# Loss of proteostasis

Loss of proteostasis is one of the established hallmarks of aging. The word 'proteostasis' means protein balance. This hallmark is the age-related decline of your protein quality-control network. Three things slip. Your chaperones (the folding helpers) get less efficient. Your proteasome and autophagy (the disposal systems) slow down. And misfolded, sticky proteins pile up. The resulting protein toxicity feeds disease. That includes brain disorders, heart amyloidosis, and cell trouble across tissues. That is why drugs to restore protein balance are an active longevity 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

---

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