Pharmacology of delayed aging and extended lifespan of Caenorhabditis elegans.
The identification and analysis of compounds that delay aging and extend lifespan is an important aspect of gerontology research; these studies can test theories of aging, lead to the discovery of endogenous systems that influence aging, and establish the foundation for treatments that might delay normal human aging. Here we review studies using the nematode Caenorhabditis elegans to identify and characterize compounds that delay aging and extend lifespan. These studies are considered in four groups: (1) Studies that address the free-radical theory of aging by analyzing candidate compounds with antioxidant activities including vitamin E, tocotrienols, coenzyme Q, and Eukarion-8/134. (2) Studies that analyze plant extracts (blueberry and Ginko biloba) that contain a mixture of compounds. (3) Studies of resveratrol, which was identified in a screen for compounds that affect the activity of the Sir2 protein that influences lifespan. (4) Studies based on screening compound libraries using C. elegans aging as a bioassay, which led to the identification of the anticonvulsant medicines ethosuximide and trimethadione. There has been exciting progress in the analysis of compounds that influence C. elegans aging, and important challenges and opportunities remain in determining the mechanisms of action of these compounds and the relevance of these observations to aging of other animals.
Collins
James J
JJ
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Evason
Kimberley
K
Kornfeld
Kerry
K
D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D029798:Blueberry Plants; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000502:physiology; D005013:Ethosuximide / Q000494:pharmacology; D005029:Ethylenediamines / Q000494:pharmacology; D020441:Ginkgo biloba; D008136:Longevity / Q000187:drug effects / Q000502:physiology; D009942:Organometallic Compounds / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D000077185:Resveratrol; D012459:Salicylates / Q000494:pharmacology; D013267:Stilbenes / Q000494:pharmacology; D024508:Tocotrienols / Q000494:pharmacology; D014293:Trimethadione / Q000494:pharmacology; D014451:Ubiquinone / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D000927:Anticonvulsants; D000975:Antioxidants; C433928:EUK-134; D005029:Ethylenediamines; D009942:Organometallic Compounds; D010936:Plant Extracts; D012459:Salicylates; D013267:Stilbenes; D024508:Tocotrienols; D014451:Ubiquinone; D014810:Vitamin E; C090577:N,N'-bis(salicylideneamino)ethane-manganese(II); D005013:Ethosuximide; D000077185:Resveratrol; D014293:Trimethadione