Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO

Wang, Yamei; Tissenbaum, Heidi A.

doi:10.1016/j.mad.2005.09.005

Cited by 238 publications

(177 citation statements)

References 49 publications

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“…Moreover, independent on the mechanisms that control the activity of sirtuins the evolutionary conservation of the regulated activity of sirtuins suggests that they represent a set of effector proteins in a signal transduction pathway important for survival that monitors cellular energy and redox states. This holds true also for the nematode Caenorhabditis elegans in which sir-2.1 deletion significantly suppressed the enhanced longevity of calorie-restricted mutants such as unc-13 and eat-2 (Wang and Tissenbaum, 2005). Moreover, a sir-2.1 deletion strain is short lived and stress sensitive (Wang and Tissenbaum, 2005) whereas increased dosage of sir-2.1 extends the adult life span of worms by up to 50% (Tissenbaum and Guarente, 2001).…”

Section: Molecular Links Of Cr and Aging Molecular Links Of Cr And Agmentioning

confidence: 83%

“…This holds true also for the nematode Caenorhabditis elegans in which sir-2.1 deletion significantly suppressed the enhanced longevity of calorie-restricted mutants such as unc-13 and eat-2 (Wang and Tissenbaum, 2005). Moreover, a sir-2.1 deletion strain is short lived and stress sensitive (Wang and Tissenbaum, 2005) whereas increased dosage of sir-2.1 extends the adult life span of worms by up to 50% (Tissenbaum and Guarente, 2001). The signaling pathways through which sirtuins transfer the metabolic alterations into effects on life span are currently under investigation.…”

Section: Molecular Links Of Cr and Aging Molecular Links Of Cr And Agmentioning

confidence: 83%

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Nutrition, sirtuins and aging

Wenzel

2006

Genes Nutr

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Section: Molecular Links Of Cr and Aging Molecular Links Of Cr And Agmentioning

confidence: 83%

Section: Molecular Links Of Cr and Aging Molecular Links Of Cr And Agmentioning

confidence: 83%

Nutrition, sirtuins and aging

Wenzel

2006

Genes Nutr

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“…2); however, the role of sirtuins in CR remains controversial. Deletion of C. elegans sir-2.1, combined with lesions in the eat-2 gene that genetically mimic CR, suppress the longevity of eat-2 mutant animals, indicating that sir-2.1 is required for CR-induced longevity (Wang and Tissenbaum, 2006). Consistent with these findings, a loss of function mutation in sir-2.1 prevents the induction of autophagy and the increase in longevity by caloric restriction, suggesting that CR induces autophagy in a sir-2.1-dependent manner.…”

Section: Sirtuinsmentioning

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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“…The Sir2 family members (sirtuins) play important roles in several CR model systems (Lin et al 2000;Rogina and Helfand 2004;Chen et al 2005;Nisoli et al 2005;Wang and Tissenbaum 2006). The use of NAD in the sirtuin-mediated deacetylation reactions provides a link between NAD metabolism and sirtuin-mediated metabolic regulations (Guarente 2006).…”

Section: Requirement Of Respiration and The Sir2 Family In Aat1 Mdh1mentioning

confidence: 99%

“…By coupling the cleavage of NAD and deacetylation of target proteins, Sir2 serves as a molecular link, relaying the cellular energy state to the machinery of life span regulation. The Sir2 family in higher eukaryotes also plays an important role in CR Chen et al 2005;Nisoli et al 2005;Wang and Tissenbaum 2006). In addition, the mammalian Sir2 family proteins (SIRT1-7) have been shown to regulate stress response, cell survival, as well as insulin and fat metabolism (Guarente 2006;Dilova et al 2007), suggesting a role for SIRT proteins in age-related metabolic diseases and perhaps human aging.…”

mentioning

confidence: 99%

The malate–aspartate NADH shuttle components are novel metabolic longevity regulators required for calorie restriction-mediated life span extension in yeast

Easlon¹,

Tsang²,

Skinner³

et al. 2008

Genes Dev.

138

118

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Recent studies suggest that increased mitochondrial metabolism and the concomitant decrease in NADH levels mediate calorie restriction (CR)-induced life span extension. The mitochondrial inner membrane is impermeable to NAD (nicotinamide adenine dinucleotide, oxidized form) and NADH, and it is unclear how CR relays increased mitochondrial metabolism to multiple cellular pathways that reside in spatially distinct compartments. Here we show that the mitochondrial components of the malate-aspartate NADH shuttle (Mdh1 [malate dehydrogenase] and Aat1 [aspartate amino transferase]) and the glycerol-3-phosphate shuttle (Gut2, glycerol-3-phosphate dehydrogenase) are novel longevity factors in the CR pathway in yeast. Overexpressing Mdh1, Aat1, and Gut2 extend life span and do not synergize with CR. Mdh1 and Aat1 overexpressions require both respiration and the Sir2 family to extend life span. The mdh1⌬aat1⌬ double mutation blocks CR-mediated life span extension and also prevents the characteristic decrease in the NADH levels in the cytosolic/nuclear pool, suggesting that the malate-aspartate shuttle plays a major role in the activation of the downstream targets of CR such as Sir2. Overexpression of the NADH shuttles may also extend life span by increasing the metabolic fitness of the cells. Together, these data suggest that CR may extend life span and ameliorate age-associated metabolic diseases by activating components of the NADH shuttles.[Keywords: Calorie restriction (CR); Sir2; aging; NADH shuttles; respiration; metabolism] Supplemental material is available at http://www.genesdev.org.

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Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO

Cited by 238 publications

References 49 publications

Nutrition, sirtuins and aging

Nutrition, sirtuins and aging

Autophagy and ageing: Insights from invertebrate model organisms

The malate–aspartate NADH shuttle components are novel metabolic longevity regulators required for calorie restriction-mediated life span extension in yeast

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