🧬 Aging Wiki

2026-07-21

2 min read

[2026-07-21] ingest | Efimov 2026 somatic-mutation lifespan-bound model

User-supplied paper ingested through the seeder → independent verifier → propagation workflow: Efimov et al., “Somatic mutations impose an entropic upper bound on human lifespan,” npj Aging (2026), doi:10.1038/s41514-026-00421-6, PMID 42350444. The accessible publisher version remains an unedited Article-in-Press manuscript; final-version drift should be checked after production.

Added

  • studies/efimov-2026-somatic-mutations-lifespan-bound.md — verified end-to-end against the open-access manuscript and supplement. Records the 16-population demographic input, 229 cellular mutation samples, inferred mutation-lethality construction, Models I–IIIC, simulation accounting, organ thresholds, sensitivity analysis, and reproducibility limits.

Propagated

  • hypotheses/somatic-mutation-theory-of-aging.md — added Efimov 2026 to key-evidence-for, historical development, evidence assessment, status rationale, predictions, and gaps. Status remains contested: the paper quantifies the theory but assumes rather than demonstrates mutation-driven cell death.
  • processes/somatic-mutation-accumulation.md — added a clearly model-derived causal-interpretation paragraph and refreshed literature recency without treating the paper as a new empirical mutation-rate measurement.
  • hallmarks/genomic-instability.md — navigational link only, preserving the hallmark page as an overlay rather than duplicating study claims.

Verifier-caught corrections

  • Split the empirical 79-year Swiss median from the global 122-year documented maximum.
  • Replaced the claim that the full counterfactual is falsifiable: individual parameters and tissue predictions are testable, but the mutation-only organismal counterfactual is not conventionally falsifiable.
  • Clarified that the four-margin lower FrĂ©chet expression is a valid pointwise envelope but need not be jointly attainable.
  • Separated directly fitted mutation slopes from ratio-inferred cardiomyocyte-indel and liver-progenitor inputs.
  • Distinguished the analytical background values (1,759/29,221 years) from the nearly matching finite-simulation Model IIIA values (1,755/29,147 years).

Evidence judgment and gaps

  • Central independence outputs (median 156 years; operational 10^-5-survival time 470 years) and pointwise dependence envelopes (146–194; 210–557 years) were confirmed, but remain conditional simulations rather than observed lifespans.
  • The qualitative post-mitotic-versus-proliferative tissue ordering is more robust than the exact ages; per-mutation lethality, organ reserve thresholds, omitted sublethal/clonal effects, and systemic coupling remain load-bearing gaps.
  • A 2021–2026 PubMed + Europe PMC recency refresh surfaced Koch et al. 2026 (DREAM repression/mutation burden), Jeffries et al. 2025 (ageing human brain single-cell genomics), and the 2025 SMaHT Network programme. None overturns the contested status: Koch reports reduced brain mutation accumulation after DREAM knockout but no lifespan endpoint; the latter two are queued as parameter/data-atlas candidates rather than silently propagated from abstracts.
  • The Cagan 2022 study companion page remains a pre-existing missing-page candidate; no new bronchial-basal-cell link was left dangling.

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