Early in her career, Ana Maria Cuervo, M.D., Ph.D., discovered chaperone-mediated autophagy (CMA)—a crucial cellular “self-cleaning” process that targets, digests, and recycles old proteins. Dr. Cuervo’s research has shown that CMA dysfunction is a key driver of aging and that declines in CMA—and the resulting buildup in waste material—is associated with Alzheimer’s, Parkinson’s, and other age-related diseases. 

Now, for the first time, Dr. Cuervo, Rabia Khawaja, Ph.D., and colleagues have used mice to compare CMA activity across all major organs in both males and females and to see how CMA activity changes with age. The results were published online on February 5 in Nature Aging. Among the results: In most organs, CMA decreases with age in both sexes, but the decline with age is generally more pronounced in males; and in many organs (e.g. brain, kidney, white adipose tissue) of young mice, CMA is more active in females than in males. The findings indicate that a therapy to bolster CMA and slow down aging will probably require personalized interventions specific to a person’s sex. In addition, knowing which body cells are more likely to age due to declines in CMA activity will enable scientists to better understand and predict the risk of diseases affecting those cell types.

Dr. Cuervo is distinguished professor of developmental & molecular biology and of medicine and is the Robert and Renee Belfer Chair for the Study of Neurodegenerative Diseases at Einstein, is co-director of Einstein’s Institute for Aging Research, and is a member of the National Cancer Institute-designated Montefiore Einstein Comprehensive Cancer Center and the Marion Bessin Liver Research Center. Dr. Khawaja is a senior post-doctoral fellow in Dr. Cuervo’s laboratory.