# Chaperone-mediated autophagy (CMA)

Chaperone-mediated autophagy (CMA) is a precise way your cells recycle individual proteins. Unlike bulk autophagy, it does not wrap cargo in a vesicle. Instead, it ferries one tagged protein at a time straight into the lysosome (the cell's recycling chamber). The tag is a specific motif (a KFERQ-like sequence, recognized by its charge pattern rather than exact letters). A chaperone protein called HSC70 (always present, made by the HSPA8 gene) grabs that motif, with help from co-chaperones. The complex then docks at the lysosome through a receptor called LAMP2A, the one receptor that is enough for CMA. LAMP2A briefly clusters to form a channel the protein slides through. With age, LAMP2A levels at the lysosome fall, partly because changes in lysosomal fats speed its breakdown. That slows CMA and lets damaged, clump-prone proteins build up. Zhang and Cuervo (2008) showed the link in aged rodents: keeping liver LAMP2A high restored CMA, improved protein quality control, and preserved liver metabolism, causal evidence that CMA decline drives age-related proteostasis loss. The strongest evidence is in rodent liver and neurons. Human aging data are still limited. A 2024 review by Endicott cautioned that the size and universality of the decline vary by tissue and genetic background, so be careful extrapolating across species or cell types.

## Sources

- Zhang C, Cuervo AM. (2008). Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function. Nature Medicine. https://doi.org/10.1038/nm.1851
- Cuervo AM, Wong E. (2014). Chaperone-mediated autophagy: roles in disease and aging. Cell Research. https://doi.org/10.1038/cr.2013.153
- Endicott SJ. (2024). Chaperone-mediated autophagy as a modulator of aging and longevity. Frontiers in Aging. https://doi.org/10.3389/fragi.2024.1509400

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_Canonical: https://longevity-switzerland.com/en/glossary/chaperone-mediated-autophagy · Part of Longevity Cities · Updated 2026-06-22_