In short
Proteostasis (protein homeostasis) is the network of cellular machinery — chaperones, the ubiquitin-proteasome system, and autophagy — that folds, refolds, and degrades proteins to keep the cell's protein pool functional.
Proteins must fold into precise three-dimensional shapes to function, and this process can go wrong constantly, especially under stress from heat, oxidative damage, or aging itself. Molecular chaperones (such as heat shock proteins) help proteins fold correctly or refold after damage. Proteins that cannot be salvaged are tagged with ubiquitin and degraded by the proteasome, or cleared in bulk via autophagy.
Proteostasis capacity declines with age: chaperone expression drops, proteasome activity falls, and misfolded or aggregated proteins accumulate faster than they can be cleared. This decline is central to several well-characterized neurodegenerative diseases — amyloid-beta plaques and tau tangles in Alzheimer's disease, and alpha-synuclein aggregates in Parkinson's disease, are both protein-aggregation disorders that become dramatically more common with age.
Interventions that activate autophagy or the heat-shock response (including caloric restriction and fasting, which upregulate autophagy through AMPK/mTOR signaling) are studied partly on the premise that they support proteostasis, and this is well established in cell and animal models. There is no approved human drug that directly and selectively restores general proteostasis capacity as a therapeutic strategy; current human evidence is limited to the downstream biomarker and disease-specific therapies (e.g., drugs targeting amyloid clearance in Alzheimer's), not a general proteostasis-boosting intervention.