Hormesis and aging in Caenorhabditis elegans.
Hormesis has emerged as an important manipulation for the study of aging. Although hormesis is manifested in manifold combinations of stress and model organism, the mechanisms of hormesis are only partly understood. The increased stress resistance and extended survival caused by hormesis can be manipulated to further our understanding of the roles of intrinsic and induced stress resistance in aging. Genes of the dauer/insulin/insulin-like signaling (IIS) pathway have well-established roles in aging in Caenorhabditis elegans. Here, we discuss the role of some of those genes in the induced stress resistance and induced life extension attributable to hormesis. Mutations in three genes (daf-16, daf-18, and daf-12) block hormetically induced life extension. However, of these three, only daf-18 appears to be required for a full induction of thermotolerance induced by hormesis, illustrating possible separation of the genetic requirements for stress resistance and life extension. Mutations in three other genes of this pathway (daf-3, daf-5, and age-1) do not block induced life extension or induced thermotolerance; daf-5 mutants may be unusually sensitive to hormetic conditions.
Cypser
James R
JR
University of Colorado, Institute for Behavioral Genetics, Box 447 Boulder, CO 80309, Fedex, 1480 30th St., Boulder, CO 80303, USA. jrcypser@colorado.edu
Tedesco
Pat
P
Johnson
Thomas E
TE
D000375:Aging / Q000235:genetics*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D031204:Caloric Restriction; D051858:Forkhead Transcription Factors; D017238:Genes, Helminth / Q000235:genetics; D006358:Hot Temperature; D007328:Insulin / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008136:Longevity / Q000235:genetics; D009154:Mutation; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013312:Stress, Physiological / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; C410905:DAF-12 protein, C elegans; C116661:DAF-18 protein, C elegans; D051858:Forkhead Transcription Factors; D007328:Insulin; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D007335:Insulin-Like Growth Factor II