Genes that may modulate longevity in C. elegans in both dauer larvae and long-lived daf-2 adults

Ruzanov, Peter; Riddle, Donald L; Marra, Marco A.; McKay, Sheldon; Jones, Steven J.M.

doi:10.1016/j.exger.2007.04.002

Cited by 29 publications

(36 citation statements)

References 68 publications

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“…Yeast mutants with increased lifespan had increased levels of TCA cycle metabolites [72]. A downregulation of TCA cycle and ETC gene expression occurs in long-lived C. elegans dauer larvae [19] while long-lived daf-2 insulin receptor mutants show either unchanged [19] or decreased [73] TCA cycle gene expression with either unchanged [19] or increased [73] ETC gene expression. Mutations in the Drosophila Indy gene [74], a sodium coupled TCA cycle dicarboxylate and tricarboxylate carrier in the plasma membrane extend lifespan.…”

Section: Discussionmentioning

confidence: 99%

Malate and Fumarate Extend Lifespan in Caenorhabditis elegans

et al. 2013

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Malate, the tricarboxylic acid (TCA) cycle metabolite, increased lifespan and thermotolerance in the nematode C. elegans. Malate can be synthesized from fumarate by the enzyme fumarase and further oxidized to oxaloacetate by malate dehydrogenase with the accompanying reduction of NAD. Addition of fumarate also extended lifespan, but succinate addition did not, although all three intermediates activated nuclear translocation of the cytoprotective DAF-16/FOXO transcription factor and protected from paraquat-induced oxidative stress. The glyoxylate shunt, an anabolic pathway linked to lifespan extension in C. elegans, reversibly converts isocitrate and acetyl-CoA to succinate, malate, and CoA. The increased longevity provided by malate addition did not occur in fumarase (fum-1), glyoxylate shunt (gei-7), succinate dehydrogenase flavoprotein (sdha-2), or soluble fumarate reductase F48E8.3 RNAi knockdown worms. Therefore, to increase lifespan, malate must be first converted to fumarate, then fumarate must be reduced to succinate by soluble fumarate reductase and the mitochondrial electron transport chain complex II. Reduction of fumarate to succinate is coupled with the oxidation of FADH2 to FAD. Lifespan extension induced by malate depended upon the longevity regulators DAF-16 and SIR-2.1. Malate supplementation did not extend the lifespan of long-lived eat-2 mutant worms, a model of dietary restriction. Malate and fumarate addition increased oxygen consumption, but decreased ATP levels and mitochondrial membrane potential suggesting a mild uncoupling of oxidative phosphorylation. Malate also increased NADPH, NAD, and the NAD/NADH ratio. Fumarate reduction, glyoxylate shunt activity, and mild mitochondrial uncoupling likely contribute to the lifespan extension induced by malate and fumarate by increasing the amount of oxidized NAD and FAD cofactors.

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Section: Discussionmentioning

confidence: 99%

Malate and Fumarate Extend Lifespan in Caenorhabditis elegans

et al. 2013

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“…These processes certainly involve widespread and coordinated regulation of gene expression, on the transcriptional and post-transcriptional levels. Changes in gene transcript levels have been documented that accompany the increased stress resistance, reduced metabolism, and lengthened life span characteristic of dauer larvae (Dalley and Golomb 1992;Jones et al 2001;Holt and Riddle 2003;Wang and Kim 2003;Ruzanov et al 2007;Jeong et al 2009b;Ruzanov and Riddle 2010). Similarly, transcriptional changes have been described associated with L1 diapause (Baugh et al 2009).…”

Section: Discussionmentioning

confidence: 99%

“…The majority of previously published studies have compared mRNA levels or protein levels in dauer larvae to non-dauer animals of various developmental stages (Dalley and Golomb 1992;Jones et al 2001;Holt and Riddle 2003;Wang and Kim 2003;Ruzanov et al 2007;Jeong et al 2009b;Ruzanov and Riddle 2010). An additional study monitored gene expression changes during entry to dauer (Jeong et al 2009a).…”

Section: Introductionmentioning

confidence: 99%

Effect of life history on microRNA expression during C. elegans development

Karp¹,

Hammell²,

Ow³

et al. 2011

RNA

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Animals have evolved mechanisms to ensure the robustness of developmental outcomes to changing environments. MicroRNA expression may contribute to developmental robustness because microRNAs are key post-transcriptional regulators of developmental gene expression and can affect the expression of multiple target genes. Caenorhabditis elegans provides an excellent model to study developmental responses to environmental conditions. In favorable environments, C. elegans larvae develop rapidly and continuously through four larval stages. In contrast, in unfavorable conditions, larval development may be interrupted at either of two diapause stages: The L1 diapause occurs when embryos hatch in the absence of food, and the dauer diapause occurs after the second larval stage in response to environmental stimuli encountered during the first two larval stages. Dauer larvae are stress resistant and long lived, permitting survival in harsh conditions. When environmental conditions improve, dauer larvae re-enter development, and progress through two post-dauer larval stages to adulthood. Strikingly, all of these life history options (whether continuous or interrupted) involve an identical pattern and sequence of cell division and cell fates. To identify microRNAs with potential functions in buffering development in the context of C. elegans life history options, we used multiplex real-time PCR to assess the expression of 107 microRNAs throughout development in both continuous and interrupted life histories. We identified 17 microRNAs whose developmental profile of expression is affected by dauer life history and/or L1 diapause, compared to continuous development. Hence these microRNAs could function to regulate gene expression programs appropriate for different life history options in the developing worm.

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“…Long lived yeast mitochondrial mutants activate a retrograde signaling pathway that results in the activation of specific transcription factors that will shift metabolism away from the Krebs cycle towards the glyoxylate cycle. This metabolic shift has also been observed in dauer larvae and long-lived daf-2 mutants [55,56]. It is possible that a metabolic shift also contributes to the extended lifespan of certain PHB-depleted C. elegans mutants.…”

Section: Introductionmentioning

confidence: 67%

Opposing function of mitochondrial prohibitin in aging

Artal‐Sanz

Tavernarakis

2010

Aging

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While specific signalling cascades involved in aging, such as the insulin/IGF-1 pathway, are well-described, the actual metabolic changes they elicit to prolong lifespan remain obscure. Nevertheless, the tuning of cellular metabolism towards maximal survival is the molecular basis of longevity. The eukaryotic mitochondrial prohibitin complex is a macromolecular structure at the inner mitochondrial membrane, implicated in several important cellular processes such as mitochondrial biogenesis and function, molecular signalling, replicative senescence, and cell death. Recent studies in C. elegans have revealed that prohibitin differentially influences aging by moderating fat metabolism and energy production, in response to both intrinsic signalling events and extrinsic cues. These findings indicate that prohibitin is a context-dependent modulator of longevity. The tight evolutionary conservation and ubiquitous expression of prohibitin proteins suggest a similar role for the mitochondrial prohibitin complex during aging in other organisms.

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Genes that may modulate longevity in C. elegans in both dauer larvae and long-lived daf-2 adults

Cited by 29 publications

References 68 publications

Malate and Fumarate Extend Lifespan in Caenorhabditis elegans

Malate and Fumarate Extend Lifespan in Caenorhabditis elegans

Effect of life history on microRNA expression during C. elegans development

Opposing function of mitochondrial prohibitin in aging

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