DNA repair capacity, linking repair capability to whole-animal frailty and wound healing. That the effect emerged from a vector concentrated in the liver points to detoxification and metabolic tissue as a systemic lever, with benefits propagating well beyond the targeted organ.
Original published by LifeSpan.io, by Anna Drangowska-Way.