Proteostasis
The balance of protein synthesis, folding, and degradation — basis of cellular longevity
Definition
Proteostasis (protein homeostasis) is the set of cellular mechanisms that maintain correct folding, function, and timely degradation of all proteins. It is one of the central hallmarks of ageing: when lost, misfolded proteins accumulate forming toxic aggregates that underlie diseases such as Alzheimer's (β-amyloid, tau), Parkinson's (α-synuclein), Huntington's (huntingtin), ALS (SOD1, TDP-43), and frontotemporal dementia. Proteostasis declines inexorably with age.
Detailed explanation
The main protein quality control systems:
Molecular chaperones: proteins that assist correct folding and prevent aggregation. Heat Shock Proteins (HSP) are the best known; they are activated by thermal stress (sauna), caloric restriction, and exercise. HSP70, HSP90, and HSP60 (mitochondrial) are the most studied in longevity. Ubiquitin-proteasome system: marks damaged or dysfunctional proteins with ubiquitin chains, directing them to the 26S proteasome for rapid enzymatic degradation. Autophagy (macroautophagy, microautophagy, chaperone-mediated autophagy): massive degradation of proteins, organelles, and aggregates that the proteasome cannot handle. UPR response (Unfolded Protein Response): when the endoplasmic reticulum detects excess misfolded proteins, it slows global protein synthesis, increases chaperones, and, if unresolved, induces apoptosis.
Interventions that improve proteostasis: thermal hormesis (sauna induces HSP70 +50%, cryotherapy activates other mechanisms), intermittent fasting (induces deep autophagy), HIIT exercise, caloric restriction, spermidine supplementation (specifically induces autophagy), NAD+ (maintains mitochondrial function → fewer misfolded proteins), curcumin (potent HSP and autophagy activator).
Scientific sources
Interested in related treatments?
Generate My Protocol