title: Anticonvulsant medications extend worm life-span.
abstract: Genetic studies have elucidated mechanisms that regulate aging, but there has been little progress in identifying drugs that delay aging. Here, we report that ethosuximide, trimethadione, and 3,3-diethyl-2-pyrrolidinone increase mean and maximum life-span of Caenorhabditis elegans and delay age-related declines of physiological processes, indicating that these compounds retard the aging process. These compounds, two of which are approved for human use, are anticonvulsants that modulate neural activity. These compounds also regulated neuromuscular activity in nematodes. These findings suggest that the life-span-extending activity of these compounds is related to the anticonvulsant activity and implicate neural activity in the regulation of aging.
authors.affiliation: Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Evason
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.forename: Idella
authors.initials: I
authors.lastname: Yamben
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Covey
authors.forename: Kerry
authors.initials: K
authors.lastname: Kornfeld
mesh_terms: D000375:Aging / Q000187:drug effects*; D000448:Aldicarb / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology; D012734:Disorders of Sex Development; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004832:Epilepsy, Absence / Q000188:drug therapy; D005013:Ethosuximide / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D051858:Forkhead Transcription Factors; D017238:Genes, Helminth; D006801:Humans; D007769:Lactams / Q000494:pharmacology*; D008136:Longevity / Q000187:drug effects*; D009068:Movement / Q000187:drug effects; D009132:Muscles / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D009154:Mutation; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010058:Oviposition / Q000187:drug effects; D010614:Pharynx / Q000187:drug effects / Q000502:physiology; D012098:Reproduction / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D014293:Trimethadione / Q000494:pharmacology* / Q000627:therapeutic use; D014844:Vulva
chemical_list: C113196:3,3-diethyl-2-pyrrolidinone; D000927:Anticonvulsants; D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D007769:Lactams; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D005013:Ethosuximide; D000448:Aldicarb; D014293:Trimethadione