Cellular stress and protein misfolding during aging.

Cells are under constant onslaught from several intrinsic and extrinsic stressors, which lead to the occurrence and accumulation of molecular damage, functional impairment, aging, and eventual death. Protein misfolding is both a cause and a consequence of increased cellular stress. An age-related failure of the complex systems for handling protein misfolding results in the accumulation of misfolded and aggregated proteins, and consequent conformational diseases. However, some misfolded proteins have been found to be both toxic and, in some cases, protective, highlighting the various complex, dynamic, and interdependent mechanisms at play. Molecular mechanisms are being elucidated for the occurrence of protein misfolding and for its prevention by chaperones and various pathways of degradation. Insights from the knowledge about proteodynamics are likely to impact future interventional strategies to counter stress and to promote healthy aging by preventing and/or treatment of protein conformational diseases.