ABSTRACT
Introduction 68
Lifespan Regulation in C. elegans 69
Aging of C. elegans 69
Stress, Hormesis, and Lifespan in C. elegans 69
Insulin/IGF-I Signaling and Lifespan Regulation 70 Insulin/IGF-I Signaling Pathway and
Stress Resistance 73
DAF-16 Transcription Target 76
Reproductive System and Lifespan 77
Nervous System and Lifespan 78
Mitochondrial Electron Transport
and Lifespan 78
Lifespan Regulation in Drosophila 81
Lifespan Regulation in Mammals 83
Replicative Lifespan and Oxidative Stress 85
Conclusion 86
References 86
INTRODUCTION
The lifespan of metazoans can be extended by environmental conditions: caloric
restriction (CR) in a wide range of organisms (1), low temperature in some
poikilothermic animals (2), and low oxygen concentrations in the nematode
Caenorhabditis elegans (3). The mechanisms by which each condition slows
the aging rate have not yet been fully elucidated. Function of CR has been pos-
tulated as hormonal changes, altered gene expression, lowered metabolic rate,
and a reduced generation rate of mitochondrial reactive oxygen species (ROS).
Lifespan could also be lengthened by environmental perturbations. Hormesis is
a phenomenon occurring when agents that are harmful at high doses or over
long periods, actually produce beneficial effects, such as lifespan extension,
when used at low doses or over short periods. C. elegans shows lifespan-
extension hormesis when exposed to low doses of radiation (4) or short-term
heat (5), hyperoxia (6), or hyperbaric oxygen (7). These treatments are associated
with adaptive resistance to lethal thermal or oxidative stress, and the gene
expression of stress-defense proteins (5,6,8).
