1. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

Correspondence to: Leonard Guarente¹ Correspondence and requests for materials should be addressed to L.G. (Email: leng@mit.edu).

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.

1. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

Correspondence to: Leonard Guarente¹ Correspondence and requests for materials should be addressed to L.G. (Email: leng@mit.edu).

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