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Three Mutants That Extend Both Mean and Maximum Life Span of the Nematode, Caenorhabditis Elegans, Define the Age-1 Gene
Abstract
Long-lived mutants in the nematode Caenorhabditis elegans have been studied to determine if the mutations responsible for extended life were allelic. Three of four mutant strains studied (MK31, MK542, MK546) contain recessive mutations that significantly lengthen life; MK542 and MK546 consistently fail to complement the long life phenotype of age-1 and are therefore allelic. MK31, although longer lived than wild type, is equivocal, in some cases failing to complement age-1 but not in others. All three long-lived strains have reduced hermaphrodite self-fertility and also fail to complement for this presumed pleiotropic effect of the age-1 mutation. Each of these three strains also contains an independent mutation at unc-31 IV. Since the mutants were isolated in the same mutant hunt (Klass, 1983) using protocols that did not guarantee independence, the mutations cannot be assumed to be independently isolated.
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“The lifespan and healthspan of invertebrates are extended by mutations in pathways such as the DAF-2, a gene that encodes for the IGF-1 pathway in the nematode Caenorhabditis elegans (C. elegans), or the mTOR signaling pathways that are linked to accelerating the aging process (60, 62–65).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [62]
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Items 201–241 of 241
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“Early discoveries in the 20th century showed that the longevity of research animals could be extended by external factors such as caloric restriction [1, 2], and that mutations in specific genes, including age-1 from the insulin/IGF-1 signaling pathway, can significantly increase lifespan [3, 4].”
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“Later on, Friedman and Johnson (1988) or Kenyon et al. (1993) isolated other long-lived C. elegans mutants and mutations increasing lifespan were also discovered in D. melanogaster (e.g. Clancy et al. 2001) and mice (review in e.g. Bartke 2005).”
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“For example, age-1 and daf-2 extend life span by up to 100% [26, 27].”
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“Such view of the underlying causes of aging is presented in the classical works of Weissmann 1891; Medawar 1952; and other authors (Friedman and Johnson1988; Gavrilov and Gavrilova 2002; Goldsmith 2004; Guarente and Kenyon 2000; Johnson 1990; Keeley and Bond 1999; Lithgow et al. 1995; Miller 1999;…”
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“…that aging can be modified genetically was conducted using the free-living nematode C. elegans, in which loss-of-function mutations in the insulin/IGF-1 signalling (IIS) pathway resulted in the extension of the worm lifespan (Kenyon et al. 1993; Friedman & Johnson 1988; Kimura et al. 1997a).”
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Wu, Y., Duong, T., Rasmussen, N. R., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.15.699774
“The age-1(hx546) reduction-of-function mutation in C. elegans PI3Kcat was the first lifespan-191 extending mutation found in animals (Friedman & Johnson, 1988a, 1988b; Johnson, 1990; Klass, 1983).”
Wu, Y., Duong, T., Rasmussen, N. R., et al. (2026) · Aging Cell · doi:10.1111/acel.70571
“The age-1(hx546) reduction- of-function mutation in C. elegans PI3Kcat was the first lifespan-extending mutation found in animals (Friedman and Johnson 1988a, 1988b; Johnson 1990; Klass 1983).”
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Self-citationHormonal Influence and Modulation in Aging
Shimokawa, I. (2015) · Healthy ageing and longevity · doi:10.1007/978-3-319-14830-4_4
“The findings demonstrating that longevity can by achieved by inhibition of the anabolic pathway were first reported by Friedman and Johnson [5] in Caenorhabditis elegans.”
BackgroundTelomerase activity in human germline and embryonic tissues and cells
Wright, W. E., Piatyszek, M. A., Rainey, W. E., Byrd, W., & Shay, J. W. (1996) · Developmental Genetics · doi:10.1002/(sici)1520-6408(1996)18:2
Self-citation
Metadata
- Authors
- Friedman, D. B., & Johnson, T. E.
- Affiliations
- University of California, Irvine (US)
- ORCID
- Johnson, T. E.
- Venue
- Journal of Gerontology
- Publisher
- Oxford University Press (OUP)
- Published
- 1988-07-01
- Volume
- 43
- Issue
- 4
- Pages
- B102-B109
- ISSN
- 0022-1422 (ISSN-L)
- OpenAlex
- W1491447916
- Cited by
- 240
- References
- 0
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 4 · 2023: 2 · 2022: 6 · 2021: 11 · 2020: 9 · 2019: 5 · 2018: 11 · 2017: 4 · 2016: 15 · 2015: 10 · 2014: 8 · 2013: 8 · 2012: 8
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Science of Aging Knowledge Environment
- Funders
- National Science Foundation
- National Institute on Aging (AG05720, N01-AG-92113)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Nematode management and characterization studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- Caenorhabditis elegans, long-lived mutants, lifespan extension, allelic complementation, recessive mutations, self-fertility, unc-31, pleiotropy, aging
- MeSH terms
- Aging, Alleles, Animals, Caenorhabditis, Crosses, Genetic, Fertility, Genes, Genetic Complementation Test, Longevity, Male, Mutation, Phenotype, Disorders of Sex Development
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