ABSTRACT
Calorie restriction-triggered delayed senescence in S. cerevisiae requires expression of an intact nicotinamide adenine dinucleotide (NAD) synthesis pathway and the NAD-dependent deacetylase Sir2. Resveratrol mimics the lifespan-extending effects of Calorie restriction in Saccharomyces cerevisiae by activating Sir2, but does so independently of nicotinamidase expression, as it is similarly effective in a PNC1-null mutant. Neurodegenerative disorders constitute a devastating class of diseases related to aging. Neurons are subject to two types of self-destruction: apoptosis by canonical, caspase-mediated signaling programs, and axonal degeneration, which is a compartmentalized, orderly process that is triggered when an axon is mechanically cut from cell body or injured by chemical or other means. The multiplicity of resveratrol targets is an indication of the challenge posed in developing bioavailable resveratrol analogs that conserve the bioactivity of the polyphenolic phytoalexin in mammalian systems. Dispensing with some features of resveratrol bioactivity may be beneficial.
