Autophagy decline during ageing: Molecular regulation, tissue specificity, and therapeutic potential.
Level 5 - mechanism / opinion, no new human data
Narrative review of mechanistic and preclinical studies without new clinical data.
PubMed 42224830 · doi:10.1016/j.prp.2026.156568
What was done
This narrative review synthesized preclinical literature regarding the mechanisms of age-related autophagy decline, its tissue-specific manifestations across cardiovascular, neurodegenerative, metabolic, muscular, and ocular systems, and experimental strategies (including mTOR inhibition, AMPK activation, polyphenols, caloric restriction, and exercise) aimed at restoring autophagic flux.
What was found
The abstract reports no quantitative data or effect sizes. It describes that age-related autophagy decline is driven by altered nutrient-sensing pathways (AMPK, mTOR), impaired transcription factor activity (TFEB, FOXO), and decreased lysosomal competence. While preclinical models demonstrate that pharmacological and lifestyle interventions can restore autophagic function and alleviate age-related pathology, no clinical trial data are currently available to confirm their safety and therapeutic efficacy in humans.
Why it matters
It provides a consolidated overview of the molecular pathways governing autophagy in aging tissues, highlighting the need to bridge the gap between preclinical promise and human clinical evaluation.
Limits
The publication is a narrative review with no primary empirical data, quantitative synthesis, or systematic search methodology reported in the abstract. Evidence is restricted to preclinical models, with a complete absence of human clinical safety and efficacy data.
Cited by
- supports Both caloric restriction and exercise stimulate cellular autophagy to clear damaged protein aggregates and DNA fragments from cells.