BMG Faculty Candidate Seminar
Department of Biochemistry and Molecular Genetics
“Atlas of Lysosomal Aging: Revealing a Molecular Clock of Storage-Associated Metabolites”
Anna M. Puszynska, PhD
Postdoctoral Fellow
Whitehead Institute for Biomedical Research, MIT
Cambridge, MA
Abstract:
Lysosomal dysfunction is a well-recognized feature of aging, yet its systematic molecular investigation remains limited. I employed a suite of tools for rapid lysosomal isolation to construct a multi-tissue atlas of the metabolite changes lysosomes undergo during aging. Aged lysosomes in the brain, heart, muscle and white adipose tissue accumulate glycerophosphodiesters and cystine, metabolites that are causally linked to juvenile lysosomal storage disorders, Batten disease and cystinosis. Levels of these metabolites increase linearly with age, preceding organismal decline. Caloric restriction, a lifespan-extending intervention, mitigates these changes in the heart and muscle but not the brain. These findings link lysosomal storage disorders to aging-related dysfunction, uncover a metabolic lysosomal “aging clock,” and open avenues for the mechanistic investigation of how lysosomal functions deteriorate during aging and in age-associated diseases.
Hosts: Drs. Ali Shilatifard, Chairman, and Issan Ben-Sahra, Associate Professor, Department of Biochemistry and Molecular Genetics
Linda Jackson
Email