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Abstract

This annual review focuses on invertebrate model organisms, which continue to yield fundamental new insights into mechanisms of aging. This year, the budding yeast has been used to understand how asymmetrical partitioning of cellular constituents at cell division can produce a rejuvenated offspring from an aging parent. Blocking of sensation of carbon dioxide is shown to extend fly lifespan and to mediate the lifespan-shortening effect of sensory exposure to fermenting yeast. A new study of daf-16, the key forkhead transcription factor that mediates extension of lifespan by mutants in the insulin-signalling pathway in Caenorhabditis elegans, demonstrates that expression of tissue-specific isoforms with different patterns of response to upstream signalling mediates the highly pleiotropic effects of the pathway on lifespan and other traits. A new approach to manipulating mitochondrial activity in Drosophila, by introducing the yeast NADH-ubiquinone oxidoreductase, shows promise for understanding the role of mitochondrial reactive oxygen species in aging. An exciting new study of yeast and mammalian cells implicates deterioration of the nuclear pore, and consequent leakage of cytoplasmic components into the nucleus, as an important cause of aging in postmitotic tissues. Loss of, or damage to, chromosome-associated histones is also implicated in the determination of lifespan in yeast, worms and fruit flies. The relationship between functional aging, susceptibility to aging-related disease and lifespan itself are explored in two studies in C. elegans, the first examining the role of dietary restriction and reduced insulin signalling in cognitive decline and the second profiling aggregation of the proteome during aging. The invertebrates continue to be a power house of discovery for future work in mammals.