<i>Caenorhabditis elegans</i> Life Span Studies: The Challenge of Maintaining Synchronous Cohorts

Gruber, Jan; Poovathingal, Suresh; Schaffer, Sebastian; Ng, Li Fang; Halliwell, Barry

doi:10.1089/rej.2009.0943

Cited by 3 publications

(3 citation statements)

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“…Although evolutionarily far from mammals, the nematode Caenorhabditis elegans (C. elegans) has proven to be an invaluable tool for studying basic mechanisms of, and interventions into, aging (Gems and Partridge 2001;Gruber et al 2009Gruber et al , 2010Kenyon 2010;Kimura et al 1997;Olsen et al 2006). For example, the IGF signaling pathway, first discovered in C. elegans, is highly conserved (Gems and Partridge 2001;Kenyon 2010;Kimura et al 1997).…”

Section: Introductionmentioning

confidence: 99%

The effect of dichloroacetate on health- and lifespan in C. elegans

Schaffer

Gruber

et al. 2010

Biogerontology

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Aging is associated with increased vulnerability to chronic, degenerative diseases and death. Strategies for promoting healthspan without necessarily affecting lifespan or aging rate have gained much interest. The mitochondrial free radical theory of aging suggests that mitochondria and, in particular, age-dependent mitochondrial decline play a central role in aging, making compounds that affect mitochondrial function a possible strategy for the modulation of healthspan and possibly the aging rate. Here we tested such a "metabolic tuning" approach in nematodes using the mitochondrial modulator dichloroacetate (DCA). We explored DCA as a proof-of-principle compound to alter mitochondrial parameters in wild-type animals and tested whether this approach is suitable for reducing reactive oxygen species (ROS) production and for improving organismal health- and lifespan. In parallel, we addressed the potential problem of operator bias by running both unblinded and blinded lifespan studies. We found that DCA treatment (1) increased ATP levels without elevating oxidative protein damage and (2) reduced ROS production in adult C. elegans. DCA treatment also significantly prolonged nematode health- and lifespan, but did not strongly impact mortality doubling time. Operator blinding resulted in considerably smaller lifespan-extending effects of DCA. Our data illustrate the promise of a "metabolic tuning" intervention strategy, emphasize the importance of mitochondria in nematode aging and highlight operator bias as a potential confounder in lifespan studies.

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Section: Introductionmentioning

confidence: 99%

The effect of dichloroacetate on health- and lifespan in C. elegans

Schaffer

Gruber

et al. 2010

Biogerontology

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“…While this might seem low, it could result in 10% of the aging cohort actually being from the next generation. Since maximum lifespan is often determined as the mean of the longest living 10% of the cohort, this could cause significant artifact [136].…”

Section: Generating and Maintaining Synchronized Culturesmentioning

confidence: 99%

Deceptively simple but simply deceptive – Caenorhabditis elegans lifespan studies: Considerations for aging and antioxidant effects

et al. 2009

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Edited by Vladimir SkulachevKeywords: Aging Reactive oxygen species Antioxidant Lifespan Artifact Caenorhabditis elegans a b s t r a c tThe nematode worm Caenorhabditis elegans (C. elegans) is increasingly popular as a model organism for aging studies as well as for testing antioxidants and other compounds for effects on longevity. However, results in the literature are sometimes confusing and contradictory [1][2][3][4]. This review introduces C. elegans as a model organism, discusses aspects that make it attractive for aging and antioxidant research, and addresses some problems and potential artifacts.

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“…2,3 Such studies, which require age-synchronized worms are, however, significantly complicated by the worm's biology: it grows and reproduces so quickly that successive generations of offspring become mixed up with adults in a matter of days. 4 Several methods for isolating the large number of adults needed for transcriptomic, proteomic and metabolomic studies have been used: manual picking, genetic or chemical sterilization, 5 and mechanical sorting using a FACS-based device, the COPAS Biosorter (Union Biometrica, Holliston, MA). 6 Each of these approaches has major drawbacks: manual picking is tedious, sterilization perturbs the animal's biology and the Biosorter is both complex and expensive.…”

mentioning

confidence: 99%