Source: Wiki notes (autophagy/) + PubMed companion-animal literature

Local report: src/tasks/task_output_autophagy_mammals_longevity_22_JULY_2026.md

Summary

Autophagy is a necessary mediator of multiple longevity interventions (yeast → worms → flies → mice). Companion dogs are now the strongest non-lab mammalian system testing this at lifespan/healthspan scale (Dog Aging Project; TRIAD rapamycin RCT). Direct feline autophagy–longevity data remain sparse.

Core claim: Age-associated decline in competent autophagic flux drives tissue failure. Restoring flux (not merely elevating LC3-II) is a plausible healthspan lever in dogs and, by homology, cats.

Mechanistic Core

Autophagy delivers cytoplasmic cargo to lysosomes for degradation/recycling.

Type Route Aging relevance
Macroautophagy Autophagosome → lysosome Proteostasis, organelle QC
Mitophagy PINK1/Parkin, BNIP3 Limits ROS, mtDNA stress
CMA KFERQ via LAMP-2A Declines with age
Selective autophagy p62 adapters Senescence (p16/p21 clearance)

Initiation logic (conserved in dog/cat):

Nutrient/growth → mTORC1 ON  → ULK1 repressed → autophagy OFF
Energy stress   → AMPK ON    → ULK1 active     → autophagy ON
NAD+/SIRT1      → Atg/FOXO/TFEB deacetylation  → flux boost

Causal chain: autophagy ↔ longevity

  1. Genetic loss of ATG genes shortens lifespan and produces aging-like phenotypes
  2. Longevity interventions (CR, rapamycin, spermidine, SIRT1, reduced IIS) require autophagy
  3. Aging reduces autophagic capacity (ATG expression, lysosomal acidification, CMA, epigenetics)

Flux, not snapshots. Elevated LC3-II can mean induction or blocked clearance. Longevity-relevant phenotype = completed cargo → lysosome → recycling (ideally lower p62 when flux is competent).

Why Dogs (and Cats)