Atlas of lysosomal aging reveals a metabolite signature shared with lysosomal storage disorders

Science 2026

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Authors: Anna M. Puszynska, Thao P. Nguyen, Andrew L. Cangelosi, Andrea Armani, Justin M. Roberts, Kristin A. Singh, James C. Cameron, Tenzin Tseyang, Grace Y. Liu, Steven Lai, Hans‐Georg Sprenger, Jason Yang
+12 more William Colgan, Jibril F. Kedir, Kathrin M. Kajderowicz, Theodore K. Esantsi, Yuancheng Ryan Lu, Millenia Waite, Tenzin Kunchok, Caroline A. Lewis, Fabian Schulte, George W. Bell, David M. Sabatini, Jonathan S. Weissman
DOI: 10.1126/science.ady0832
Cited by: 3
References: 101

Abstract

Lysosomal dysfunction is a well-recognized feature of aging. Here, we used a suite of tools for rapid lysosomal isolation to construct a multitissue atlas of the metabolite changes lysosomes undergo during aging. Aged lysosomes in brain, heart, muscle, and white adipose tissue accumulated glycerophosphodiesters and cystine, metabolites that are causally linked to juvenile lysosomal storage disorders, Batten disease, and cystinosis. Levels of these metabolites increased linearly with age, preceding organismal decline. Caloric restriction, a lifespan-extending intervention, mitigated these changes in the heart and muscle but not the brain. Our findings link lysosomal storage disorders to aging-related dysfunction and open avenues for the mechanistic investigation of how lysosomal functions deteriorate during aging and in age-associated diseases.

Fields of Study & Subjects

Biomedical Research and Pathophysiology Lysosomal Storage Disorders Research Calcium signaling and nucleotide metabolism

Publication details

Journal / source
Science
Publisher
American Association for the Advancement of Science (AAAS)
Volume
393
Issue
6810
Pages
eady0832–eady0832
Publication date
30 July 2026
Language
EN