Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging

Protein damage contributes prominently to cellular aging. To address whether this occurs at a specific period during aging or accumulates gradually, we monitored the biochemical, cellular, and physiological properties of folding sensors expressed in different tissues of C. elegans. We observed the age-dependent misfolding and loss of function of diverse proteins harboring temperature-sensitive missense mutations in all somatic tissues at the permissive condition. This widespread failure in proteostasis occurs rapidly at an early stage of adulthood, and coincides with a severely reduced activation of the cytoprotective heat shock response and the unfolded protein response. Enhancing stress responsive factors…

• NI
  National Institutes of Health
• DF
  Directorate for Biological Sciences
• NI
  National Institute of General Medical Sciences
• NI
  National Institute of Child Health and Human Development
• NC
  National Center for Research Resources