# Loss of proteostasis

Loss of proteostasis is one of the established hallmarks of aging and describes the age-related decline of the protein quality control network. Chaperones become less efficient, the proteasome and autophagy slow down, and misfolded or aggregation-prone proteins accumulate. The resulting proteotoxicity contributes to neurodegenerative disorders, cardiac amyloidosis, and cellular dysfunction across tissues, making proteostasis enhancers an active longevity research target.

## Sources

- Klaips CL, Jayaraj GG, Hartl FU. (2018). Pathways of cellular proteostasis in aging and disease. Journal of Cell Biology. https://doi.org/10.1083/jcb.201709072
- López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. (2023). Hallmarks of aging: An expanding universe. Cell. https://doi.org/10.1016/j.cell.2022.11.001

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_Canonical: https://longevity-germany.com/en/glossary/loss-of-proteostasis · Part of Longevity Cities · Updated 2026-01-15_