Influence of TOR kinase on lifespan in C. elegans

Vellai, Tibor; Takács‐Vellai, Krisztina; Zhang, Yue; Kovács, Attila; Orosz, László; Müller, Fritz

doi:10.1038/426620a

Cited by 1,025 publications

(766 citation statements)

References 9 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%

“…In C. elegans, downregulation of the activity of CeTOR/let-363 or the TOR accessory protein raptor, DAF-15, extends adult lifespan (Vellai et al, 2003;Jia et al, 2004). Worms bearing mutations in S6K (RSKS-1) and components of the translational machinery such as ribosomal proteins and translation initiation factors, live longer (Hansen et al, 2007;Kaeberlein and Kennedy, 2008;Syntichaki et al, 2007).…”

Section: Tor Signallingmentioning

confidence: 99%

“…As mentioned above, TOR, similarly to insulin/IGF-1 signalling acts during adulthood to influence ageing. However, the long-lived phenotype of let-363 RNAi worms is not suppressed by mutations in daf-16, indicating that TOR may be acting downstream or independently of DAF-16 (Jia et al, 2004;Vellai et al, 2003). Importantly, knockout of ife-2, one of five C. elegans eIF4E isoforms (ife-1 to ife-5), extends lifespan, and enhances resistance to oxidative stress, UV irradiation and heat shock independently of DAF-16/FoxO (Syntichaki et al, 2007).…”

Section: Tor Signallingmentioning

confidence: 99%

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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%

Section: Tor Signallingmentioning

confidence: 99%

Section: Tor Signallingmentioning

confidence: 99%

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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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“…Upon ligand binding, the insulin/IGF‐1 plasma membrane receptor DAF‐2 (constitutive dauer formation) activates a cascade of downstream cytoplasmic kinases, which eventually inhibits the FOXO‐like transcription factor DAF‐16 (Ogg et al., 1997; Figure 1B). When IIS is lowered, DAF‐16 effectively translocates into the nucleus to dictate the expression of target genes required for lifespan extension, stress resistance, and dauer larval formation (dauer is an alternative, nonaging developmental diapause triggered by starvation, crowding, and high temperatures in the wild‐type; Fielenbach & Antebi, 2008; Vellai et al., 2003). We found that in long‐lived daf‐2(‐) loss‐of‐function mutant strains maintained at temperatures permitting reproductive growth, hermaphrodites also tend to live longer than males (Figure 1c,c' and Figure S3).…”

Section: Resultsmentioning

confidence: 99%

Sex‐specific regulation of aging in Caenorhabditis elegans

et al. 2018

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SummaryA fascinating aspect of sexual dimorphism in various animal species is that the two sexes differ substantially in lifespan. In humans, for example, women's life expectancy exceeds that of men by 3–7 years. Whether this trait can be attributed to dissimilar lifestyles or genetic (regulatory) factors remains to be elucidated. Herein, we demonstrate that in the nematode Caenorhabditis elegans, the significantly longer lifespan of hermaphrodites—which are essentially females capable of sperm production—over males is established by TRA‐1, the terminal effector of the sex‐determination pathway. This transcription factor directly controls the expression of daf‐16/FOXO, which functions as a major target of insulin/IGF‐1 signaling (IIS) and key modulator of aging across diverse animal phyla. TRA‐1 extends hermaphrodite lifespan through promoting daf‐16 activity. Furthermore, TRA‐1 also influences reproductive growth in a DAF‐16‐dependent manner. Thus, the sex‐determination machinery is an important regulator of IIS in this organism. These findings provide a mechanistic insight into how longevity and development are specified unequally in the two genders. As TRA‐1 is orthologous to mammalian GLI (glioma‐associated) proteins, a similar sex‐specific mechanism may also operate in humans to determine lifespan.

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Influence of TOR kinase on lifespan in C. elegans

Cited by 1,025 publications

References 9 publications

Autophagy and ageing: Insights from invertebrate model organisms

Autophagy and ageing: Insights from invertebrate model organisms

Stress and mTORture signaling

Sex‐specific regulation of aging in Caenorhabditis elegans

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