Misfolded proteins, aggregates, and inclusion bodies are hall-marks of the cytopathology of neurodegenerative disorders including Huntington’s disease, Amyotropic lateral sclerosis, Parkinson’s disease, Prion diseases, and Alzheimer’s disease. The appearance of proteins with altered folded states is regula-ted by the protein folding quality control machinery and age-dependent. We have identified an unexpected molecular link between metabolic state, accumulation of damaged proteins, the heat-shock response and chaperones, and longevity