Autophagy and longevity: Evolutionary hints from hyper-longevous mammals
Andrea G. Locatelli and Simone Cenci
Additional article information
Abstract
Autophagy is a fundamental multi-tasking adaptive cellular degradation and recycling strategy. Following its causal implication in age-related decline, autophagy is currently among the most broadly studied and challenged mechanisms within aging research. Thanks to these efforts, new cellular nodes interconnected with this phylogenetically ancestral pathway and unexpected roles of autophagy-associated genetic products are unveiled daily, yet the history of functional adaptations of autophagy along its evolutive trail is poorly understood and documented. Autophagy is traditionally studied in canonical and research-wise convenient model organisms such as yeast and mice. However, unconventional animal models endowed with extended longevity and exemption from age-related diseases offer a privileged perspective to inquire into the role of autophagy in the evolution of longevity. In this mini review we retrace the appearance and functions evolved by autophagy in eukaryotic cells and its protective contribution in the pathophysiology of aging.
Full paper, open access
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9807614/
1 Like
Good overview of scientific efforts at selectively increasing autophagy:
1 Like
An interesting new paper from Tim Sargeant’s group in Australia:
Autophagy across tissues of aging mice
Julian M Carosi, Alexis Martin, Leanne K Hein, Sofia Hassiotis, Kathryn J Hattersley, Celia Fourrier, Julien Bensalem and Timothy J Sargeant
Autophagy is a waste-disposal pathway that protects against age-related pathology. It is widely accepted that autophagy declines with age, yet role that sex and diet-related obesity play during aging remain unknown. Here, we present the most comprehensive in vivo study of autophagic flux to date. We employed transgenic mice overexpressing tandem-florescent LC3B (RFP-GFP-LC3B) to measure autophagic flux in the blood (PBMCs), heart, and motor cortex of aging mice that were fed regular chow or a high-fat diet for 6-, 12- or 18-months. In male mice, aging reduced autophagic flux in the heart and brain, but increased it in the blood. Age-dependent changes in female autophagic flux was less pronounced. Autophagic flux was modified by a high-fat diet in the blood and heart of male but not female mice. Overall, we uncovered sexual dimorphisms that underpin how autophagy changes with age across different tissues and in response to a high-fat diet.
bioRxiv. posted 11 September 2024, 10.1101/2024.09.11.612427
http://biorxiv.org/content/early/2024/09/11/2024.09.11.612427
3 Likes
