Valproic acid extends Caenorhabditis elegans lifespan.

Department of Developmental Biology, Washington University School of Medicine, 660 South Euclid Ave., Campus Box 8103, St. Louis, MO 63110, USA.
Aging cell (Impact Factor: 5.94). 07/2008; 7(3):305-17. DOI: 10.1111/j.1474-9726.2008.00375.x
Source: PubMed

ABSTRACT Aging 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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Screening small molecules having anti-aging effect and researching the mechanism are of great practical significance for discovering new effective targets for treatment of age-related diseases and tumors, developing new drugs and promoting human health. What is more important is that these small molecules can be used as breakthrough points for the specific molecular mechanisms of aging, cancer and other biological phenomena via in-depth study. And this has an important role in promoting the development of molecular biology and other related life sciences. This article summarizes some representative anti-aging small molecules of the past decade or two and focuses on their molecular mechanisms.
    Progress in Biochemistry and Biophysics 09/2010; 37(9):932-938. DOI:10.3724/SP.J.1206.2010.00152 · 0.29 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fullerene derivatives have attracted extensive attention in biomedical fields and polyhydroxyl fullerene (fullerenol), a water-soluble fullerene derivative, is demonstrated as a powerful antioxidant. To further assess their anti-aging and anti-stress potential, we employed Caenorhabditis elegans (C. elegans) as a model organism to evaluate the effects of fullerenol on the growth, development, behavior and anti-stress ability in vivo. The data show that fullerenol has no obviously toxic effect on nematodes and can delay C. elegans aging progress under normal condition. Further studies demonstrate that fullerenol attenuates endogenous levels of reactive oxygen species and provides protection to C. elegans under stress conditions by up-regulating stress-related genes in a DAF-16 depend manner and improving lifespan. In summary, our data suggest that fullerenol might be a safe and reasonable anti-aging candidate with great potential in vivo.
    Biomaterials 02/2015; 42. DOI:10.1016/j.biomaterials.2014.11.048 · 8.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Royal jelly (RJ) produced by honeybees has been reported to possess diverse health-beneficial properties and has been implicated to have a function in longevity across diverse species as well as honeybees. 10-Hydroxy-2-decenoic acid (10-HDA), the major lipid component of RJ produced by honeybees, was previously shown to increase the lifespan of Caenorhabditis elegans. The objective of this study is to elucidate signaling pathways that are involved in the lifespan extension by 10-HDA. 10-HDA further extended the lifespan of the daf-2 mutants, which exhibit long lifespan through reducing insulin-like signaling (ILS), indicating that 10-HDA extended lifespan independently of ILS. On the other hand, 10-HDA did not extend the lifespan of the eat-2 mutants, which show long lifespan through dietary restriction caused by a food-intake defect. This finding indicates that 10-HDA extends lifespan through dietary restriction signaling. We further found that 10-HDA did not extend the lifespan of the long-lived mutants in daf-15, which encodes Raptor, a target of rapamycin (TOR) components, indicating that 10-HDA shared some longevity control mechanisms with TOR signaling. Additionally, 10-HDA was found to confer tolerance against thermal and oxidative stress. 10-HDA increases longevity not through ILS but through dietary restriction and TOR signaling in C. elegans.
    Journal of aging research 02/2015; 2015:1-7. DOI:10.1155/2015/425261

Full-text (2 Sources)

1 Download
Available from
Feb 18, 2015