Mechanism

Proteostasis

Proteostasis is the cell's system for keeping proteins correctly made, folded and cleared. Its gradual failure is a recognised hallmark of aging.

Also known as: proteostasis, protein homeostasis, loss of proteostasis

What proteostasis is

Proteostasis (protein homeostasis) is the network of processes that keeps a cell's proteins in balance — controlling their synthesis, correct folding, trafficking and timely degradation. When a protein is damaged or misfolded, proteostasis machinery either refolds or disposes of it.

Why it matters for longevity

Loss of proteostasis is one of the hallmarks of aging. As we age, misfolded and aggregated proteins accumulate — a process central to neurodegenerative diseases such as Alzheimer's and Parkinson's. A key clearance route is autophagy, and several pro-longevity interventions that act via mTOR work partly by enhancing this protein quality control.

What the evidence shows

The link between failing proteostasis and age-related disease is well supported by decades of molecular and animal research. Interventions that boost proteostasis (fasting, mTOR inhibition) improve outcomes in models, but human anti-aging proof is still limited.

Bottom line

Keeping the protein quality-control system working is a core longevity mechanism — credible target, strong mechanistic evidence, human interventions still maturing.

Sources & references

  1. Hipp MS, Kasturi P, Hartl FU. The proteostasis network and its decline in ageing. Nat Rev Mol Cell Biol. 2019. doi:10.1038/s41580-019-0101-y
  2. López-Otín C, et al. Hallmarks of aging: an expanding universe. Cell. 2023. doi:10.1016/j.cell.2022.11.001

Related terms

Educational information, not medical advice. Evidence ratings follow our methodology.