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.
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In C. elegans, the ASI neurons-two specific neurons-could mediate lifespan extension from caloric restriction.
“A notable example of the central regulatory function of the nervous system was the finding that two neurons in C. elegans, the ASI neurons, could mediate lifespan extension in response to caloric restriction (92).”
From Neural mechanisms of ageing and cognitive decline (2010) · cites this paper as [92]
The lifespan increase depended on SKN-1 activity specifically in ASI neurons; SKN-1 is a transcription factor homologous to mammalian NFE2L2 and is known to activate defences against oxidative and xenobiotic stress.
“Lifespan extension required ASI-neuron-specific activity of the transcription factor SKN-1, a homologue of the mammalian NF-E2 related factor (NFE2L2), with known functions in activating cellular defences against oxidative and xenobiotic stress.”
From Neural mechanisms of ageing and cognitive decline (2010) · cites this paper as [92]
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- Authors
- Bishop, N. A., & Guarente, L.
- Affiliations
- Massachusetts Institute of Technology (US)
- Corresponding author
- Guarente, Leonard
- ORCID
- Guarente, Leonard
- Venue
- Nature
- Published
- 2007-05
- Volume
- 447
- Issue
- 7144
- Pages
- 545-549
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2004923406
- Cited by
- 643
- References
- 40
- Citations by year
- 2026: 15 · 2025: 15 · 2024: 19 · 2023: 25 · 2022: 21 · 2021: 32 · 2020: 25 · 2019: 21 · 2018: 29 · 2017: 34 · 2016: 42 · 2015: 42 · 2014: 42 · 2013: 49 · 2012: 39
- FWCI
- 14.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Keywords
- dietary restriction, longevity, Caenorhabditis elegans, SKN-1, PHA-4, FoxA transcription factor, hormone signaling, metabolic activity, aging, caloric restriction
- MeSH terms
- Animals, Diet, DNA-Binding Proteins, Head, Longevity, Models, Biological, Neurons, Oxygen Consumption, Transcription Factors, Caenorhabditis elegans, Cell Respiration, Caenorhabditis elegans Proteins, Caloric Restriction
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