Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients

Kaeberlein, Matt; Powers, Ryan; Steffen, Kristan K.; Westman, Eric A.; Hu, Di; Dang, Nick; Kerr, Emily O.; Kirkland, Kathryn T.; Fields, Stanley; Kennedy, Brian K.

doi:10.1126/science.1115535

Cited by 1,199 publications

(1,207 citation statements)

References 24 publications

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“…Attenuation of TOR function in yeast, worms and flies results in a significant increase of lifespan (Kaeberlein et al, 2005;Kapahi et al, 2004;Martin and Hall, 2005;Vellai et al, 2003). TOR signalling controls various growth-related processes, including protein synthesis and autophagy, both of which are implicated in the modulation of lifespan.…”

Section: Tor Signallingmentioning

confidence: 99%

Autophagy and ageing: Insights from invertebrate model organisms

Lionaki

Markaki

Tavernarakis

2013

Ageing Research Reviews

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a b s t r a c tAgeing in diverse species ranging from yeast to humans is associated with the gradual, lifelong accumulation of molecular and cellular damage. Autophagy, a conserved lysosomal, self-destructive process involved in protein and organelle degradation, plays an essential role in both cellular and whole-animal homeostasis. Accumulating evidence now indicates that autophagic degradation declines with age and this gradual reduction of autophagy might have a causative role in the functional deterioration of biological systems during ageing. Indeed, loss of autophagy gene function significantly influences longevity. Moreover, genetic or pharmacological manipulations that extend lifespan in model organisms often activate autophagy. Interestingly, conserved signalling pathways and environmental factors that regulate ageing, such as the insulin/IGF-1 signalling pathway and oxidative stress response pathways converge on autophagy. In this article, we survey recent findings in invertebrates that contribute to advance our understanding of the molecular links between autophagy and the regulation of ageing. In addition, we consider related mechanisms in other organisms and discuss their similarities and idiosyncratic features in a comparative manner.

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Section: Tor Signallingmentioning

confidence: 99%

Autophagy and ageing: Insights from invertebrate model organisms

Lionaki

Markaki

Tavernarakis

2013

Ageing Research Reviews

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“…In recent years, numerous stimuli have been shown to cause changes in the activity of the TOR/IIS cascades. Studies in yeast and higher eukaryotes have shown that lowered TOR (and/or decreased IIS in higher eukaryotes) signaling pathway activity increases lifespan (Kenyon et al, 1993;Guarente and Kenyon, 2000;Vellai et al, 2003;Hwangbo et al, 2004;Kapahi et al, 2004;Kaeberlein et al, 2005;Powers et al, 2006). In addition, decreased IIS/TOR signaling activity is associated with increased resistance to some types of stress, suggesting that this pathway plays also an important role in the adaption to different stress conditions (Scott et al, 2002;Holzenberger et al, 2003;Broughton et al, 2005;Teleman et al, 2005;Tettweiler et al, 2005;Powers et al, 2006).…”

Section: Stress and Mtormentioning

confidence: 99%

Stress and mTORture signaling

2006

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“…Although free radicals have been correlated with senescence, in both mice and worms, there is increasing evidence that they may not be the causative agent (Doonan et al 2008;Ran et al 2007;Van Raamsdonk and Hekimi 2009;Van Remmen et al 2003;Yen et al 2009). The target of rapamycin pathway, which may also link DR and insulin/IGF signaling, regulates autophagy, and this is important for both DR and insulin/IGF mediated longevity (Hansen et al 2008;Kaeberlein et al 2005;Kapahi et al 2004;Melendez et al 2003).…”

Section: Gompertz Analysismentioning

confidence: 99%

Evidence for only two independent pathways for decreasing senescence in Caenorhabditis elegans

Yen

Mobbs

2009

AGE

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Cold temperature, dietary restriction, reduced insulin/insulin-like growth factor signaling, and mutations in mitochondrial genes have all been shown to extend the lifespan of Caenorhabditis elegans (Kenyon et al., Nature 366:461-464, 1993; Klass, Mech Ageing Dev 6:413-429, 1977; Lakowski and Hekimi, Science 272:1010-1013. Additionally, all of them extend the lifespan of mice (Bluher et al., Science 299:572-574, 2003; Conti et al., Science 314:825-828, 2006; Holzenberger et al., Nature 421:182-187, 2003; Liu et al., Genes Dev 19:2424-2434 Weindruch and Walford, Science 215:1415-1418, 1982. The mechanism by which these treatments extend lifespan is currently unknown, but our study uses an epistatic approach to show that these four manipulations are mainly additive in terms of lifespan. Classical interpretation of this data suggests that these manipulations are independent of each other. However, using a Gompertz mortality rate analysis, the maximum mortality rate doubling time can be achieved through the use of only dietary restriction and cold temperature, suggesting that the mechanisms by which cold temperature and caloric restriction extend lifespan are the only independent mechanisms.

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Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients

Cited by 1,199 publications

References 24 publications

Autophagy and ageing: Insights from invertebrate model organisms

Autophagy and ageing: Insights from invertebrate model organisms

Stress and mTORture signaling

Evidence for only two independent pathways for decreasing senescence in Caenorhabditis elegans

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