Proteasomal Regulation of the Hypoxic Response Modulates Aging in C. elegans

Abstract

Anti-Aging: Several human neurodegenerative diseases, such as Alzheimer's and Huntington's, are caused by aberrant protein aggregation. These disorders typically develop after the fifth decade of life, suggesting a connection with the aging process. In a number of different species, life span can be extended by dietary restriction and reduced insulin and insulin-like growth factor–1 (IGF-1) signaling. These pathways can also decrease toxic protein aggregation, mechanistically linking aging with proteotoxic diseases. While searching for regulators of proteotoxicity in Caenorhabditis elegans , Mehta et al. (p. 1196 , published online 16 April) found that reduction of the von Hippel–Lindau tumor suppressor homolog VHL-1 significantly increased life span and enhanced resistance to proteotoxicity. VHL-1 is an E3 ubiquitin ligase that negatively regulates the hypoxic response, and animals grown under hypoxic conditions lived longer. This alternative longevity pathway was distinct from both dietary restriction and insulin/IGF-1–like signaling.