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    PAPER SRSF1-Preclinical Study2026

    Transcriptomic reprogramming screen identifies SRSF1 as a regulator of aging

    Non-pluripotency-based gene rejuvenation: SRSF1 reportedly reverses transcriptomic and cellular aging hallmarks in fibroblasts while preserving cell identity, and AAV-SRSF1 reportedly extended median lifespan by about 14% in aged mice. Lifespan figure is taken from institutional press coverage; sample sizes and survival curves were not verified.

    Evidence

    4/10

    Emerging Evidence

    Sample

    —

    subjects

    Duration

    —

    study period

    Journal

    Nature Aging

    Oct 2026

    Authors

    Authorship

    Plesa AM, Jung S, Church GM, del Sol A, Wagers AJ, Mair WB

    01

    Full Abstract

    A machine-learning transcriptomic-age predictor trained on human skin fibroblasts was used to screen a library of age-related genes in aged fibroblasts; the RNA splicing factor SRSF1 ranked highest as a rejuvenating factor. Liver-tropic AAV delivery of SRSF1 to aged mice is reported to extend median lifespan.

    02

    Key Findings

    1. 01

      Transcriptomic-age screen ranked SRSF1 (RNA splicing factor) as top rejuvenation candidate in aged human fibroblasts

    2. 02

      Rejuvenated fibroblasts reportedly kept fibroblast identity and did not activate pluripotency programs

    3. 03

      Reduced senescence, inflammatory signaling and proteostatic stress; restored DNA-repair programs (reported)

    4. 04

      Liver-tropic AAV-SRSF1 reportedly extended median lifespan ~14% in aged mice and slowed frailty (press coverage; n not verified)

    03

    Structured Methods

    Study Design
    Preclinical Study
    Sample Size
    Not reported
    Study Duration
    Not reported
    Methodology
    ML transcriptomic-age predictor; focused gene screen in aged human fibroblasts (donors aged 55, 65, 79); AAV-SRSF1 in aged mice
    Limitations
    Mouse and cell-line data only; no human in vivo data. Sample sizes, sexes, survival curves and epigenetic-clock magnitude not verified from the full paper (details here come from press coverage of the Wyss Institute release). Delivery, dosing and the splicing mechanism are unresolved; effects outside liver are proposed, not shown.
    04

    Citations & References

    Cite this paper

    Plesa AM, Jung S, Church GM, del Sol A, Wagers AJ, Mair WB (2026). Transcriptomic reprogramming screen identifies SRSF1 as a regulator of aging. Nature Aging. https://doi.org/10.1038/s43587-026-01234-8

    DOI

    10.1038/s43587-026-01234-8

    Source

    Publisher

    Journal

    Nature Aging

    05

    Indexing

    Topics

    reprogrammingrejuvenationsplicinglifespan

    Interventions

    partial-reprogramming
    PHS
    671
    / 1000
    T3
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