ABSTRACT
All heterotrophs require food to survive, and food availability is subject to vast uctuations. The survival strategy of many organisms (microbes and animals alike) in times of plenty is to propagate as fast as possible, but how do these organisms respond when food sources are scarce? The response of many organisms to calorie or dietary restriction (CR/DR) is profound: they either switch priorities from reproduction to longevity, presumably to endure the current famine so that they can reproduce again once conditions improve, or attempt to extend the amount of time during which they remain capable of reproduction, either way resulting in longevity. CR causes widespread physiological and metabolic changes, intended to utilize what limited food is available to its fullest extent and stave off age-associated deterioration as long as possible. Surprisingly, this response to nutrient limitation must have
14.1 Introduction ................................................................................................299 14.2 Calorie Restriction in Budding Yeast .........................................................300 14.3 Mitochondria and Aging .............................................................................302 14.4 CR Mimicry and Pathways Involved in Yeast Longevity ...........................302 14.5 Physiological Impact of High Metabolic Rate during Calorie
Restriction ..............................................................................................306 14.6 Stress Resistance and Hormesis during CR ...............................................307 14.7 Autophagy and Mitophagy during CR and Nutrient Limitation ................309 14.8 Sirtuins, Metabolite Flux, and the Metabolic State of the Cell .................. 310 14.9 Mitochondrial and Nuclear Genome Stability during Aging ..................... 312 14.10 Present and Future Direction of CR, Mitochondria, and Life Span
Studies in Budding Yeast ............................................................................ 313 References .............................................................................................................. 313
evolved in an ancient precursor to heterotrophic eukaryotes, since many elements of the nutrient limitation response are conserved from the single-celled budding yeast Saccharomyces cerevisiae all the way up to mammals, and some elements are even evident in eubacteria. Examples of longevity machinery conserved from yeast to man include enzymes, such as the sirtuin family of protein deacetylases, and metabolic pathways, such as mitochondrial respiration and NAD+ biosynthesis. During the past two decades, mainly due to its considerable laboratory advantages (genetic plasticity, short life span, dened culture conditions, relative simplicity), budding yeast has positioned itself at the forefront of CR and longevity research.
