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    PAPER GRONSKPreclinical mechanistic study2026

    Caloric restriction modulates genome-wide somatic mutation in mice

    Shows that somatic mutation accumulation — long treated as an irreversible substrate of aging — is reduced by caloric restriction across multiple mouse tissues, including the clock-like SBS5 mutational process, establishing genomic integrity as a diet-modifiable axis of aging.

    Evidence

    7/10

    Moderate Evidence

    Sample

    —

    subjects

    Duration

    —

    study period

    Journal

    Cell

    Sep 2026

    Authors

    Authorship

    Grońska-Pęski M, Acosta-Rodríguez V, Srinivasa A, Garrido A, Picciotto S, Green CB

    01

    Full Abstract

    Using high-fidelity duplex DNA sequencing of bulk liver, bulk kidney, hepatocytes and cerebellar neurons, caloric restriction in mice reduced genome-wide somatic mutation burdens across multiple tissues and cell types. CR reduced both substitution and insertion/deletion burdens, with magnitude varying across sample types, and decreased the activity of the single-base substitution process SBS5, which gives rise to most mutations in mammals. The mutation burden reduction from CR was greatest in transcriptionally inactive regions.

    02

    Key Findings

    1. 01

      CR lowered genome-wide somatic substitution and indel burden across liver, kidney, hepatocytes and cerebellar neurons

    2. 02

      CR decreased activity of SBS5, the mutational process responsible for most mammalian mutations

    3. 03

      Mutation-burden reduction was largest in transcriptionally inactive regions

    4. 04

      Effect size varied substantially by tissue and cell type

    03

    Structured Methods

    Study Design
    Preclinical mechanistic study
    Sample Size
    Not reported
    Study Duration
    Not reported
    Methodology
    High-fidelity duplex DNA sequencing of multiple tissues and sorted cell types in calorically restricted versus ad libitum fed mice
    Limitations
    Mouse-only. Causality for lifespan is not established, the result does not transfer automatically to CR mimetics or to time-restricted eating in humans, and somatic mutation burden is not measurable in routine clinical practice.
    04

    Citations & References

    Cite this paper

    Grońska-Pęski M, Acosta-Rodríguez V, Srinivasa A, Garrido A, Picciotto S, Green CB (2026). Caloric restriction modulates genome-wide somatic mutation in mice. Cell. https://doi.org/10.1016/j.cell.2026.08.013

    DOI

    10.1016/j.cell.2026.08.013

    Source

    Publisher

    Journal

    Cell

    05

    Indexing

    Topics

    caloric restrictiongenomic instabilityDNA repairsomatic mutation

    Interventions

    caloric restrictionintermittent fastingCR mimetics
    PHS
    671
    / 1000
    T3
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