Genetics, Redox Signaling, Oxidative Stress, and Apoptosis in Mammalian Aging

摘要

THE FIELD OF AGING RESEARCH has now entered a rapid phase of discovery. The most dramatic findings have been associated with the extension of lifespan in simple organisms, such as C. elegans, S. cerevisiae, and Drosophila. The question that now permeates the field is "Can these findings be extended to mammals?" Only two interventions- caloric restriction and dwarf ism-have achieved life extension to an extent that compares with findings obtained in the simpler organisms. However, there is tantalizing evidence that a deeper understanding of mammalian aging is at hand. Several interventions, such as overexpression of antioxidant enzymes (15), p66Shc deletion (9), and manipulations of insulin/IGF 1 axis (1) have produced extension of lifespan in the absence of the overt changes in body composition observed in caloric restriction or dwarf animals. Interestingly, most of these interventions appear to be associated with an increase in stress resistance. In this forum issue of ARS, the relevance of genetics, redox balance, oxidative stress, and apoptosis to mammalian aging is examined through a spectrum of viewpoints