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Pathogen Control (Lidsky)

Simple Summary

  • Idea: Aging evolves to curb pathogen spread/persistence; finite lifespan limits epidemics. Senescent cells act as an antiviral “militia” when timed/cleared correctly.
  • Infection tradeoffs: In pathogen‑rich environments, longevity gains should increase infection risk unless combined with anti‑pathogen measures (e.g., vaccination/antivirals/barrier housing).

  • Population structure: Lidsky’s theory explains why lifespan varies with how a species lives and mixes (who meets whom, how often, how long): population structure changes epidemic dynamics, and that changes selection on lifespan.

    • High dispersal (birds/bats): Moving a lot and mixing across groups breaks long local transmission chains. Epidemics fizzle faster, so long life is less costly — helping explain unusual longevity in flyers.
    • Eusocial colonies (ants/bees/termites; naked mole rats): One queen, many workers; close kin structure. Colonies can isolate/cull infected workers quickly — a kind of colony‑level immunity — so aging programs can split (very long‑lived queens, short‑lived workers).
    • Synchronized migrations/semelparity (salmon): One big, same‑time spawn then death. Cohorts “reset” together, reducing pathogen carryover to juveniles; programmed post‑spawn death curbs transmission.

  • Comparative/experimental signature: longevity wins without infection costs under pathogen challenge weigh against this view.

Conflicts With Other Theories

  • Epigenetic Information (Sinclair)
    • Sinclair: Partial reprogramming can rejuvenate without infection penalties.
    • PC: under pathogen challenge, rejuvenation should incur infection costs unless anti‑pathogen control is added.
  • SENS Damage Repair (de Grey)
    • SENS: Repairs extend lifespan independent of infection ecology.
    • PC: In high‑burden contexts, repairs alone risk increased pathogen persistence unless co‑applied with anti‑pathogen strategies.
  • Resilience / Criticality (Fedichev)
    • Resilience: Hazard falls by improving system dynamics even without infection changes.
    • PC: Reducing pathogen burden is the primary driver; resilience without infection change should be limited.
  • Classic Models (Medawar, Williams, Hamilton, Kirkwood)
    • Classics: Longevity gains need not show infection costs; tradeoffs are resource‑based.
    • PC: Longevity gains often trade off with infection ecology; lifespan is selected to constrain epidemics.
  • Bioelectric / Morphogenetic Control (Levin)
    • Levin: Pattern control is upstream; rejuvenation shouldn’t inherently impose infection costs.
    • PC: under pathogen challenge, pattern‑based gains still face infection penalties unless anti‑pathogen measures co‑apply.
  • Longevity Bottleneck (Various Proponents)
    • Bottleneck: Chronic damage‑response activation is intrinsic and central.
    • PC: Chronic activation is often maintained by infections; anti‑pathogen interventions should calm pathways/hazard.

Questions

Do longevity gains actually show infection tradeoffs in pathogen‑rich environments?

Often, studies run in ultra‑clean SPF facilities, so direct evidence is limited; most interventions haven’t been tested head‑to‑head under pathogen challenge with infection endpoints. Where host‑defense is taxed or dosing is immunosuppressive, tradeoffs do appear: for example, transplant‑style mTOR inhibitor regimens increase infections, while lower, TORC1‑selective doses in older adults improved vaccine responses and reduced infections — showing direction depends on context and dose ††. “Dirty mice”/rewilding work shows that moving from SPF to natural exposure reshapes immune tone and can blunt or flip effects seen in clean rooms ††.

What’s missing are decisive, lifespan‑oriented tests under deliberate pathogen challenge. That’s why the discriminators here propose running OSK and stacked repairs with and without anti‑pathogen plans, and comparing naturalistic exposure against resilience arms with pre‑registered infection endpoints (OSK under infection; Stacked repairs under infection; Pathogen burden vs resilience). If clean, penalty‑free longevity gains persist under pathogen challenge, that weakens Pathogen Control; if penalties appear unless anti‑pathogen measures co‑apply, it supports it.

Sources

  • Tweet (seed): https://vxtwitter.com/lidskypeter/status/1962526281863508444
  • PNAS 2020 (lifespan setpoints): https://doi.org/10.1073/pnas.1920988117
  • TREE 2022 (PC hypothesis): https://doi.org/10.1016/j.tree.2022.08.003