In this episode, host Buck Joffrey dives into the basic science of aging with Judith Frydman, a world leader in proteostasis research. The conversation explains how failures in protein folding and quality control accumulate with age, driving neurodegenerative disease and broader biological decline.

Key Points:

Aging is closely tied to the gradual collapse of the cell’s protein quality-control systems. As proteostasis fails, misfolded proteins accumulate, fuelling neurodegeneration and systemic decline. Restoring protein folding and clean-up pathways could be a powerful route to extending healthspan.

Proteins as the engines of life: Proteins do almost everything in cells, but they must fold into precise 3D shapes; misfolding disrupts function and accumulates with age 

• Misfolded proteins and disease: Aggregates of damaged proteins form plaques seen in Alzheimer’s, Parkinson’s, and other neurodegenerative diseases, linking protein errors directly to aging pathology 
• Proteostasis: cellular quality control: Cells rely on chaperones, degradation systems (proteasome), and autophagy to keep proteins functional; this entire network weakens during aging 
• TRiC/CCT- a key folding machine: The TRiC chaperonin helps fold complex, essential proteins; its activity declines with age and is associated with neurodevelopmental and neurodegenerative disorders 
• A vicious cycle of aging: Misfolded proteins overwhelm cleanup systems, impair mitochondria, reduce cellular energy, and further weaken protein maintenance—creating a self-reinforcing loop 
• Paths to intervention: Promising strategies include boosting autophagy, improving lysosomal and proteasome function, enhancing chaperones like TRiC, and slowing protein synthesis via lifestyle or drugs.