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Additionally, a locus on chromosome 2 and another on chromosome 6 have been associated with longevity.", + "context": { + "0c6c0977-2cf9-4bbf-bc31-fe025f008089": [ + { + "document_id": "0c6c0977-2cf9-4bbf-bc31-fe025f008089", + "text": "DOI: https://doi.org/10.7554/eLife.75244\n\n\b\n\n24 of 30\nChromosomes and Gene Expression | Genetics and Genomics\n\nResearch article\nContinued\nAuthor(s)\n\nYear\n\nDataset title\n\nDataset URL\n\nDatabase and Identifier\n\nLongevityteam\n\n2021\n\nGenetics of longevity in\nBXD mice\n\nhttp://www.\nBDL_10006, 10006\ngenenetwork.org/\nshow_trait?trait_id=\n10006&dataset=BXD-\nLongevityPublish\n\nLongevityteam\n\n2021\n\nGenetics of longevity in\nBXD mice\n\nhttp://www.\nBDL_10010, 10010\ngenenetwork.org/\nshow_trait?trait_id=\n10010&dataset=BXD-\nLongevityPublish\n\nLongevityteam\n\n2021\n\nGenetics of longevity in\nBXD mice\n\nhttp://www.\nBDL_10011, 10011\ngenenetwork.org/\nshow_trait?trait_id=\n10011&dataset=BXD-\nLongevityPublish\n\nLongevityteam\n\n2020\n\nGenetics of longevity in\nBXD mice\n\nhttp://www.\nBDL_10021, 10021\ngenenetwork.org/\nshow_trait?trait_id=\n10021&dataset=BXD-\nLongevityPublish\n\nLongevityteam\n\n2020\n\nGenetics of longevity in\nBXD mice\n\nhttp://www.\nBDL_10022, 10022\ngenenetwork.org/\nshow_trait?trait_id=\n10022&dataset=BXD-\nLongevityPublish\n\nLongevityteam\n\n2020\n\nGenetics of longevity in\nBXD mice\n\nhttp://www.\nBDL_10025, 10025\ngenenetwork.org/\nshow_trait?trait_id=\n10025&dataset=BXD-\nLongevityPublish\n\nLongevityteam\n\n2021\n\nGenetics and epigenetics\nof aging and longevity in\nBXD mice\n\nhttp://www.\nBDL_10066, 10066\ngenenetwork.org/\nshow_trait?trait_id=\n10066&dataset=BXD-\nLongevityPublish\n\nReferences\nAlbertsen HM, Smith SA, Mazoyer S, Fujimoto E, Stevens J, Williams B, Rodriguez P, Cropp CS, Slijepcevic P,\nCarlson M. 1994." + } + ], + "2464a084-1a11-44eb-8bce-4b344de049ff": [ + { + "document_id": "2464a084-1a11-44eb-8bce-4b344de049ff", + "text": "DOI: https://doi.org/10.7554/eLife.75244\n\n\b\n\n24 of 30\nChromosomes and Gene Expression | Genetics and Genomics\n\nResearch article\nContinued\nAuthor(s)\n\nYear\n\nDataset title\n\nDataset URL\n\nDatabase and Identifier\n\nLongevityteam\n\n2021\n\nGenetics of longevity in\nBXD mice\n\nhttp://www.\nBDL_10006, 10006\ngenenetwork.org/\nshow_trait?trait_id=\n10006&dataset=BXD-\nLongevityPublish\n\nLongevityteam\n\n2021\n\nGenetics of longevity in\nBXD mice\n\nhttp://www.\nBDL_10010, 10010\ngenenetwork.org/\nshow_trait?trait_id=\n10010&dataset=BXD-\nLongevityPublish\n\nLongevityteam\n\n2021\n\nGenetics of longevity in\nBXD mice\n\nhttp://www.\nBDL_10011, 10011\ngenenetwork.org/\nshow_trait?trait_id=\n10011&dataset=BXD-\nLongevityPublish\n\nLongevityteam\n\n2020\n\nGenetics of longevity in\nBXD mice\n\nhttp://www.\nBDL_10021, 10021\ngenenetwork.org/\nshow_trait?trait_id=\n10021&dataset=BXD-\nLongevityPublish\n\nLongevityteam\n\n2020\n\nGenetics of longevity in\nBXD mice\n\nhttp://www.\nBDL_10022, 10022\ngenenetwork.org/\nshow_trait?trait_id=\n10022&dataset=BXD-\nLongevityPublish\n\nLongevityteam\n\n2020\n\nGenetics of longevity in\nBXD mice\n\nhttp://www.\nBDL_10025, 10025\ngenenetwork.org/\nshow_trait?trait_id=\n10025&dataset=BXD-\nLongevityPublish\n\nLongevityteam\n\n2021\n\nGenetics and epigenetics\nof aging and longevity in\nBXD mice\n\nhttp://www.\nBDL_10066, 10066\ngenenetwork.org/\nshow_trait?trait_id=\n10066&dataset=BXD-\nLongevityPublish\n\nReferences\nAlbertsen HM, Smith SA, Mazoyer S, Fujimoto E, Stevens J, Williams B, Rodriguez P, Cropp CS, Slijepcevic P,\nCarlson M. 1994." + } + ], + "43d5140a-ad39-438e-8ba6-76dd3c7c42bc": [ + { + "document_id": "43d5140a-ad39-438e-8ba6-76dd3c7c42bc", + "text": "Leduc MS, Hageman RS, Meng Q et al (2010) Identification of\ngenetic determinants of IGF-1 levels and longevity among mouse\ninbred strains. Aging Cell 9(5):823–836. doi:10.1111/j.14749726.2010.00612.x\n10. Lang DH, Gerhard GS, Griffith JW et al (2010) Quantitative trait\nloci (QTL) analysis of longevity in C57BL/6J by DBA/2J (BXD)\nrecombinant inbred mice. Aging Clin Exp Res 22(1):8–19\n11. Gelman R, Watson A, Bronson R et al (1988) Murine chromosomal\nregions\ncorrelated\nwith\nlongevity. Genetics\n118(4):693–704\n12. Jackson AU, Galecki AT, Burke DT et al (2002) Mouse loci\nassociated with life span exhibit sex-specific and epistatic effects." + }, + { + "document_id": "43d5140a-ad39-438e-8ba6-76dd3c7c42bc", + "text": "Conclusions These results suggest a novel locus influencing survival in the B6/D2 genetic background, perhaps\nvia a metabolic disorder that emerges by 200 days of age in\nmale animals. Keywords\nPathology\n\nLongevity \\ Lifespan \\ Mouse \\ Linkage \\\n\nIntroduction\nLongevity, the quintessential complex trait, likely reflects\nall aspects of an organism’s life history. In humans, the\nestimated heritability of age at death is estimated at\n25–33 % [1]. Genetic contributions to mortality rates are thus of great interest and may aid in the understanding of\ndisease etiology and the process of aging itself [2]." + }, + { + "document_id": "43d5140a-ad39-438e-8ba6-76dd3c7c42bc", + "text": "Here, we have extended this analysis to search for\ngenotypes related to survival to the age of 800 days in a\npopulation of a reciprocal F2 cross between (B6) and (D2)\nmice. Since QTL for longevity in mice have shown strong\nsex specificity [10, 12], we conducted sex-specific analyses. In addition, we also determined whether there were\nany change in pathology changes associated with the loci\nthat showed frequency distortions with aging. To confirm\nthe associations of the loci of interest with longevity and\npathology, we performed replication analyses on a panel of\nBXD recombinant inbred strains." + } + ], + "64886b4e-8599-4f61-84e6-9add7663a1b3": [ + { + "document_id": "64886b4e-8599-4f61-84e6-9add7663a1b3", + "text": "352(6291): p. aad0189. Liao, C.Y. , et al. , Genetic variation in the murine lifespan response to dietary restriction: from life extension to life\nshortening. Aging Cell, 2010. 9(1): p. 92-5. Johnson, M., Laboratory Mice and Rats. Mater. Methods, 2012. 2: p. 113. Fontaine, D.A. and D.B. Davis, Attention to Background Strain Is Essential for Metabolic Research: C57BL/6 and\nthe International Knockout Mouse Consortium. Diabetes, 2016. 65(1): p. 25-33. Simon, M.M. , et al. , A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains. Genome Biol, 2013. 14(7): p. R82. Lilue, J., et al." + } + ], + "8dad24f7-b658-44fa-af65-6f33db69c15a": [ + { + "document_id": "8dad24f7-b658-44fa-af65-6f33db69c15a", + "text":"Mamm Genome 2001;12: 930–2. 21 Gelman R, Watson A, Bronson R, Yunis E. Murine chromosomal\nregions correlated with longevity. Genetics 1988;118:693–704. 22 Peirce JL, Lu L, Gu J, Silver LM, Williams RW. A new set of BXD\nrecombinant inbred lines from advanced intercross populations in\nmice. BMC Genet 2004;5:7. 23 Rahman ZS, Tin SK, Buenaventura PN et al. A novel susceptibility\nlocus on chromosome 2 in the (New Zealand Black \\ New Zealand\nWhite) F1 hybrid mouse model of systemic lupus erythematosus. J Immunol 2002;168:3042–9. 24 Kono DH, Burlingame RW, Owens DG et al." + } + ], + "958b37c9-9bd5-4e84-939d-8f12dccf1055": [ + { + "document_id": "958b37c9-9bd5-4e84-939d-8f12dccf1055", + "text": "Conversely, the BXD strain with the shortest life span\n(BXD14) has the lowest responsiveness to the stimulatory effect of\nTGF-2 when old (48). The region on chromosome 2 where a\nsuggestive QTL regulating the responsiveness to TGF-2 in old\nmice is located also contains two QTL for longevity (32). Finally,\nthe strongest support for this hypothesis is the correlation between\nlongevity and the age-related increase in the serum-dependent effect of TGF-2 on LSK cells, the extent of which may determine\nstem cell function in aged mice." + } + ], + "98ce73c6-a53b-486f-8326-4b0bd47ec22e": [ + { + "document_id": "98ce73c6-a53b-486f-8326-4b0bd47ec22e", + "text": "\n\nFIGURE 8-5 Genetic regulation of longevity in mice stratified by cause of death.Female mice that inherit the C3H allele at D2Mit58 plus the BALB allele at D16Mit182 (light gray bars) have significantly higher longevity than their sisters (dark gray bars) with the C57BL/6 plus DBA/2 allele combination (\"all causes\" of death combined).Subsets of mice that died either of cancer or of a nonneoplastic (\"benign\") illness both show the association between genotype and longevity.Among the mice dying of neoplasia, subsets dying of lymphoma or of fibrosarcoma show equivalent, and significant, genotypic effects.Bars indicate means plus standard error of the mean.SOURCE:Miller et al. (unpublished results)." + }, + { + "document_id": "98ce73c6-a53b-486f-8326-4b0bd47ec22e", + "text": "\n\nThe available dataset also provides examples in which genetic variants seem to influence the risk of specific late-life diseases.Figure 8-6, for example, shows longevity results for mice stratified by their inheritance at the 12th chromosome locus D12Mit167.This is a locus associated with differential longevity in both male and female mice, with the strongest effect (adjusted p < 0.01) seen in those mice living more than 657 days (Jackson et al., unpublished results).The longest-lived mice are those that inherit both the C57BL/6 allele from their mother and the C3H allele from their father; on average, they survive 93 days longer than siblings with the BALB plus C3H combination.Figure 8-6 shows that the D12Mit167, like the pair of loci illustrated in Figure 8-5, has significant and similar effects in mice dying of cancer (85 days) and in mice dying of non-neoplastic diseases (126 days).A more detailed analysis of the cancers, however, suggests that while lymphoma and hepatoma victims are equally protected by the favorable alleles (effect sizes of 93 and 167 days, respec- mice of two subgroups: those dying of the urinary syndrome MUS, and those dying of all other causes.The genetic analysis contrasts mice with both the C57BL/6 allele at D4Mit84 and the C3H allele at D9Mit110 to mice with any of the three other allele combinations.In the males dying of causes other than MUS, this allele pair is associated with a 170-day increment in longevity (post-hoc p < 0.00003).But for males that do die of MUS, the same allele combination is associated with a 187-day decline in mean life span (post-hoc p < 0.03).This effect is thus pleiotropic, in that these alleles accelerate death in mice susceptible to MUS, while postponing death for all other males in the population.Although these loci are associated with differential longevity in mice that do develop MUS, they do not have a significant effect on the chances that MUS will indeed occur (not shown).The risk of developing MUS seems to be under control of a separate locus on chromosome 6.As shown in the bottom panel of Figure 8-7, males that inherit the C3H allele at D6Mit268 are far more likely to develop MUS (28 percent risk) than are their brothers who receive the DBA/2 allele at this locus (7 percent risk; p = 0.012 by two-tailed Fisher's exact test)." + }, + { + "document_id": "98ce73c6-a53b-486f-8326-4b0bd47ec22e", + "text": "\n\nHigh levels of CD8M cells are associated with diminished longevity in mated females (left panel; p < 0.001), but not in virgin females (center panel).Among virgin males, those dying of diseases other than the urinary syndrome MUS show no association between CD8M and longevity (open circles, upper line), but those dying because of MUS show a nonsignificant trend (filled circles, lower line, R = -0.27,p = 0.13) similar to the relationship observed in mated females.SOURCE : Miller et al. (unpublished results).Male or female mice that inherit the C57BL/6 (maternal) and C3H (paternal) alleles at D12Mit167 (light gray bars) are longer lived than their siblings that inherit the BALB plus C3H combination.The \"effect size\" shown at the right represents that difference in mean longevity between mice in the two genetically different groups, with (**) = p < 0.01 and (*) = p < 0.05 by t-test.Similar effect sizes are seen for mice dying of cancer or of non-neoplastic illnesses (\"benign\"), and among the cancer deaths the genetic effect is similar for deaths due to lymphoma and hepatoma.The genetic effect on longevity seems to be minimal, however, for mice dying of fibrosarcoma.Bars show means plus standard errors.SOURCE : Miller et al. (unpublished results)." + }, + { + "document_id": "98ce73c6-a53b-486f-8326-4b0bd47ec22e", + "text": "\n\nOur own work has taken a different tack: we have attempted to determine whether mutations with differential effects on aging may be present within the many available populations of laboratory-adopted inbred mice.The goal is not so much to clone these genes-if indeed they existbecause positional cloning strategies of this kind require many thousands of animals and would be extremely expensive using an assay, age at death, that is itself so costly.Instead, the goal has been to use gene mapping methods to test hypotheses about aging and to develop new animal models that will be useful for testing well-specified hypotheses about the molecular basis for age-dependent changes.In the absence of a validated battery of biomarkers of aging, we (like most others) have reluctantly decided to use mouse life span as a crude surrogate for aging itself, reasoning that genetic alleles that extend life span well beyond the median for the tested population may be operating via an influence on aging itself.Work conducted using recombinant inbred mouse stocks (Gelman et al., 1988;de Haan and Van Zant, 1999) has suggested that life-span differences between pairs of inbred mouse lines might reflect the influence of as few as 4-7 polymorphic loci, providing some basis for hope that some of these would have an effect large enough to be detected by a genome scan experiment involving 300-1,200 mice." + } + ], + "9ac0b7e7-6294-4cfb-97e3-e5a4546af324": [ + { + "document_id": "9ac0b7e7-6294-4cfb-97e3-e5a4546af324", + "text": ", Vogler, G.P. , Vandenbergh,\nD.J. , Blizard, D.A. , Stout, J.T. & McClearn, G.E. Quantitative Trait\nLocus (QTL) Analysis of Longevity in C57BL/6J byDBA/2J (BXD)\nRecombinant Inbred Mice. Aging Clin Exp Res (in press). Lionikas, A., Blizard, D.A. , Vandenbergh, D.J. , Glover, M.G. ,\nStout, J.T. , Vogler, G.P. , McClearn, G.E. & Larsson, L. (2003)\nGenetic architecture of fast- and slow-twitch skeletal muscle\nweight in 200-day-old mice of the C57BL/6J and DBA/2J lineage. Physiol Genomics 16, 141–152. Lionikas A., Blizard D.A. , Gerhard G.S. , Vandenbergh D.J. , Stout J.T. ,\nVogler G.P. , McClearn G.E." + } + ], + "cb3f9967-9762-4a9b-96cb-0acccdc316d2": [ + { + "document_id": "cb3f9967-9762-4a9b-96cb-0acccdc316d2", + "text": "Deficiency mapping of quantitative trait loci affecting longevity\nin Drosophila melanogaster. Genetics 2000;156:1129–1146. [PubMed: 11063689]\n33. Ma RZ, et al. Identification of Bphs, an autoimmune disease locus, as histamine receptor H1. Science\n2002;297:620–623. [PubMed: 12142541]\n\nNat Rev Genet. Author manuscript; available in PMC 2007 November 5. Page 12\n\nNIH-PA Author Manuscript\n\n34. Vivian JL, Chen Y, Yee D, Schneider E, Magnuson T. An allelic series of mutations in Smad2 and\nSmad4 identified in a genotype-based screen of N-ethyl-N-nitrosourea-mutagenized mouse\nembryonic stem cells. Proc. Natl Acad. Sci. USA 2002;99:15542–15547. [PubMed: 12432092]\n35. Vogel G. Scientists dream of 1001 complex mice." + } + ], + "ce2c68bf-878d-460c-8d9b-d45ce3034ef7": [ + { + "document_id": "ce2c68bf-878d-460c-8d9b-d45ce3034ef7", + "text": "34. Gelman R, Watson A, Bronson R & Yunis E Murine chromosomal regions correlated with\nlongevity. Genetics 118, 693–704 (1988). [PubMed: 3163317]\n35. Houtkooper RHet al.The metabolic footprint of aging in mice. Sci. Rep1, (2011). 36. Houtkooper RHet al.Mitonuclear protein imbalance as a conserved longevity mechanism. Nature497, 451–457 (2013). [PubMed: 23698443]\n37. Williams EGet al.An Evolutionarily conserved role for the aryl hydrocarbon receptor in the\nregulation of movement. PLOS Genet. 10, e1004673 (2014). [PubMed: 25255223]\n38. Lang DHet al.Quantitative trait loci (QTL) analysis of longevity in C57BL/6J by DBA/2J (BXD)\nrecombinant inbred mice. Aging Clin. Exp. Res. 22, 8–19 (2010)." + } + ], + "db0459f8-6602-48d7-be9b-14863a88bbe1": [ + { + "document_id": "db0459f8-6602-48d7-be9b-14863a88bbe1", + "text": "In addition,\nthe B6 mouse strain is one of the longest-lived mouse strains with a mean lifespan of 3\nyears versus other mouse strains with mean lifespan from 1.5-2 years. Therefore, it is\nevident that the genetic background of a particular mouse strain can have a profound\neffect on the biology of the HSC population as well as organismal longevity. Indeed, it is\nfor this reason that it is difficult to compare findings from various laboratories where\ndifferent mouse strains are used." + } + ], + "e2eaa1f2-1a1c-42b7-ab7f-e69a0394f748": [ + { + "document_id": "e2eaa1f2-1a1c-42b7-ab7f-e69a0394f748", + "text": "NIH-PA Author Manuscript\n\nThis study indicated a large amount of genetic variation for mouse longevity; heritability\nwas 34% for AL and 36% for DR (60% of AL food intake). There was no significant\ncorrelation between mean longevity under these two conditions, although maximum\nlifespans of the AL and DR mice were significantly correlated. Similar observations were\nmade at the UTHSCSA on the ILSXISS RI mice (Liao et al. , 2010a, b; Mattson 2010),\nwhere they also observed similar heritability (28% AL males, 36% AL females, 55% DR\nmales, 53% DR females)." + }, + { + "document_id": "e2eaa1f2-1a1c-42b7-ab7f-e69a0394f748", + "text": "For females, hairs of the congenic mice grew 31% faster, also highly significant (P =\n0.0006, 1-tailed). These results validated the presence of a gene in the differential region\naffecting FE. Discussion\nWe report the outcomes of a quantitative genetic study on aging and longevity in the mouse. We studied an extant series of recombinant inbred strains (ILSXISS) that have been used\nboth in DR aging studies as well as to study alcohol sensitivity (Williams et al. , 2004)." + }, + { + "document_id": "e2eaa1f2-1a1c-42b7-ab7f-e69a0394f748", + "text": "(2007) is a separate issue from the analyses conducted in this\nstudy (the AL efficiency model will be tested in future studies). Exp Gerontol. Author manuscript; available in PMC 2011 September 1. Rikke et al. Page 8\n\nNIH-PA Author Manuscript\n\nOther studies have also reported that individual mice that maintained the highest BW were\nlikely to be the longest-lived individuals among cohorts of genetically identical mice\n(Weindruch et al. , 1986; Harper et al. , 2006)." + } + ], + "f116ee1c-b275-4239-98e9-c2032b8f05c5": [ + { + "document_id": "f116ee1c-b275-4239-98e9-c2032b8f05c5", + "text": "Age-associated changes are conserved between mouse strains\n\nLife span and aging vary between mouse strains.For example, C57BL/6 mice are long-lived compared to the short-lived DBA/2 mice (Turturro et al. 1999).To test the generality of our observations, we also examined LT-HSCs, ST-HSC and MPPs in young and old mice from the DBA/2 strain, which originates from a distinct breeding lineage (Fox 1997)." + } + ] + }, + "data_source": [], + "document_id": "2D2D12594F1A6AC91E150695D70A4FFA", + "engine": "gpt-4", + "first_load": false, + "focus": "api", + "keywords": [ + "C57BL/6&allele", + "C3H&allele", + "BALB&allele", + "D2Mit58", + "D16Mit182", + "longevity", + "mouse", + "genetic", + "D12Mit167", + "IGF-1" + ], + "metadata": [], + "question": "Which mouse genes have been associated with longevity?", + "subquestions": null, + "task_id": "2D2D12594F1A6AC91E150695D70A4FFA", + "usage": { + "chatgpt": 9852, + "gpt-4": 6314, + "gpt-4-turbo-preview": 4895 + }, + "user_id": 2 + }, + "document_id": "2D2D12594F1A6AC91E150695D70A4FFA", + "task_id": "2D2D12594F1A6AC91E150695D70A4FFA" +} |