Atlas of lysosomal aging reveals a metabolite signature shared with lysosomal storage disorders.
AM, P., TP, N., AL, C., A, A., JM, R., KA, S., JC, C., T, T., GY, L., & S, L. (2026). Atlas of lysosomal aging reveals a metabolite signature shared with lysosomal storage disorders.. Science (New York, N.Y.). https://doi.org/10.1126/science.ady0832
AM P, TP N, AL C, A A, JM R, KA S, et al. Atlas of lysosomal aging reveals a metabolite signature shared with lysosomal storage disorders.. Science (New York, N.Y.). 2026; doi: 10.1126/science.ady0832
AM P, TP N, AL C, et al. Atlas of lysosomal aging reveals a metabolite signature shared with lysosomal storage disorders.[J]. Science (New York, N.Y.). 2026. DOI: 10.1126/science.ady0832.
@article{am2026,
author = {Puszynska AM and Nguyen TP and Cangelosi AL and Armani A and Roberts JM and Singh KA and Cameron JC and Tseyang T and Liu GY and Lai S},
title = {Atlas of lysosomal aging reveals a metabolite signature shared with lysosomal storage disorders.},
journal = {Science (New York, N.Y.)},
year = {2026},
doi = {10.1126/science.ady0832},
note = {PMID: 42531412},
}
TY - JOUR AU - Puszynska AM AU - Nguyen TP AU - Cangelosi AL AU - Armani A AU - Roberts JM AU - Singh KA AU - Cameron JC AU - Tseyang T AU - Liu GY AU - Lai S TI - Atlas of lysosomal aging reveals a metabolite signature shared with lysosomal storage disorders. T2 - Science (New York, N.Y.) PY - 2026 DO - 10.1126/science.ady0832 AN - PMID:42531412 ER -
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.