Autophagy Protects Murine Preputial Glands Against Premature Aging and Controls Their Sebum Phospholipid and Pheromone Profile

The study investigated the role of autophagy in murine preputial glands, revealing that autophagy delayed age-related ductal ectasia, influenced lipid droplet morphology, and facilitated the dissolution of mature sebocytes during holocrine secretion. Single-cell RNA sequencing showed downregulation of genes involved in lipid metabolism and oxidative stress response in ATG7-deficient glands. Lipid analysis indicated decreased levels of most phospholipid classes and an accumulation of diacyl glycerides in mutant glands. Mass spectrometric imaging confirmed reduced phosphatidylcholine species and a significant decrease in the pheromone palmityl acetate. Thus, autophagy was crucial for gland homeostasis, lipid and fatty acid metabolism, and pheromone production.