Pharmacological intervention in invertebrate aging

Lithgow, Gordon J.; Gill, Matthew S.; Olsen, Anders; Sampayo, James N.

doi:10.1007/s11357-005-3625-3

Cited by 19 publications

(31 citation statements)

References 89 publications

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“…The context-dependent effect of resveratrol on lifespan apparently is not a unique feature of resveratrol. Phytochemicals found in fruits and vegetables have been shown to be beneficial to health, promote healthy aging, and possibly longevity (Lithgow et al 2005;Obrenovich et al 2010). Emerging evidence indicates that prolongevity effects of phytochemicals depend on dietary conditions of the organism.…”

Section: Discussionmentioning

confidence: 99%

“…Other research on the potential for nutritional modulation of lifespan has suggested the possibility that polyphenolic compounds from fruits and vegetables added to diets modulates healthy aging and lifespan (Lithgow et al 2005;Obrenovich et al 2010). For example, resveratrol, a phytoallexin that is a member of the stilbene family, has been shown to extend lifespan in yeast, worms, flies, and a shortlived fish (Howitz et al 2003;Wood et al 2004;Valenzano et al 2006).…”

Section: Introductionmentioning

confidence: 99%

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The effect of resveratrol on lifespan depends on both gender and dietary nutrient composition in Drosophila melanogaster

Wang

Wheeler

Alberico

et al. 2011

AGE

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Resveratrol, a polyphenolic compound, has been shown to extend lifespan in different organisms. Emerging evidence suggests that the prolongevity effect of resveratrol depends on dietary composition. However, the mechanisms underlying the interaction of resveratrol and dietary nutrients in modulating lifespan remain elusive. Here, we investigated the effect of resveratrol on lifespan of Drosophila melanogaster fed diets differing in the concentrations of sugar, yeast extract, and palmitic acid representing carbohydrate, protein, and fat, respectively. Resveratrol at up to 200 μM in diets did not affect lifespan of wild-type female flies fed a standard, restricted or high sugar-low protein diet, but extended lifespan of females fed a low sugar-high protein diet. Resveratrol at 400 μM extended lifespan of females fed a high-fat diet. Lifespan extension by resveratrol was associated with downregulation of genes in aging-related pathways, including antioxidant peroxiredoxins, insulin-like peptides involved in insulin-like signaling and several downstream genes in Jun-kinase signaling involved in oxidative stress response. Furthermore, resveratrol increased lifespan of superoxide dismutase 1 (sod1) knockdown mutant females fed a standard or high-fat diet. No lifespan extension by resveratrol was observed in wild-type and sod1 knockdown males under the culture conditions in this study. Our results suggest that the gender-specific prolongevity effect of resveratrol is influenced by dietary composition and resveratrol promotes the survival of flies by modulating genetic pathways that can reduce cellular damage. This study reveals the context-dependent effect of resveratrol on lifespan and suggests the importance of dietary nutrients in implementation of effective aging interventions using dietary supplements.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The effect of resveratrol on lifespan depends on both gender and dietary nutrient composition in Drosophila melanogaster

Wang

Wheeler

Alberico

et al. 2011

AGE

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“…In addition, the characterization of drugs that extend lifespan can elucidate endogenous mechanisms involved in lifespan determination, because the targets of these drugs are likely to influence normal aging. The short lifespan and rapid aging of invertebrates make them powerful models for the identification of drugs that extend lifespan and for the characterization of the mechanism of action of these drugs (Lithgow et al ., 2005;Collins et al ., 2006;Olsen et al ., 2006a). The freeliving soil nematode Caenorhabditis elegans has been a leading system for studying genetic and pharmacologic influences on lifespan.…”

Section: Introductionmentioning

confidence: 99%

Valproic acid extends Caenorhabditis elegans lifespan

et al. 2008

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SummaryAging is an important biological phenomenon and a major contributor to human disease and disability, but no drugs have been demonstrated to delay human aging. Caenorhabditis elegans is a valuable model for studies of animal aging, and the analysis of drugs that extend the lifespan of this animal can elucidate mechanisms of aging and might lead to treatments for age-related disease. By testing drugs that are Food and Drug Administration approved for human use, we discovered that the mood stabilizer and anticonvulsant valproic acid (VA) extended C. elegans lifespan. VA also delayed age-related declines of body movement, indicating that VA delays aging. Valproic acid is a small carboxylic acid that is the most frequently prescribed anticonvulsant drug in humans. A structure-activity analysis demonstrated that the related compound valpromide also extends lifespan. Valproic acid treatment may modulate the insulin/IGF-1 growth factor signaling pathway, because VA promoted dauer larvae formation and DAF-16 nuclear localization. To investigate the mechanism of action of VA in delaying aging, we analyzed the effects of combining VA with other compounds that extend the lifespan of C. elegans . Combined treatment of animals with VA and the heterocyclic anticonvulsant trimethadione caused a lifespan extension that was significantly greater than treatment with either of these drugs alone. These data suggest that the mechanism of action of VA is distinct from that of trimethadione, and demonstrate that lifespan-extending drugs can be combined to produce additive effects.

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“…The resulting need to understand and alleviate age-related decline has led to pharmacological manipulation of age-related degeneration in several species like Saccharomyces cerevisiae (yeast), Drosophila melangoster (Fruit fly), Mus musculus (rodent) and (Nematode) Caenorhabditis elegans [11]. The nematode C. elegans, is a valuable model for studies of aging and age-related disorders [12] owing to its short 3-week life span, easy culture conditions and rapid generation time [13].…”

Section: Introductionmentioning

confidence: 99%

“…elegans is a multicellular eukaryote sharing its cellular, molecular and biochemical features with higher organisms. C. elegans is easy to maintain in the laboratory (in Petri dishes) and has a fast and convenient life cycle [11]. Embryogenesis occurs in about 12 hours, development to the adult stage occurs in 2.5 days, and the life span is 2-3 weeks.…”

Section: Introductionmentioning

confidence: 99%

Bioactive phytomolecules and aging in Caenorhabditis elegans

2015

Healthy Aging Res

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Aging is a complex phenomenon, a sum total of changes that occur in a living organism with the passage of time and leads to decreasing ability to survive stress, increasing functional impairment and growing probability of death. Aging changes can be attributed to development, genetic defects, environmental factors, disease and an innate process-the aging process. Aging has been one of the most crucial menace factors for a number of socioeconomic burdens, hence discovery of any new chemical that modulates aging in research model organisms could lead to a new strategy for working upon age related diseases like diabetes, cancer and neuro-degenerative disorders. The present review highlights the previous studies suggesting effective modulation of the life prolonging mechanistic pathways and lifespan by various phytomolecules. The free living nematode Caenorhabditis elegans is a well established multicellular model organism for aging in biological research, being used by different laboratories worldwide. The enormous characteristics of this animal model that has contributed to its success includes its genetic pliability, invariant and fully described developmental program, well characterized genome, ease of maintenance, short and fertile life cycle and small body size. Being a multicellular organism it goes through a complex developmental process, including embryogenesis, morphogenesis to grow into an adult so, any biological information from C. elegans may be directly linked with more complex organisms, such as human. The reports on life span extension on exposure to plant based compounds clearly depicts that aging can be slowed down and thus makes life span extension an interesting area for research. This review summarizes the current understanding on interaction of phytomolecules with signalling pathways of aging that provides potential application in human health improvement and development of antiaging therapeutics.

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Pharmacological intervention in invertebrate aging

Cited by 19 publications

References 89 publications

The effect of resveratrol on lifespan depends on both gender and dietary nutrient composition in Drosophila melanogaster

The effect of resveratrol on lifespan depends on both gender and dietary nutrient composition in Drosophila melanogaster

Valproic acid extends Caenorhabditis elegans lifespan

Bioactive phytomolecules and aging in Caenorhabditis elegans

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