Many MindedA splicing protein, SRSF1, turns back cellular age and stretches mouse life
Researchers have identified SRSF1, an RNA-processing and splicing factor, as a molecule that can push cells toward a younger state. Its expression falls as human fibroblasts age. The work is preclinical, so any therapy is a long way off.
The team first trained a machine-learning age predictor on gene expression from dermal fibroblasts donated by people aged 1 to 96. It picked up the effects of interventions faster than a widely used DNA methylation clock. They then overexpressed a library of genes tied to human aging networks and scored each one. SRSF1 was the most robust hit, comparable to the Yamanaka factors (OSKM). In cell culture it lowered senescence markers, inflammatory signaling and proteostatic stress, and boosted DNA repair. Unlike OSKM, it lowered transcriptomic and epigenetic age without the cells losing their identity in transcriptional state or morphology.
In aged mice, acute SRSF1 induction cut frailty by 44%, sped wound closure, lowered mortality risk and extended median lifespan by 14%. The viral vector targeted the liver, and treated livers showed reduced stress, inflammatory and cell-cycle pathways, similar to the human cells.
Why it matters: age-related disease drives much of the cost of health care. A target that resets cell state without erasing cell identity addresses a known risk of full reprogramming and could widen the route to cheaper, broader treatments.
The caveats are large. Groups were 9–10 female mice each. Constitutive induction gave higher SRSF1 levels without toxicity but did not improve wound repair or muscle regeneration, so timing and dose matter. First co-author Alex Plesa thinks liver targeting very likely benefits other organs, but that is speculation, not a result. The link between lower frailty and longer life is an association. Watch for replication, male animals, and other tissues.
Source: Lifespan.io