Autophagy across tissues of aging mice

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.