Miguel Bronchud, Veteran Cancer Clinician, Researcher, Co-Founder and ex Advisory Board at Regenerative Medicine Solutions, shared on LinkedIn:
“‘Lysosomes’ are the cellular ‘guardians of healthy proteins’? Or the storage organelles that accumulate as we age potentially toxic metabolites that they are unable to digest? Or maybe an excellent example of biological clock for aging detection?
See Science’s recent publication: ‘Changes in lysosomal metabolites are associated with both aging organs and lysosomal storage diseases’
Editorial Review By: Jeeyoon Na and Anne Brunet
Lysosomes are central to cellular metabolism, and their function declines substantially in many degenerative diseases and during aging.
But how content of these organelles changes with age and whether these changes differ across tissues remain unknown.
On page 488 of a recent SCIENCE issue, Puszynska et al. describe a multitissue atlas of lysosomal metabolites during aging: A. M. Puszynska et al., Science 393 eady0832 (2026).
Several metabolites accumulate with age across multiple tissues in several mammalian species. Notably, those that increase with age also accumulate in lysosomal storage disorders-devastating diseases that predominantly affect children-providing an intriguing connection between these diseases and aging.
Lysosomes are present in most cells across many species, and their functions include degrading and recycling cellular macromolecular waste, as well as sensing nutrients. Have we largely missed their roles in aging and elderly people?
Mutations in genes encoding lysosomal proteins lead to lysosomal storage disorders that manifest early in life and are often fatal. Pediatricians have known about these disorders for decades. But what about geriatricians?
These conditions are characterized by abnormal accumulation of specific metabolites in the lysosome. Lysosomal function also declines in aging and in several age-associated diseases .
For example, defective repair of compromised lysosomes or impaired lysosomal acidification contributes to the accumulation of toxic protein aggregates during aging and in Alzheimer’s disease .
Although age-dependent metabolic changes across different tissues have been profiled the main metabolic changes specific to lysosomes are often uncharacterized.
Puszynska et al. used a genetically modified mouse line called ‘LysoTag’ , strange unhappy mice , which allows rapid isolation of tagged lysosomes from tissues. Lysosomes from young and old LysoTag mice were isolated from many tissues, and their metabolite content was measured with mass spectrometry.
Surprisingly, lysosomes from the brain, heart, skeletal muscle, and white adipose tissue of old mice showed accumulation of metabolites belonging to the glycerophosphodiester (GPD) class as well as cystine. These metabolites are also known to increase in lysosomal storage disorders.
GPDs accumulate in Batten disease, and cystine accumulates in cystinosis .
Signatures of aging and disease in a single organelle.”
Other articles featuring Miguel Bronchud on OncoDaily.