Aging

Autophagy in physiological aging

We have found that both chaperone-mediated autophagy (CMA) and endosomal microautophagy (eMI) decrease with age. We are investigating the molecular mechanisms behind that decrease. In the case of CMA, we have identified a decrease in the levels of the receptor with age, that when we mimic it in young animals results in multiple-tissue degeneration, metabolic dysregulation, loss of stemness and higher propensity to cancer. We are now using genetic and chemical approaches to revert the age-related defect on CMA and explore the impact on life- and health-span and on the resistance to stress.

  • Chaperone-mediated autophagy sustains haematopoietic stem-cell function. Dong S, Wang Q, Kao YR, Diaz A, Tasset I, Kaushik S, Thiruthuvanathan V, Zintiridou A, Nieves E, Dzieciatkowska M, Reisz JA, Gavathiotis E, D’Alessandro A, Will B, Cuervo AM. Nature, 2021. doi: 10.1038/s41586-020-03129-z

  • Defective recruitment of motor proteins to autophagic compartments contributes to autophagic failure in aging. Bejarano E, Murray J, Wang X, Pampliega, O, Yin D, Patel B, Yuste A, Wolkoff A, Cuervo AM. Aging Cell, 2018. doi: 10.1111/acel.12777

  • Loss of hepatic chaperone-mediated autophagy accelerates proteostasis failure in aging. Schneider S, Villarroya J, Diaz A, Patel B, Urbanska AM, Thi MM, Villarroya F, Santambrogio L, Cuervo AM. Aging Cell, 2015. doi: 10.1111/acel.12310

  • Proteostasis and aging. Kaushik S, Cuervo AM. Nat Med, 2015. doi: 10.1038/nm.4001