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Two neurons mediate diet-restriction-induced longevity in C. elegans


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.

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Figure 1: Lifespan extension by dietary restriction.
Figure 2: skn-1 functions in the ASI neurons to mediate dietary restriction longevity.
Figure 3: The ASI neurons are necessary for dietary restriction longevity.
Figure 4: Dietary restriction activates skn-1 in the ASI neurons and increases whole-body respiration.
Figure 5: Model of skn-1 function during dietary restriction.


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We thank H. R. Horvitz for allowing use of essential equipment, and members of the Guarente and Horvitz laboratories for advice and discussions. We thank D. Kim and F. Ausubel for the gift of an unpublished strain. Many of the strains used in this work were provided by the Caenorhabditis Genetics Center. This work was supported by a grant from the National Institutes of Health.

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Correspondence to Leonard Guarente.

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L.G. is a founder of Elixir Pharmaceuticals.

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This file contains Supplementary Figures S1 – S7, Supplementary Tables S1 – S2 and additional references. (PDF 2104 kb)

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Bishop, N., Guarente, L. Two neurons mediate diet-restriction-induced longevity in C. elegans. Nature 447, 545–549 (2007).

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