Genetic Analysis of Tissue Aging in Caenorhabditis elegans : A Role for Heat-Shock Factor and Bacterial Proliferation
Abstract
The genetic analysis of life span has revealed many interesting genes and pathways; however, our understanding of aging has been limited by the lack of a way to assay the aging process itself. Here we show that the tissues of aging worms have a characteristic appearance that is easy to recognize and quantify using Nomarski optics. We have used this assay to determine whether life-span mutations affect the rate of aging, to identify animals that age more rapidly than normal, and to infer the cause of death in C. elegans. Mutations that reduce insulin/IGF-1 signaling double the life span of C. elegans, and we find that tissue decline is slowed in these mutants. Thus this endocrine system appears to influence the rate at which tissues age. This effect extends even to the germline, which is the only mitotically active tissue in the adult. We find that Nomarski microscopy also allows a ready distinction between short-lived mutants that age more rapidly than normal and those that are simply sick, and we have identified an RNAi clone that confers a dramatic rapid-aging phenotype. This clone encodes the C. elegans heat-shock factor (HSF), a transcription factor that regulates the response to heat and oxidative stress. This suggests that heat-shock proteins, many of which act as chaperones, may function in normal animals to slow the rate of aging. Finally, we have identified a cause of death of C. elegans: namely, proliferating bacteria. This suggests that increased susceptibility to bacterial infections contributes to mortality in these animals, just as it does in humans.
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C. elegans life span is not regulated by a canonical caspase-dependent PCD.
“Mutation of ced-3 was reported not to affect adult life span, suggesting that C. elegans life span is not regulated by a canonical caspase-dependent PCD(Garigan et al., 2002), however a possible role for caspase-independent PCD or necrosis pathways in regulating C. elegans life span cannot yet be ruled out.”
From Programmed cell death in aging (2015) · cites this paper as Garigan et al., 2002
Mutation of ced-3 was reported not to affect adult life span.
“Mutation of ced-3 was reported not to affect adult life span, suggesting that C. elegans life span is not regulated by a canonical caspase-dependent PCD(Garigan et al., 2002), however a possible role for caspase-independent PCD or necrosis pathways in regulating C. elegans life span cannot yet be ruled out.”
From Programmed cell death in aging (2015) · cites this paper as Garigan et al., 2002
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- Authors
- Garigan, D., Hsu, A.-L., Fraser, A. G., Kamath, R. S., Ahringer, J., & Kenyon, C.
- Affiliations
- University of California, San Francisco (US)
- University of Cambridge (GB)
- Corresponding author
- Kenyon, Cynthia
- Venue
- Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-07-01
- Volume
- 161
- Issue
- 3
- Pages
- 1101-1112
- ISSN
- 0016-6731 (ISSN-L)
- 1943-2631
- OpenAlex
- W2151034892
- Cited by
- 803
- References
- 45
- Citations by year
- 2026: 18 · 2025: 27 · 2024: 35 · 2023: 36 · 2022: 39 · 2021: 28 · 2020: 35 · 2019: 36 · 2018: 30 · 2017: 34 · 2016: 39 · 2015: 29 · 2014: 37 · 2013: 27 · 2012: 43
- FWCI
- 7.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (054523/Z/98/C)
- 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 › Telomeres, Telomerase, and Senescence
- Keywords
- tissue aging, Caenorhabditis elegans, heat shock transcription factor, heat shock proteins, bacterial growth, bacterial infection, insulin/IGF-1 signaling, lifespan, aging rate, mortality, molecular chaperones
- MeSH terms
- Aging, Animals, Female, Genotype, Germ Cells, Heat-Shock Proteins, Insulin, Insulin-Like Growth Factor I, Life Expectancy, Male, Mitosis, RNA, Bacterial, Signal Transduction, Caenorhabditis elegans
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