M Kaeberlein

..Dietary restriction (DR) increases life span and delays age-associated disease in many organisms. The mechanism by which DR enhances longevity is not well understood...

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..These shortcomings must be considered along with evidence supporting a role for Sir2 in CR in order to fully evaluate the validity of this model...

..We propose that the TOR and Sch9 kinases define a primary conduit through which excess nutrient intake limits longevity in yeast...

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..Contradictory to this, we find that CR greatly increases life span in cells lacking Sir2, Hst1, and Hst2, which suggests that CR is not mediated by Sir2, Hst2, or Hst1...

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..Here we briefly outline aging in yeast and describe recent findings that continue to keep this "simple" eukaryote at the forefront of aging research...

..This Hot Topic article discusses papers published in the last year related to the importance of translation and its regulation by signaling through the target of rapamycin kinase, in modulating aging and age-associated diseases...

..We propose that SSD1-V defines a previously undescribed pathway affecting cellular longevity and suggest that future studies on longevity-promoting genes should be carried out in long-lived SSD1-V strains...

..In this issue of Cell Metabolism, Li et al. (2008) provide evidence that SirT1 has properties consistent with both pro- and antiaging functions in mice...

..A meta-analysis of data derived from genome-wide studies of aging in simple eukaryotes will allow the identification of conserved determinants of longevity that can be tested in mammals...

..The first interventions to slow human ageing may spring from the humble yeast...

..Although the question of what causes aging still cannot be answered definitively, that day may be rapidly approaching...

..Compounds such as these, identified from longevity studies in model organisms, hold great promise as therapies to target multiple age-related diseases by modulating the molecular causes of aging...

..Importantly, studies published this year also began to provide insights into specific mechanisms by which altered mRNA translation does (and in some cases does not) slow aging in invertebrate model organisms...

..Thus, we propose that lifespan extension by CR is independent of sirtuins and that nicotinamide has sirtuin-independent effects on lifespan extension by CR...

..These findings indicate that Sir2 and calorie restriction act in parallel pathways to promote longevity in yeast and, perhaps, higher eukaryotes...

..In light of these findings, the mechanism accounting for putative longevity effects of resveratrol should be reexamined...

..Removal of bacterial food also increases lifespan when initiated in postreproductive adults, suggesting that dietary restriction started during middle age can result in a substantial longevity benefit that is independent of reproduction...

..In contrast to measurements of aging for mitotic cells, cell survival in the nonmitotic state is decreased by Sir2 activity under conditions that mimic calorie restriction...

..Together, these findings indicate that the genetic component of life span determination is significantly conserved between divergent eukaryotic species, and suggest pathways that are likely to play a similar role in mammalian aging...

..Genetic epistasis analyses suggest that dietary restriction, reduced 60S subunit abundance, and Gcn4 activation extend yeast life span by similar mechanisms...

..We also report that life-span extension from dietary restriction does not require any of the five yeast sirtuins (Sir2, Hst1, Hst2, Hst3, or Hst4) either alone or in combination...

..These results define a limited number of genes likely to regulate replicative life span in a strain-independent manner, and create a basis for future epistasis analysis to determine genetic pathways of aging...

..We propose that up-regulation of a highly conserved response to starvation-induced stress is important for life span extension by decreased TOR signaling in yeast and higher eukaryotes...

..Here we discuss the links between nutrient reduction and enhanced longevity with emphasis on evolutionarily conserved nutrient response signaling...

..Other significant findings have connected translation control with other known longevity pathways and provided fodder for mechanistic hypotheses. Here, we summarize advances in this emerging field and raise questions for future studies...

..remanei strains. Thus, we find no evidence that adaptation to laboratory conditions has significantly altered the aging process in C. elegans under either standard or food-restricted conditions...

..VHL-1 and HIF-1 control longevity by a mechanism distinct from both dietary restriction and insulin-like signaling. These findings define VHL-1 and the hypoxic response as an alternative longevity and protein homeostasis pathway...

..We conclude that acetic acid induced mortality is the primary mechanism of chronological aging in yeast under standard conditions...

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..These findings demonstrate that dietary restriction confers a general protective effect against proteotoxicity and promotes longevity by a mechanism involving hsf-1...

..Longevity studies in mammals are not published to date. Instead, we highlight studies in mouse models, which indicate that dampening the TOR pathway leads to widespread protection from an array of age-related diseases...

..This method has accuracy comparable to traditional assays, while allowing for higher throughput and decreased variability in measurement...

..Here we compare and contrast the results from genome-wide aging screens and assess the likelihood that there are "public" aging mechanisms...

..In summary, this study underscores and elaborates upon predicted pathways by which mutations restore mating function to yeast diploids and identifies new mutants warranting further study...

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..We propose that yeast deficient in peroxisomal and other functions are sensitive to oleate perhaps because of an inability to effectively control the fatty acid composition of membrane phospholipids...

..We also show that the histone deacetylase activity of Sir2p is necessary for the proper localiztion of the SIR complex to the telomeres...

..We discuss how this metabolic strategy may apply to CR in animals...

..This work also provides evidence that post-transcriptional regulation is likely to be important both for maintaining cell integrity and for promoting longevity...

..This metabolic shift likely increases NAD levels, thereby activating Sir2p and promoting longevity...

..Novel animal models, including those showing no evidence of aging, as well as ethical and political implications of embryonic stem cells and alternative medicine are also discussed...

..The use of this database by researchers who study aging should facilitate easy comparison of the genes and interventions that affect life span in different organisms...

..These studies will identify candidate therapeutic targets for several age-associated human diseases, including cancer, heart disease, diabetes, and Alzheimer's disease. ..

..These studies will identify candidate therapeutic targets for several age-associated human diseases, including cancer, heart disease, diabetes, and Alzheimer's disease. ..