One Gene, a 14% Longer Mouse Lifespan, and a New Rejuvenation Lead

Key Takeaways

• Researchers built a machine-learning model that estimates the biological state of cells from their gene-expression patterns, then used it to screen candidate genes for rejuvenation effects.

• One gene, SRSF1, reduced several aging-related features in older human skin cells, including senescence-associated signals, protein-maintenance stress, and inflammatory signaling.

• The cells retained their specialized fibroblast identity, an important distinction from broader reprogramming approaches that can push cells toward an immature state.

• In older mice, a virus designed to deliver SRSF1 primarily to the liver slowed the development of frailty and increased median lifespan by 14% compared with control mice.

• The work does not establish safety, an effective dose, durability, or benefit in people; gene delivery itself remains a major translational hurdle.

Looking Beyond Full Reprogramming

Scientists have long explored whether aging cells can be pushed toward a younger biological state. One well-known approach uses a group of genes that can broadly reset cell identity—but that breadth creates risk, including the possibility of driving cells too far from their normal roles.

This team took a narrower route: search for a single gene that improves aging-related processes while allowing cells to remain recognizably themselves. SRSF1 emerged as the strongest candidate from that screen.

A Different Kind of Aging Clock

Rather than relying only on chemical tags on DNA, the researchers used patterns of gene activity to estimate a cell’s “transcriptomic age.” Their model was trained on 464 human skin-cell samples from donors spanning a wide age range.

That model gave researchers a scalable way to look for interventions that move multiple aging-related gene networks in a younger-looking direction. In cultured older cells, increasing SRSF1 shifted several molecular and functional signals while preserving normal fibroblast characteristics.

From Cells to Mice

The researchers then packaged SRSF1 in an adeno-associated virus designed to concentrate in the liver of older mice. Treated animals developed frailty more slowly and lived longer on average than controls.

The finding is especially notable because the intervention appeared to act through an existing RNA-processing system, rather than forcing cells into a radically different identity. But scientists do not yet know how the liver-focused intervention produced wider effects across the body—or whether that pattern would translate to people.

A Promising Signal, Not a Therapy

This is among the more interesting recent demonstrations that targeted gene regulation can influence multiple hallmarks of aging at once. Yet the gap between a successful mouse gene-delivery experiment and a safe human intervention is large.

Before any clinical relevance is clear, researchers will need to test long-term safety, dose control, tissue targeting, unintended effects, and whether the benefits persist. For now, SRSF1 is best viewed as a compelling new target—and a reminder that aging biology may be modifiable without completely rewriting what a cell is.

References:

Plesa, A.M., Jung, S., Wang, H.H. et al. Transcriptomic reprogramming screen identifies SRSF1 as a regulator of aging. Nat Aging 6, 2057–2073 (2026). https://doi.org/10.1038/s43587-026-01234-8