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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The lifespan and healthspan of invertebrates are extended by mutations in pathways such as DAF-2, a gene that encodes for the IGF-1 pathway in C. elegans, or the mTOR signaling pathways that are linked to accelerating the aging process.
“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]
Cited by
Sorted by citations
The Role of Oxidative Stress in the Pathogenesis of Age-Related Macular Degeneration
Beatty, S., Koh, H.-H., Phil, M., Henson, D., & Boulton, M. (2000) · Survey of Ophthalmology · doi:10.1016/s0039-6257(00)00140-5 · Cited by 2,051 · see citing works
Genetic pathways that regulate ageing in model organisms
Guarente, L., & Kenyon, C. J. (2000) · Nature · doi:10.1038/35041700 · Cited by 1,337 · see citing works
Lithgow, G. J., White, T. M., Melov, S., & Johnson, T. E. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.16.7540 · Cited by 862 · see citing works
Self-citationAMP-Activated Protein Kinase (AMPK) Controls the Aging Process via an Integrated Signaling Network
Salminen, A., & Kaarniranta, K. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2011.12.005 · Cited by 860 · see citing works
Broughton, S. J., Piper, M. D. W., Ikeya, T., Bass, T. M., Jacobson, J., Driege, Y., Martinez, P., Hafen, E., Withers, D. J., Leevers, S. J., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405775102 · Cited by 822 · see citing works
Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds
Bonkowski, M. S., & Sinclair, D. A. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.93 · Cited by 834 · see citing works
Genetic analysis of ageing: role of oxidative damage and environmental stresses
Martin, G. M., Austad, S. N., & Johnson, T. E. (1996) · Nature Genetics · doi:10.1038/ng0596-25 · Cited by 641 · see citing works
Self-citationInsulin/insulin-like growth factor signaling in C. elegans
Murphy, C. T. (2013) · WormBook · doi:10.1895/wormbook.1.164.1 · Cited by 527 · see citing works
“…by Klass in a genetic screen for long-lived animals (Klass, 1983), and subsequent analysis by the Johnson lab suggested that the longevity phenotype in this mutant strain was due to a recessive mutation in a single gene (Friedman and Johnson, 1988b; Friedman and Johnson, 1988a; Johnson, 1990).”
Mutation in the silencing gene S/R4 can delay aging in S. cerevisiae
Kennedy, B. K., Austriaco, N. P. G., Zhang, J., & Guarente, L. (1995) · Cell · doi:10.1016/0092-8674(95)90499-9 · Cited by 499 · see citing works
“In Caenorhabditis elegans, a single mutation, age-l, extends the life span of the worm by 50% (Friedman and Johnson, 1988; Johnson, 1990).”
BackgroundIncreased Life-Span of age -1 Mutants in Caenorhabditis elegans and Lower Gompertz Rate of Aging
Johnson, T. E. (1990) · Science · doi:10.1126/science.2392681 · Cited by 414 · see citing works
Self-citationOxidative stress and ageing in Caenorhabditis elegans
Vanfleteren, J. R. (1993) · Biochemical Journal · doi:10.1042/bj2920605 · Cited by 383 · see citing works
Mitochondrial dysfunction as a cause of ageing
Trifunović, A., & Larsson, N. (2008) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2007.01905.x · Cited by 375 · see citing works
An Insulin-like Signaling Pathway Affects Both Longevity and Reproduction in Caenorhabditis elegans
Tissenbaum, H. A., & Ruvkun, G. (1998) · Genetics · doi:10.1093/genetics/148.2.703 · Cited by 354 · see citing works
Lifespan extension in C. elegans by a molecular chaperone dependent upon insulin‐like signals
Walker, G. A., & Lithgow, G. J. (2003) · Aging Cell · doi:10.1046/j.1474-9728.2003.00045.x · Cited by 303 · see citing works
“Mutation of the downstream age-1 gene, which encodes a protein similar to the mammalian p120 catalytic subunit of phosphatidylinositol 3-kinase, leads to a 65% increase in mean lifespan (Friedman & Johnson, 1988; Malone et al ., 1996; Morris et al ., 1996).”
BackgroundProduction of sperm reduces nematode lifespan
Voorhies, W. A. V. (1992) · Nature · doi:10.1038/360456a0 · Cited by 301 · see citing works
Mohammed, I., Hollenberg, M. D., Ding, H., & Triggle, C. R. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.718942 · Cited by 278 · see citing works
Longevity and heavy metal resistance in daf‐2 and age‐1 long‐lived mutants of Caenorhabditis elegans
Barsyte, D., Lovejoy, D. A., & Lithgow, G. J. (2001) · The FASEB Journal · doi:10.1096/fj.99-0966com · Cited by 270 · see citing works
“daf-28 extend life span by up to 100% (3, 5, 6).”
Steinkraus, K. A., Smith, E. D., Davis, C., Carr, D. T., Pendergrass, W. R., Sutphin, G. L., Kennedy, B. K., & Kaeberlein, M. R. (2008) · Aging Cell · doi:10.1111/j.1474-9726.2008.00385.x · Cited by 265 · see citing works
“…decrease IIS, such as loss of function alleles of insulin-like receptor daf-2 (Kenyon et al ., 1993; Kimura et al ., 1997) or the PI3-kinase age-1 (Friedman & Johnson, 1988a,b; Morris et al ., 1996), increase longevity via a mechanism that is dependent on the FOXO-family transcription factor…”
BackgroundHealthful aging mediated by inhibition of oxidative stress
Vatner, S. F., Zhang, J., Oydanich, M. K., Berkman, T., Naftalovich, R., & Vatner, D. E. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101194 · Cited by 239 · see citing works
Stress resistance as a determinate of C. elegans lifespan
Lithgow, G. J., & Walker, G. A. (2002) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00422-5 · Cited by 212 · see citing works
Remarkable longevity and stress resistance of nematode PI3K‐null mutants
Ayyadevara, S., Alla, R., Thaden, J. J., & Reis, R. J. S. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00348.x · Cited by 205 · see citing works
“Age-1(hx546) is a reduction-of-function mutation (Friedman & Johnson, 1988a), for which the sequence alteration had not previously been identified.”
BackgroundInfluentialEvolution of lifespan in C. elegans
Walker, D. W., McColl, G., Jenkins, N. L., Harris, J., & Lithgow, G. J. (2000) · Nature · doi:10.1038/35012693 · Cited by 207 · see citing works
SMK-1, an Essential Regulator of DAF-16-Mediated Longevity
Wolff, S., Ma, H., Burch, D., Maciel, G. A. R., Hunter, T. R., & Dillin, A. G. (2006) · Cell · doi:10.1016/j.cell.2005.12.042 · Cited by 205 · see citing works
“Loss-of-function mutations in IIS signaling cause precocious entry into diapause and increased longevity (Friedman and Johnson, 1988a, 1988b; Hertweck et al., 2004; Kenyon et al., 1993; Paradis et al., 1999; Paradis and Ruvkun, 1998).”
BackgroundEvolutionary Theories of Aging and Longevity
Gavrilov, L. A., & Gavrilova, N. S. (2002) · The Scientific World JOURNAL · doi:10.1100/tsw.2002.96 · Cited by 201 · see citing works
“As a result of this triumphant evolutionary indoctrination, many exciting research opportunities for lifespan extension were squandered for half a century until the recent and astonishing discovery of single-gene mutants with profoundly extended longevity was ultimately made [95,96,97,98,99,100,101], despite all disco…”
BackgroundLifespan-regulating genes in C. elegans
Uno, M., & Nishida, E. (2016) · npj Aging and Mechanisms of Disease · doi:10.1038/npjamd.2016.10 · Cited by 192 · see citing works
“elegans homolog of phosphatidylinositol 3-kinase, are also associated with increased longevity.(8,9) Longevity induced by a reduction in IIS signaling is entirely dependent on DAF-16, the C.”
BackgroundLongevity and stress in Caenorhabditis elegans
Zhou, K. I., Pincus, Z., & Slack, F. J. (2011) · Aging · doi:10.18632/aging.100367 · Cited by 189 · see citing works
“exhibits normal fertility levels, although it has a significant reduction in early fertility [93, 203], and the fertility of the long-lived age-1 mutant is not significantly different from wild-type [12, 204, 205].”
BackgroundMechanisms of life span determination in Caenorhabditis elegans☆
Vanfleteren, J. R., & Braeckman, B. P. (1999) · Neurobiology of Aging · doi:10.1016/s0197-4580(99)00087-1 · Cited by 181 · see citing works
“Two alleles, hx542 and hx546 (now believed to be identical), prolonged the mean life span by 65%, without affecting the rate of development, motility, or fertility [28, 29].”
BackgroundHuman longevity: Genetics or Lifestyle? It takes two to tango
Passarino, G., Rango, F. D., & Montesanto, A. (2016) · Immunity & Ageing · doi:10.1186/s12979-016-0066-z · Cited by 178 · see citing works
“Subsequently, Tom Johnson found out that most of the mutants with long lifespan had mutations in the age1 gene [4].”
Adachi, H., Fujiwara, Y., & Ishii, N. (1998) · The Journals of Gerontology Series A · doi:10.1093/gerona/53a.4.b240 · Cited by 178 · see citing works
Johnson, T. E., Henderson, S. T., Murakami, S., de Castro, E., de Castro, S. H., Cypser, J. R., Rikke, B. A., Tedesco, P., & Link, C. D. (2002) · Journal of Inherited Metabolic Disease · doi:10.1023/a:1015677828407 · Cited by 174 · see citing works
“25 (2002) 70% longer than wild-type and a maximum lifespan that is 105% longer (Friedman and Johnson 1988a; Johnson 1990). age-1 mutations have little e¡ect on fertility, length of reproduction or rate of development (Duhon et al 1996; Friedman and Johnson 1988a,b; Johnson and Lithgow 1992; Johnson…”
BackgroundSelf-citationProtein Degradation by the Proteasome and Its Implications in Aging
Friguet, B., Bulteau, A., Chondrogianni, N., Conconi, M., & Petropoulos, I. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06643.x · Cited by 172 · see citing works
Partridge, L. (2009) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2009.0222 · Cited by 167 · see citing works
“Subsequent work with these mutations (Friedman & Johnson 1988), and further screening (Kenyon et al. 1993), revealed that it was possible to double the lifespan of the worm with a mutation in a single gene.”
BackgroundSignaling networks determining life span
Riera, C. E., Merkwirth, C., De Magalhaes Filho, C. D., & Dillin, A. (2016) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014451 · Cited by 161 · see citing works
“elegans as mutations of age-1; phosphatidylinositol 3-kinase (PI3K), a downstream effector of insulin/insulin-like signaling; and daf-2, the insulin/insulin-like receptor (4, 5).”
BackgroundAge-associated changes in expression of small, noncoding RNAs, including microRNAs, in C. elegans
Kato, M., Chen, X., Inukai, S., Zhao, H., & Slack, F. J. (2011) · RNA · doi:10.1261/rna.2714411 · Cited by 156 · see citing works
“…cause a delay in the aging process and extend lifespan. age-1 and daf-2, both of which encode components in an insulin signaling cascade, cause more than a twofold increase in lifespan when either activity is reduced (Klass 1983; Friedman and Johnson 1988; Kenyon et al. 1993; Morris et al. 1996).”
BackgroundBowen, R. L., & Atwood, C. (2004) · Gerontology · doi:10.1159/000079125 · Cited by 155 · see citing works
Hormesis and aging in Caenorhabditis elegans
Cypser, J. R., Tedesco, P., & Johnson, T. E. (2006) · Experimental Gerontology · doi:10.1016/j.exger.2006.09.004 · Cited by 143 · see citing works
“Mutations in age-1 or daf-2 increase both life expectancy (Friedman and Johnson 1988a, b; Kenyon et al., 1993) and stress resistance (Barsyte et al., 2001; Larsen 1993; Lithgow et al., 1994, 1995; Murakami and Johnson, 1996; Vanfleteren 1993), and mutations in daf-16 or daf-18 suppress both the…”
BackgroundSelf-citationHunter, T., BANNISTER, W. H., & Hunter, G. J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.45.28652 · Cited by 142 · see citing works
Role of FoxO transcription factors in aging and age-related metabolic and neurodegenerative diseases
Du, S., & Zheng, H. (2021) · Cell & Bioscience · doi:10.1186/s13578-021-00700-7 · Cited by 140 · see citing works
Strategies and Challenges in Clinical Trials Targeting Human Aging
Newman, J. C., Milman, S., Hashmi, S. K., Austad, S. N., Kirkland, J. L., Halter, J. B., & Barzilai, N. (2016) · The Journals of Gerontology Series A · doi:10.1093/gerona/glw149 · Cited by 137 · see citing works
“In the decades that have passed since the first single genes were identified that regulate longevity in an organism (6,7), a variety of pathways have been discovered that, if manipulated, are associated with life-span and health-span extension.”
BackgroundHeat Shock Protein Accumulation Is Upregulated in a Long-Lived Mutant of Caenorhabditis elegans
Walker, G. A., White, T. M., McColl, G., Jenkins, N. L., Babich, S. L., Candido, E. P. M., Johnson, T. E., & Lithgow, G. J. (2001) · The Journals of Gerontology Series A · doi:10.1093/gerona/56.7.b281 · Cited by 135 · see citing works
Self-citationDrugs that modulate aging: the promising yet difficult path ahead
Kennedy, B. K., & Pennypacker, J. K. (2014) · Translational research · doi:10.1016/j.trsl.2013.11.007 · Cited by 127 · see citing works
“It was clear from these studies that extending lifespan was possible through methods such as mutagenesis and screening (10, 12, 20), or through selection, for instance, by isolating flies that maintain late”
BackgroundMethodMalone, E. A., Inoue, T., & Thomas, J. H. (1996) · Genetics · doi:10.1093/genetics/143.3.1193 · Cited by 126 · see citing works
Kleemeier Award Lecture: Are There Genes for Aging?
Miller, R. A. (1999) · The Journals of Gerontology Series A · doi:10.1093/gerona/54.7.b297 · Cited by 124 · see citing works
Genetics, Life Span, Health Span, and the Aging Process in Caenorhabditis elegans
Tissenbaum, H. A. (2012) · The Journals of Gerontology Series A · doi:10.1093/gerona/gls088 · Cited by 118 · see citing works
Johnson, T. E., Cypser, J. R., de Castro, E., Castro, S., Henderson, S. T., Murakami, S., Rikke, B. A., Tedesco, P., & Link, C. D. (2000) · Experimental Gerontology · doi:10.1016/s0531-5565(00)00138-8 · Cited by 115 · see citing works
Self-citationVanfleteren, J. R., & Vreese, A. D. (1996) · Journal of Experimental Zoology · doi:10.1002/(sici)1097-010x(19960201)274:2 · Cited by 117 · see citing works
Increased frequency of deletions in the mitochondrial genome with age ofCaenorhabditis elegans
Melov, S., Lithgow, G. J., Fischer, D. R., Tedesco, P., & Johnson, T. E. (1995) · Nucleic Acids Research · doi:10.1093/nar/23.8.1419 · Cited by 116 · see citing works
Self-citationGruber, J., Ng, L. F., Poovathingal, S. K., & Halliwell, B. B. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.09.051 · Cited by 111 · see citing works
Insulin-like signaling, metabolism, stress resistance and aging in Caenorhabditis elegans
Braeckman, B. P. (2001) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00222-6 · Cited by 110 · see citing works
What Can We Learn About Human Disease from the Nematode C. elegans?
Apfeld, J., & Alper, S. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-7471-9_4 · Cited by 108 · see citing works
“Three of these mutations were subsequently mapped and shown to be in the same genetic locus, named age-1 [98, 99].”
BackgroundArden, K. C., & Biggs, W. (2002) · Archives of Biochemistry and Biophysics · doi:10.1016/s0003-9861(02)00207-2 · Cited by 107 · see citing works
Antiaging agents: safe interventions to slow aging and healthy life span extension
Liu, J. (2022) · Natural Products and Bioprospecting · doi:10.1007/s13659-022-00339-y · Cited by 107 · see citing works
“The discovery of age-1, the first gene in nematodes to regulate life span, led to an explosion in the study of aging in this system [193, 194].”
BackgroundAbsence of strong heterosis for life span and other life history traits in Caenorhabditis elegans.
Johnson, T. E., & Hutchinson, E. W. (1993) · Genetics · doi:10.1093/genetics/134.2.465 · Cited by 103 · see citing works
Self-citationRattray, N. J. W., Trivedi, D. K., Yun Xu, A., Chandola, T., Johnson, C. H., Marshall, A. D., Mekli, K., Rattray, Z., Tampubolon, G., Vanhoutte, B., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12716-2 · Cited by 100 · see citing works
The hypothalamus for whole-body physiology: from metabolism to aging
Liu, T., Xu, Y., Yi, C., Tong, Q., & Cai, D. (2021) · Protein & Cell · doi:10.1007/s13238-021-00834-x · Cited by 103 · see citing works
“The mutants that regulate the activity of these signaling components have significant effects on increasing the lifespan of C. elegans (Friedman and Johnson, 1988a, b; Kenyon et al., 1993).”
BackgroundCarbonylated proteins in aging and exercise: immunoblot approaches
Goto, S., Nakamura, A., Radak, Z. O., Nakamoto, H., Takahashi, R., Yasuda, K., Sakurai, Y., & Ishii, N. (1999) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(98)00133-x · Cited by 102 · see citing works
“A number of mutants have been isolated which exhibit either long or short life-spans (Friedman and Johnson, 1988; Ishii et al., 1990; Kenyon et al., 1993).”
Towards an e-biology of ageing: integrating theory and data
Kirkwood, T. B. L., Boys, R. J., Gillespie, C. S., Proctor, C. J., Shanley, D. P., & Wilkinson, D. J. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1051 · Cited by 100 · see citing works
Gruber, J., Ng, L. F., Fong, S., Wong, Y. T., Koh, S. A., Chen, C.-B., Shui, G., Cheong, W. F., Schaffer, S., Wenk, M. R., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019444 · Cited by 96 · see citing works
“elegans [17], a large amount of data has been generated regarding ageing and its genetic determinants in nematodes [14,18].”
BackgroundPromoting longevity by maintaining metabolic and proliferative homeostasis
Wang, L., Karpac, J., & Jasper, H. (2013) · Journal of Experimental Biology · doi:10.1242/jeb.089920 · Cited by 91 · see citing works
“Insight into the role of insulin signaling in regulating lifespan was first obtained from genetic screens in worms, in which mutations in the PI3K homologue AGE-1 were identified that extend lifespan by more than 100% (Friedman and Johnson, 1988).”
BackgroundProspects for Life Span Extension
Sierra, F., Hadley, E., Suzman, R., & Hodes, R. J. (2009) · Annual Review of Medicine · doi:10.1146/annurev.med.60.061607.220533 · Cited by 90 · see citing works
DAF-16 target identification in C. elegans: past, present and future
Tullet, J. M. A. (2014) · Biogerontology · doi:10.1007/s10522-014-9527-y · Cited by 87 · see citing works
“Mutation of the age-1 gene (the worm phosphatidylinositol 3-kinase homologue which acts downstream of daf2) can also increase adult lifespan by up to tenfold (Ayyadevara et al. 2008; Friedman and Johnson 1988).”
BackgroundThe Evolution of Programmed Death in a Spatially Structured Population
Travis, J. M. J. (2004) · The Journals of Gerontology Series A · doi:10.1093/gerona/59.4.b301 · Cited by 85 · see citing works
Glycine promotes longevity in Caenorhabditis elegans in a methionine cycle-dependent fashion
Liu, Y. J., Janssens, G. E., McIntyre, R. L., Molenaars, M., Kamble, R., Gao, A. W., Jongejan, A., van Weeghel, M., MacInnes, A. W., & Houtkooper, R. H. (2019) · PLoS Genetics · doi:10.1371/journal.pgen.1007633 · Cited by 80 · see citing works
“elegans identified longevity-associated genes and provided us with great insights into the plasticity of aging (1-3).”
BackgroundLidzbarsky, G. A., Gutman, D., Shekhidem, H. A., Sharvit, L. E., & Atzmon, G. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00104 · Cited by 80 · see citing works
“Mutations in this gene cause delay in age-related deterioration of body movement and muscle deterioration a twofold extension of the life span (17, 101, 102).”
BackgroundCaloric restriction and lifespan: a role for protein turnover?
Tavernarakis, N., & Driscoll, M. (2002) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00341-4 · Cited by 76 · see citing works
Tullet, J. M. A., Araiz, C., Sanders, M. J., Au, C., Benedetto, A., Papatheodorou, I., Clark, E. H., Schmeißer, K., Jones, D., Schuster, E. F., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004109 · Cited by 74 · see citing works
“In Caenorhabditis elegans , it has long been known that reduction of insulin/IGF-1 signaling (IIS) increases lifespan [1–3], reviewed in [4].”
Chen, A. T., Guo, C., Itani, O. A., Budaitis, B. G., Williams, T. W., Hopkins, C. E., McEachin, R. C., Pande, M., Grant, A. R., Yoshina, S., et al. (2015) · Genetics · doi:10.1534/genetics.115.177998 · Cited by 73 · see citing works
“Theconservedroleof IGFRsignalingandFoxOtranscription factors in life span control was first discovered in C. elegans (Friedman and Johnson 1988a,b; Johnson 1990; Kenyon et al. 1993).”
BackgroundMouchiroud, L., Molin, L., Dallière, N., & Solari, F. (2010) · BioFactors · doi:10.1002/biof.127 · Cited by 73 · see citing works
“Initial evidence for gene impact on life span came from the work done in late 80s with the nematode Caenorhabditis elegans, in which mutations that reduce the activity of the PI3 kinase ortholog AGE-1 [1] or of the insulin/IGF-1 receptor (IIR) can double average life span [2].”
BackgroundInvertebrate gerontology: The age mutations of Caenorhabditis elegans
Lithgow, G. J. (1996) · BioEssays · doi:10.1002/bies.950181007 · Cited by 72 · see citing works
Pleiotropic action of parasites: How to be good for the host
Michalakis, Y., Olivieri, I., Renaud, F., et al. (1992) · Trends in Ecology & Evolution · doi:10.1016/0169-5347(92)90108-n · Cited by 72 · see citing works
P-element inserts in transgenic flies: a cautionary tale
Kaiser, M., GASSER, M., Ackermann, R., et al. (1997) · Heredity · doi:10.1038/hdy.1997.1 · Cited by 72 · see citing works
Pharmacological lifespan extension of invertebrates
Lucanic, M., Lithgow, G. J., & Alavez, S. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2012.06.006 · Cited by 70 · see citing works
Oxidative stress and aging inCaenorhabditis elegans
Ishii, N. (2000) · Free Radical Research · doi:10.1080/10715760000301371 · Cited by 66 · see citing works
Johnson, T. E., & Lithgow, G. J. (1992) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1992.tb01993.x · Cited by 65 · see citing works
Self-citationThe genetics of ageing: insight from genome‐wide approaches in invertebrate model organisms
Kennedy, B. K. (2008) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2007.01903.x · Cited by 63 · see citing works
Metabolic regulation of lifespan from a C. elegans perspective
Dall, K. B., & Færgeman, N. J. (2019) · Genes & Nutrition · doi:10.1186/s12263-019-0650-x · Cited by 62 · see citing works
“Klass and coworkers originally identified a class of longevity mutants [9], which later were found to share the same unique genetic locus, which was named age-1 [10, 11], encoding the catalytic subunit of phosphatidylinositol 3-kinase (PI3K).”
BackgroundJohnson, T. E., Tedesco, P. M., & Lithgow, G. J. (1993) · Genetica · doi:10.1007/bf01435988 · Cited by 63 · see citing works
Self-citationSavory, F. R., Sait, S. M., & Hope, I. A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024550 · Cited by 60 · see citing works
“Caenorhabditis elegans [2,3,4,5], Drosophila melanogaster [6,7] and mice, Mus musculus [8], and may also influence lifespan in humans [9,10].”
BackgroundDevelopmental Drift and the Role of Wnt Signaling in Aging
Gruber, J., Yee, Z., & Tolwinski, N. S. (2016) · Cancers · doi:10.3390/cancers8080073 · Cited by 60 · see citing works
Review of Genetic Investigations into the Aging Processes of Drosophila
Arking, R., & Dudas, S. P. (1989) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1989.tb02240.x · Cited by 59 · see citing works
The interplay between mitochondria and autophagy and its role in the aging process
Schiavi, A., & Ventura, N. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.02.015 · Cited by 59 · see citing works
“Since the discovery of the first gerontogene in the nematode Caenorhabditis elegans (Friedman and Johnson, 1988), many genes have been identified that, when singularly mutated, affect lifespan.”
BackgroundGolden, T. R., Beckman, K. B., Lee, A. H. J., Dudek, N., Hubbard, A., Samper, E., & Melov, S. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00273.x · Cited by 56 · see citing works
The role of mitochondria in <scp>mTOR</scp>‐regulated longevity
Wei, Y., Zhang, Y., Cai, Y., & Xu, M. (2015) · Biological Reviews · doi:10.1111/brv.12103 · Cited by 56 · see citing works
“Firstly, in the 1980s and 1990s, several groups applying forward genetic screens in C. elegans using chemical mutagens identified many lifespan genes (genes that modulate lifespan) such as age-1, eat-2, daf-2, daf-16 etc. (Friedman & Johnson, 1988; Kenyon et al., 1993; Lakowski & Hekimi, 1998).”
BackgroundBiogerontology: research status, challenges and opportunities.
Rattan, S. I. S. (2018) · Acta bio-medica dell'Ateneo parmense/Acta biomedica · doi:10.23750/abm.v89i2.7403 · Cited by 54 · see citing works
Effects of the mitochondrial respiratory chain on longevity in C. elegans
Rabbitts, B. M., Sedensky, M. M., & Morgan, P. G. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.03.028 · Cited by 53 · see citing works
Aging, Longevity, and Cancer: Studies in Down's Syndrome and Centenariansa
Franceschi, C., Monti, D., Cossarizza, A., Fagnoni, F. F., Passeri, G., & Sansoni, P. (1991) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1991.tb16997.x · Cited by 53 · see citing works
Uno, M., Tani, Y., Nono, M., Okabe, E., Kishimoto, S., Takahashi, C., Abe, R., Kurihara, T., & Nishida, E. (2021) · iScience · doi:10.1016/j.isci.2021.102706 · Cited by 54 · see citing works
Evolving dispersal and age at death
Dytham, C., & Travis, J. M. J. (2006) · Oikos · doi:10.1111/j.2006.0030-1299.14395.x · Cited by 50 · see citing works
Hormesis in Caenorhabditis elegans dauer-defective mutants
Cypser, J. R., & Johnson, T. E. (2003) · Biogerontology · doi:10.1023/a:1025138800672 · Cited by 51 · see citing works
“Mutations in age-1 provided the first example of life-extension via a single-gene approach (Klass 1983; Friedman and Johnson 1988a, b; Johnson 1990).”
BackgroundSelf-citationSIR2 and aging – the exception that proves the rule
Guarente, L. (2001) · Trends in Genetics · doi:10.1016/s0168-9525(01)02339-3 · Cited by 49 · see citing works
Ageing selected for its own sake
Mitteldorf, J. (2004) · Evolutionary ecology research · Cited by 49 · see citing works
Protein synthesis elongation factor EF-1 alpha expression and longevity in Drosophila melanogaster.
Shikama, N., Ackermann, R., & Brack, C. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.10.4199 · Cited by 49 · see citing works
Kim, S.-H., Kim, B.-K., Park, S.-H., & Park, S.-K. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/2860642 · Cited by 46 · see citing works
“The first long-lived mutant reported was age-1 mutant [46].”
Pl3-kinase inhibition induces dauer formation, thermotolerance and longevity in C. elegans☆
Babar, P., Adamson, C., Walker, G. A., et al. (1999) · Neurobiology of Aging · doi:10.1016/s0197-4580(99)00094-9 · Cited by 46 · see citing works
Pinkas, A., & Aschner, M. (2016) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.6b00034 · Cited by 45 · see citing works
Effects of Curcumin on Aging: Molecular Mechanisms and Experimental Evidence
Bahrami, A., Montecucco, F., Carbone, F., & Sahebkar, A. (2021) · BioMed Research International · doi:10.1155/2021/8972074 · Cited by 41 · see citing works
“elegans, longevity is widely determined by the expression of the Age-1 gene [123, 124].”
Age influences resistance ofCaenorhabditis elegansto killing by pathogenic bacteria
Laws, T. R., Harding, S. V., Smith, M. P., Atkins, T. P., & Titball, R. W. (2004) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2004.tb09545.x · Cited by 41 · see citing works
Du, S., Jin, F., Maneix, L., Gedam, M., Xu, Y., Catic, A., Wang, M. C., & Zheng, H. (2021) · Aging Cell · doi:10.1111/acel.13432 · Cited by 42 · see citing works
“In both Caenorhabditis elegans and Drosophila melanogaster, reduction of IIS signaling leads to extended lifespan, and this effect requires FoxO/DAF16 and dFOXO, respectively (Friedman & Johnson, 1988; Friedman & Johnson, 1988; Kenyon et al., 1993; Woodling et al., 2020).”
BackgroundCaenorhabditis elegans—a paradigm for aging research: advantages and limitations
Gershon, H. E., & Gershon, D. (2002) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00401-8 · Cited by 40 · see citing works
Age influences resistance of Caenorhabditis elegans to killing by pathogenic bacteria
Laws, T. R., Harding, S. V., Smith, M. P., Atkins, T. P., & Titball, R. W. (2004) · FEMS Microbiology Letters · doi:10.1016/j.femsle.2004.03.034 · Cited by 48 · see citing works
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
