title: Two neurons mediate diet-restriction-induced longevity in C. elegans.
abstract: Dietary restriction extends lifespan and retards age-related disease in many species and profoundly alters endocrine function in mammals. However, no causal role of any hormonal signal in diet-restricted longevity has been demonstrated. Here we show that increased longevity of diet-restricted Caenorhabditis elegans requires the transcription factor gene skn-1 acting in the ASIs, a pair of neurons in the head. Dietary restriction activates skn-1 in these two neurons, which signals peripheral tissues to increase metabolic activity. These findings demonstrate that increased lifespan in a diet-restricted metazoan depends on cell non-autonomous signalling from central neuronal cells to non-neuronal body tissues, and suggest that the ASI neurons mediate diet-restriction-induced longevity by an endocrine mechanism.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Bishop
authors.forename: Leonard
authors.initials: L
authors.lastname: Guarente
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000166:cytology* / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D031204:Caloric Restriction; D019069:Cell Respiration; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004032:Diet; D006257:Head; D008136:Longevity / Q000502:physiology*; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D010101:Oxygen Consumption; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C073702:skn-1 protein, C elegans