Skip to main content
SpringerLink
Log in

Genetic Markers of Extreme Human Longevity

  • Chapter
  • First Online:
Biomarkers of Human Aging

Part of the book series: Healthy Ageing and Longevity ((HAL,volume 10))

  • 1441 Accesses

Abstract

We review issues related to studying the genetics of extreme human longevity, including the definition of the phenotype, the choice of appropriate controls, the effect of population structure and assortative mating. We then discuss the important contributions to the genetics of extreme human longevity of the last few years that have arisen from genome-wide association studies and the work that is needed to discover additional longevity genes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Andersen SL, Sebastiani P, Dworkis DA, Feldman L, Perls TT (2016) Health span approximates life span among many supercentenarians: compression of morbidity at the approximate limit of life span. J Gerontol A Biol Sci Med Sci 67(4):395–405. Epub 2012/01/06. https://doi.org/10.1093/gerona/glr223. PubMed PMID: 22219514; PMCID: 3309876

    Article  Google Scholar 

  • Anselmi CV, Malovini A, Roncarati R, Novelli V, Villa F, Condorelli G, Bellazzi R, Puca AA (2009) Association of the FOXO3A locus with extreme longevity in a southern Italian centenarian study. Rejuvenation Res 12(2):95–104. Epub 2009/05/07. https://doi.org/10.1089/rej.2008.0827. PubMed PMID: 19415983

    Article  CAS  Google Scholar 

  • Atzmon G, Schechter C, Greiner W, Davidson D, Rennert G, Barzilai N (2004) Clinical phenotype of families with longevity. J Am Geriatr Soc 52(2):274–277 Epub 2004/01/20 PubMed PMID: 14728640

    Article  Google Scholar 

  • Bae H, Gurinovich A, Malovini A, Atzmon G, Andersen SL, Villa F, Barzilai N, Puca A, Perls TT, Sebastiani P (2018) Effects of FOXO3 polymorphisms on survival to extreme longevity in four centenarian studies. J Gerontol Series A, Biol Sci Med Sci 73(11):1439–1447. Epub 2017/10/05. https://doi.org/10.1093/gerona/glx124. PubMed PMID: 28977569; PMCID: 6175020

    Article  Google Scholar 

  • Bao JM, Song XL, Hong YQ, Zhu HL, Li C, Zhang T, Chen W, Zhao SC, Chen Q (2014) Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis. Asian J Androl 16(3):446–452. Epub 2014/03/05. https://doi.org/10.4103/1008-682x.123673 123673 [pii]. PubMed PMID: 24589462; PMCID: 4023376

    Article  Google Scholar 

  • Bartke A (2008) Impact of reduced insulin-like growth factor-1/insulin signaling on aging in mammals: novel findings. Aging Cell 7(3):285–290. Epub 2008/03/19. https://doi.org/10.1111/j.1474-9726.2008.00387.x ACE387 [pii]. PubMed PMID: 18346217

    Article  CAS  Google Scholar 

  • Blanche H, Cabanne L, Sahbatou M, Thomas G (2001) A study of French centenarians: are ACE and APOE associated with longevity? C R Acad Sci III 324(2):129–135. Epub 2001/03/31. doi:S0764446900012749 [pii]. PubMed PMID: 11280044

    Google Scholar 

  • Brandstrom A (1993) Infant mortality in Sweden 1750–1950. In: The decline of infant mortality in Europe 1800–1950 four national case studies. URL: http://www.unicef-ircorg/publications/pdf/hisper_decline_infantmortalitypdf. Accessed 15 Apr 2013 [Internet]. UNICEF, Florence, Italy

  • Broer L, Buchman AS, Deelen J, Evans DS, Faul JD, Lunetta KL, Sebastiani P, Smith JA, Smith AV, Tanaka T, Yu L, Arnold AM, Aspelund T, Benjamin EJ, De Jager PL, Eirkisdottir G, Evans DA, Garcia ME, Hofman A, Kaplan RC, Kardia SL, Kiel DP, Oostra BA, Orwoll ES, Parimi N, Psaty BM, Rivadeneira F, Rotter JI, Seshadri S, Singleton A, Tiemeier H, Uitterlinden AG, Zhao W, Bandinelli S, Bennett DA, Ferrucci L, Gudnason V, Harris TB, Karasik D, Launer LJ, Perls TT, Slagboom PE, Tranah GJ, Weir DR, Newman AB, van Duijn CM, Murabito JM (2015) GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy. J Gerontol A Biol Sci Med Sci 70(1):110–118. https://doi.org/10.1093/gerona/glu166 PubMed PMID: 25199915; PMCID: PMC4296168

    Article  CAS  PubMed  Google Scholar 

  • Castro E, Ogburn CE, Hunt KE, Tilvis R, Louhija J, Penttinen R, Erkkola R, Panduro A, Riestra R, Piussan C, Deeb SS, Wang L, Edland SD, Martin GM, Oshima J (1999) Polymorphisms at the Werner locus: I. Newly identified polymorphisms, ethnic variability of 1367Cys/Arg, and its stability in a population of Finnish centenarians. Am J Med Genet 82(5):399–403. Epub 1999/03/09. https://doi.org/10.1002/(sici)1096-8628(19990219)82:5%3c399::aid-ajmg8%3e3.0.co;2-r [pii]. PubMed PMID: 10069711

    Article  CAS  Google Scholar 

  • Choi YH, Kim JH, Kim DK, Kim JW, Kim DK, Lee MS, Kim CH, Park SC (2003) Distributions of ACE and APOE polymorphisms and their relations with dementia status in Korean centenarians. J Gerontol A Biol Sci Med Sci 58(3):227–231 PubMed PMID: 12634288

    Article  Google Scholar 

  • Christensen K, Johnson TE, Vaupel JW (2006) The quest for genetic determinants of human longevity: challenges and insights. Nat Rev Genet 7(6):436–448 PubMed PMID: 16708071

    Article  CAS  Google Scholar 

  • Clancy DJ, Gems D, Harshman LG, Oldham S, Stocker H, Hafen E, Leevers SJ, Partridge L (2001) Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science 292(5514):104–106. Epub 2001/04/09. https://doi.org/10.1126/science.1057991 292/5514/104 [pii]. PubMed PMID: 11292874

    Article  CAS  Google Scholar 

  • Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261(5123):921–923 Epub 1993/08/13 PubMed PMID: 8346443

    Article  CAS  Google Scholar 

  • Deelen J, Beekman M, Uh HW, Helmer Q, Kuningas M, Christiansen L, Kremer D, van der Breggen R, Suchiman HE, Lakenberg N, van den Akker EB, Passtoors WM, Tiemeier H, van Heemst D, de Craen AJ, Rivadeneira F, de Geus EJ, Perola M, van der Ouderaa FJ, Gunn DA, Boomsma DI, Uitterlinden AG, Christensen K, van Duijn CM, Heijmans BT, Houwing-Duistermaat JJ, Westendorp RG, Slagboom PE (2011) Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited. Aging Cell 10(4):686–698. Epub 2011/03/23. https://doi.org/10.1111/j.1474-9726.2011.00705.x. PubMed PMID: 21418511

    Article  CAS  Google Scholar 

  • Deelen J, Beekman M, Uh HW, Broer L, Ayers KL, Tan Q, Kamatani Y, Bennet AM, Tamm R, Trompet S, Guethbjartsson DF, Flachsbart F, Rose G, Viktorin A, Fischer K, Nygaard M, Cordell HJ, Crocco P, van den Akker EB, Bohringer S, Helmer Q, Nelson CP, Saunders GI, Alver M, Andersen-Ranberg K, Breen ME, van der Breggen R, Caliebe A, Capri M, Cevenini E, Collerton JC, Dato S, Davies K, Ford I, Gampe J, Garagnani P, de Geus EJ, Harrow J, van Heemst D, Heijmans BT, Heinsen FA, Hottenga JJ, Hofman A, Jeune B, Jonsson PV, Lathrop M, Lechner D, Martin-Ruiz C, McNerlan SE, Mihailov E, Montesanto A, Mooijaart SP, Murphy A, Nohr EA, Paternoster L, Postmus I, Rivadeneira F, Ross OA, Salvioli S, Sattar N, Schreiber S, Stefansson H, Stott DJ, Tiemeier H, Uitterlinden AG, Westendorp RG, Willemsen G, Samani NJ, Galan P, Sorensen TI, Boomsma DI, Jukema JW, Rea IM, Passarino G, de Craen AJ, Christensen K, Nebel A, Stefansson K, Metspalu A, Magnusson P, Blanche H, Christiansen L, Kirkwood TB, van Duijn CM, Franceschi C, Houwing-Duistermaat JJ, Slagboom PE (2014) Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age. Hum Mol Genet 23(16):4420–4432. https://doi.org/10.1093/hmg/ddu139 PubMed PMID: 24688116; PMCID: 4103672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Epstein MP, Allen AS, Satten GA (2007) A simple and improved correction for population stratification in case-control studies. Am J Hum Genet 80(5):921–930. Epub 2007/04/17. https://doi.org/10.1086/516842. PubMed PMID: 17436246; PMCID: PMC1852732

    Article  CAS  Google Scholar 

  • Evangelou E, Ioannidis JP (2013) Meta-analysis methods for genome-wide association studies and beyond. Nat Rev Genet 14(6):379–389. Epub 2013/05/10. https://doi.org/10.1038/nrg3472. PubMed PMID: 23657481

    Article  CAS  Google Scholar 

  • Feng J, Xiang L, Wan G, Qi K, Sun L, Huang Z, Zheng C, Lv Z, Hu C, Yang Z (2011) Is APOE epsilon3 a favourable factor for the longevity: an association study in Chinese population. J Genet 90(2):343–347 Epub 2011/08/27 PubMed PMID: 21869487

    Article  Google Scholar 

  • Flachsbart F, Caliebe A, Kleindorp R, Blanche H, von Eller-Eberstein H, Nikolaus S, Schreiber S, Nebel A (2009) Association of FOXO3A variation with human longevity confirmed in German centenarians. Proc Natl Acad Sci USA 106(8):2700–2705. Epub 2009/02/07. https://doi.org/10.1073/pnas.0809594106 0809594106 [pii]. PubMed PMID: 19196970; PMCID: 2650329

    Article  CAS  Google Scholar 

  • Freudenberg-Hua Y, Freudenberg J, Vacic V, Abhyankar A, Emde AK, Ben-Avraham D, Barzilai N, Oschwald D, Christen E, Koppel J, Greenwald B, Darnell RB, Germer S, Atzmon G, Davies P (2014) Disease variants in genomes of 44 centenarians. Mol Genet Genomic Med 2:438–450

    Article  CAS  Google Scholar 

  • Garatachea N, Emanuele E, Calero M, Fuku N, Arai Y, Abe Y, Murakami H, Miyachi M, Yvert T, Verde Z, Zea MA, Venturini L, Santiago C, Santos-Lozano A, Rodriguez-Romo G, Ricevuti G, Hirose N, Rabano A, Lucia A (2014) ApoE gene and exceptional longevity: insights from three independent cohorts. Exp Gerontol 53:16–23. Epub 2014/02/19. https://doi.org/10.1016/j.exger.2014.02.004. PubMed PMID: 24534555

    Article  CAS  Google Scholar 

  • Garatachea N, Marin PJ, Santos-Lozano A, Sanchis-Gomar F, Emanuele E, Lucia A (2015) The ApoE gene is related with exceptional longevity: a systematic review and meta-analysis. Rejuvenation Res 18(1):3–13. Epub 2014/11/12. https://doi.org/10.1089/rej.2014.1605. PubMed PMID: 25385258

    Article  CAS  Google Scholar 

  • Gerdes LU, Jeune B, Ranberg KA, Nybo H, Vaupel JW (2000) Estimation of apolipoprotein E genotype-specific relative mortality risks from the distribution of genotypes in centenarians and middle-aged men: apolipoprotein E gene is a “frailty gene,” not a “longevity gene”. Genet Epidemiol 19(3):202–210. Epub 2000/10/03. https://doi.org/10.1002/1098-2272(200010)19:3%3c202::aid-gepi2%3e3.0.co;2-q. PubMed PMID: 11015124

    Article  CAS  Google Scholar 

  • Gierman HJ, Fortney K, Roach JC, Coles NS, Li H, Glusman G, Markov GJ, Smith JD, Hood L, Coles LS, Kim SK (2014) Whole-genome sequencing of the world’s oldest people. PLoS One 9(11):e112430. Epub 2014/11/13. https://doi.org/10.1371/journal.pone.0112430. PubMed PMID: 25390934; PMCID: 4229186

    Article  Google Scholar 

  • Giuliani C, Sazzini M, Pirazzini C, Bacalini MG, Marasco E, Ruscone GAG, Fang F, Sarno S, Gentilini D, Di Blasio AM, Crocco P, Passarino G, Mari D, Monti D, Nacmias B, Sorbi S, Salvarani C, Catanoso M, Pettener D, Luiselli D, Ukraintseva S, Yashin A, Franceschi C, Garagnani P (2018) Impact of demography and population dynamics on the genetic architecture of human longevity. Aging (Albany NY). 10(8):1947–63. https://doi.org/10.18632/aging.101515. PubMed PMID: 30089705; PMCID: PMC6128422

    Article  Google Scholar 

  • Giuliani C, Garagnani P, Franceschi C (2018b) Genetics of human longevity within an eco-evolutionary nature-nurture framework. Circ Res 123(7):745–772. https://doi.org/10.1161/CIRCRESAHA.118.312562 PubMed PMID: 30355083

    Article  CAS  PubMed  Google Scholar 

  • Guan W, Liang L, Boehnke M, Abecasis GR (2009) Genotype-based matching to correct for population stratification in large-scale case-control genetic association studies. Genet Epidemiol 33(6):508–517. Epub 2009/01/27. https://doi.org/10.1002/gepi.20403. PubMed PMID: 19170134; PMCID: PMC2732762

    Article  Google Scholar 

  • Hapi Heart: Genome-wide Search for CVD Gene-Environment. Available from: https://dsgweb.wustl.edu/progeni/studies/hapiheart.html

  • He YH, Lu X, Yang LQ, Xu LY, Kong QP (2014) Association of the insulin-like growth factor binding protein 3 (IGFBP-3) polymorphism with longevity in Chinese nonagenarians and centenarians. Aging (Albany NY) 6(11):944–956. Epub 2015/01/03. doi:100703 [pii]. PubMed PMID: 25553725; PMCID: 4276788

    Google Scholar 

  • Hinds DA, Stokowski RP, Patil N, Konvicka K, Kershenobich D, Cox DR, Ballinger DG (2004) Matching strategies for genetic association studies in structured populations. Am J Hum Genet 74(2):317–325. Epub 2004/01/24. doi:AJHG40522 [pii]. PubMed PMID: 14740319; PMCID: 1181929

    Google Scholar 

  • Hitt R, Young-Xu Y, Silver M, Perls T (1999) Centenarians: the older you get, the healthier you have been. Lancet 354(9179):652. Epub 1999/08/31. doi:S0140-6736(99)01987-X [pii] https://doi.org/10.1016/s0140-6736(99)01987-x. PubMed PMID: 10466675

  • Joshi PK, Fischer K, Schraut KE, Campbell H, Esko T, Wilson JF (2016) Variants near CHRNA3/5 and APOE have age- and sex-related effects on human lifespan. Nat Commun 7:11174. https://doi.org/10.1038/ncomms11174 PubMed PMID: 27029810; PMCID: PMC5438072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Joshi PK, Pirastu N, Kentistou KA, Fischer K, Hofer E, Schraut KE, Clark DW, Nutile T, Barnes CLK, Timmers P, Shen X, Gandin I, McDaid AF, Hansen TF, Gordon SD, Giulianini F, Boutin TS, Abdellaoui A, Zhao W, Medina-Gomez C, Bartz TM, Trompet S, Lange LA, Raffield L, van der Spek A, Galesloot TE, Proitsi P, Yanek LR, Bielak LF, Payton A, Murgia F, Concas MP, Biino G, Tajuddin SM, Seppala I, Amin N, Boerwinkle E, Borglum AD, Campbell A, Demerath EW, Demuth I, Faul JD, Ford I, Gialluisi A, Gogele M, Graff M, Hingorani A, Hottenga JJ, Hougaard DM, Hurme MA, Ikram MA, Jylha M, Kuh D, Ligthart L, Lill CM, Lindenberger U, Lumley T, Magi R, Marques-Vidal P, Medland SE, Milani L, Nagy R, Ollier WER, Peyser PA, Pramstaller PP, Ridker PM, Rivadeneira F, Ruggiero D, Saba Y, Schmidt R, Schmidt H, Slagboom PE, Smith BH, Smith JA, Sotoodehnia N, Steinhagen-Thiessen E, van Rooij FJA, Verbeek AL, Vermeulen SH, Vollenweider P, Wang Y, Werge T, Whitfield JB, Zonderman AB, Lehtimaki T, Evans MK, Pirastu M, Fuchsberger C, Bertram L, Pendleton N, Kardia SLR, Ciullo M, Becker DM, Wong A, Psaty BM, van Duijn CM, Wilson JG, Jukema JW, Kiemeney L, Uitterlinden AG, Franceschini N, North KE, Weir DR, Metspalu A, Boomsma DI, Hayward C, Chasman D, Martin NG, Sattar N, Campbell H, Esko T, Kutalik Z, Wilson JF (2017) Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity. Nat Commun 8(1):910. https://doi.org/10.1038/s41467-017-00934-5 PubMed PMID: 29030599; PMCID: PMC5715013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366(6454):461–464. Epub 1993/12/02. https://doi.org/10.1038/366461a0. PubMed PMID: 8247153

    Article  CAS  Google Scholar 

  • Kimmel G, Jordan MI, Halperin E, Shamir R, Karp RM (2007) A randomization test for controlling population stratification in whole-genome association studies. Am J Hum Genet 81(5):895–905. Epub 2007/10/10. https://doi.org/10.1086/521372. PubMed PMID: 17924333; PMCID: PMC2265648

    Article  CAS  Google Scholar 

  • Li Y, Wang WJ, Cao H, Lu J, Wu C, Hu FY, Guo J, Zhao L, Yang F, Zhang YX, Li W, Zheng GY, Cui H, Chen X, Zhu Z, He H, Dong B, Mo X, Zeng Y, Tian XL (2009) Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations. Hum Mol Genet 18(24):4897–4904. Epub 2009/10/02. https://doi.org/10.1093/hmg/ddp459 ddp459 [pii]. PubMed PMID: 19793722; PMCID: 2790334

    Article  CAS  Google Scholar 

  • Louhija J, Miettinen HE, Kontula K, Tikkanen MJ, Miettinen TA, Tilvis RS (1994) Aging and genetic variation of plasma apolipoproteins. Relative loss of the apolipoprotein E4 phenotype in centenarians. Arterioscler Thromb 14(7):1084–1089. Epub 1994/07/01. PubMed PMID: 8018664

    Article  CAS  Google Scholar 

  • Luca D, Ringquist S, Klei L, Lee AB, Gieger C, Wichmann HE, Schreiber S, Krawczak M, Lu Y, Styche A, Devlin B, Roeder K, Trucco M (2008) On the use of general control samples for genome-wide association studies: genetic matching highlights causal variants. Am J Hum Genet 82(2):453–63. Epub 2008/02/07. https://doi.org/10.1016/j.ajhg.2007.11.003. PubMed PMID: 18252225; PMCID: PMC2427172

    Article  CAS  Google Scholar 

  • Malovini A, Illario M, Iaccarino G, Villa F, Ferrario A, Roncarati R, Anselmi CV, Novelli V, Cipolletta E, Leggiero E, Orro A, Rusciano MR, Milanesi L, Maione AS, Condorelli G, Bellazzi R, Puca AA (2011) Association study on long-living individuals from Southern Italy identifies rs10491334 in the CAMKIV gene that regulates survival proteins. Rejuvenation Res 14(3):283–291. Epub 2011/05/27. https://doi.org/10.1089/rej.2010.1114. PubMed PMID: 21612516

    Article  CAS  Google Scholar 

  • Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, McCarthy MI, Ramos EM, Cardon LR, Chakravarti A, Cho JH, Guttmacher AE, Kong A, Kruglyak L, Mardis E, Rotimi CN, Slatkin M, Valle D, Whittemore AS, Boehnke M, Clark AG, Eichler EE, Gibson G, Haines JL, Mackay TF, McCarroll SA, Visscher PM (2009) Finding the missing heritability of complex diseases. Nature 461(7265):747–753. Epub 2009/10/09. https://doi.org/10.1038/nature08494. PubMed PMID: 19812666; PMCID: 2831613

    Article  CAS  Google Scholar 

  • Morris BJ, Willcox DC, Donlon TA, Willcox BJ (2015) FOXO3: a major gene for human longevity—a mini-review. Gerontology 61(6):515–525. Epub 2015/04/03. https://doi.org/10.1159/000375235 000375235 [pii]. PubMed PMID: 25832544

  • Nebel A, Kleindorp R, Caliebe A, Nothnagel M, Blanche H, Junge O, Wittig M, Ellinghaus D, Flachsbart F, Wichmann HE, Meitinger T, Nikolaus S, Franke A, Krawczak M, Lathrop M, Schreiber S (2011) A genome-wide association study confirms APOE as the major gene influencing survival in long-lived individuals. Mech Ageing Dev 132(6–7):324–330. Epub 2011/07/12. https://doi.org/10.1016/j.mad.2011.06.008. PubMed PMID: 21740922

    Article  CAS  Google Scholar 

  • Newman AB, Murabito JM (2013) The epidemiology of longevity and exceptional survival. Epidemiol Rev 35:181–197. Epub 2013/02/02. https://doi.org/10.1093/epirev/mxs013. PubMed PMID: 23372024; PMCID: 4707876

    Article  Google Scholar 

  • Newman AB, Walter S, Lunetta KL, Garcia ME, Slagboom PE, Christensen K, Arnold AM, Aspelund T, Aulchenko YS, Benjamin EJ, Christiansen L, D’Agostino RB, Sr., Fitzpatrick AL, Franceschini N, Glazer NL, Gudnason V, Hofman A, Kaplan R, Karasik D, Kelly-Hayes M, Kiel DP, Launer LJ, Marciante KD, Massaro JM, Miljkovic I, Nalls MA, Hernandez D, Psaty BM, Rivadeneira F, Rotter J, Seshadri S, Smith AV, Taylor KD, Tiemeier H, Uh HW, Uitterlinden AG, Vaupel JW, Walston J, Westendorp RG, Harris TB, Lumley T, van Duijn CM, Murabito JM (2010) A meta-analysis of four genome-wide association studies of survival to age 90 years or older: the cohorts for heart and aging research in Genomic Epidemiology Consortium. J Gerontol A Biol Sci Med Sci. 65(5):478–487. Epub 2010/03/23. doi:093/gerona/glq028. PubMed PMID: 20304771; PMCID: 2854887

    Google Scholar 

  • Newman AB, Glynn NW, Taylor CA, Sebastiani P, Perls TT, Mayeux R, Christensen K, Zmuda JM, Barral S, Lee JH, Simonsick EM, Walston JD, Yashin AI, Hadley E (2011) Health and function of participants in the Long Life Family Study: a comparison with other cohorts. Aging (Albany NY) 3(1):63–76. Epub 2011/01/25. https://doi.org/10.18632/aging.100242. PubMed PMID: 21258136; PMCID: 3047140

    Article  Google Scholar 

  • Novelli V, Viviani Anselmi C, Roncarati R, Guffanti G, Malovini A, Piluso G, Puca AA (2008) Lack of replication of genetic associations with human longevity. Biogerontology 9(2):85–92. Epub 2007/11/24. https://doi.org/10.1007/s10522-007-9116-4. PubMed PMID: 18034366

    Article  Google Scholar 

  • Panza F, Solfrizzi V, Torres F, Mastroianni F, Del Parigi A, Colacicco AM, Basile AM, Capurso C, Noya R, Capurso A (1999) Decreased frequency of apolipoprotein E epsilon4 allele from Northern to Southern Europe in Alzheimer’s disease patients and centenarians. Neurosci Lett 277(1):53–56. Epub 2000/01/22. doi:S0304-3940(99)00860-5 [pii]. PubMed PMID: 10643896

    Google Scholar 

  • Pawlikowska L, Hu D, Huntsman S, Sung A, Chu C, Chen J, Joyner AH, Schork NJ, Hsueh WC, Reiner AP, Psaty BM, Atzmon G, Barzilai N, Cummings SR, Browner WS, Kwok PY, Ziv E (2009) Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity. Aging Cell 8(4):460–472. Epub 2009/06/06. doi:ACE493 [pii] https://doi.org/10.1111/j.1474-9726.2009.00493.x. PubMed PMID: 19489743

  • Pedersen JK, Elo IT, Schupf N, Perls TT, Stallard E, Yashin AI, Christensen K (2017) The survival of spouses marrying into longevity-enriched families. J Gerontol A Biol Sci Med Sci 72(1):109–114. https://doi.org/10.1093/gerona/glw159 PubMed PMID: 27540092; PMCID: PMC5155661

    Article  PubMed  Google Scholar 

  • Perls TT, Bubrick E, Wager CG, Vijg J, Kruglyak L (1998) Siblings of centenarians live longer. Lancet 351(9115):1560. Epub 1999/05/18. doi:S0140-6736(05)61126-9 PubMed PMID: 10326548

    Google Scholar 

  • Perls T, Shea-Drinkwater M, Bowen-Flynn J, Ridge SB, Kang S, Joyce E, Daly M, Brewster SJ, Kunkel L, Puca AA (2000) Exceptional familial clustering for extreme longevity in humans. J Am Geriatr Soc 48(11):1483–1485 Epub 2000/11/18 PubMed PMID: 11083328

    Article  CAS  Google Scholar 

  • Perls TT, Wilmoth J, Levenson R, Drinkwater M, Cohen M, Bogan H, Joyce E, Brewster S, Kunkel L, Puca A (2002) Life-long sustained mortality advantage of siblings of centenarians. Proc Natl Acad Sci USA 99(12):8442–8447. Epub 2002/06/13. https://doi.org/10.1073/pnas.122587599. PubMed PMID: 12060785; PMCID: 123086

    Article  CAS  Google Scholar 

  • Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38(8):904–909 PubMed PMID: 16862161

    Article  CAS  Google Scholar 

  • Price AL, Butler J, Patterson N, Capelli C, Pascali VL, Scarnicci F, Ruiz-Linares A, Groop L, Saetta AA, Korkolopoulou P, Seligsohn U, Waliszewska A, Schirmer C, Ardlie K, Ramos A, Nemesh J, Arbeitman L, Goldstein DB, Reich D, Hirschhorn JN (2008) Discerning the ancestry of European Americans in genetic association studies. PLoS Genet 4(1):e236. Epub 2008/01/23. doi:07-PLGE-RA-0516 [pii]. PubMed PMID: 18208327; PMCID: 2211542

    Google Scholar 

  • Reich D, Price AL, Patterson N (2008) Principal component analysis of genetic data. Nat Genet 40(5):491–492. Epub 2008/04/30. doi:ng0508-491 [pii]. PubMed PMID: 18443580

    Google Scholar 

  • Ruby JG, Wright KM, Rand KA, Kermany A, Noto K, Curtis D, Varner N, Garrigan D, Slinkov D, Dorfman I, Granka JM, Byrnes J, Myres N, Ball C (2018) Estimates of the heritability of human longevity are substantially inflated due to assortative mating. Genetics 210(3):1109–1124. https://doi.org/10.1534/genetics.118.301613. PubMed PMID: 30401766; PMCID: PMC6218226

    Article  Google Scholar 

  • Schachter F, Faure-Delanef L, Guenot F, Rouger H, Froguel P, Lesueur-Ginot L, Cohen D (1994) Genetic associations with human longevity at the APOE and ACE loci. Nat Genet 6(1):29–32 PubMed PMID: 8136829

    Article  CAS  Google Scholar 

  • Schupf N, Barral S, Perls T, Newman A, Christensen K, Thyagarajan B, Province M, Rossi WK, Mayeux R (2013) Apolipoprotein E and familial longevity. Neurobiol Aging 34(4):1287–1291. Epub 2012/10/09. https://doi.org/10.1016/j.neurobiolaging.2012.08.019. PubMed PMID: 23040522; PMCID: 3545094

    Article  CAS  Google Scholar 

  • Sebastiani P, Palmer LJ (2017) Human genome project. Statistics Reference Online, Wiley StatsRef

    Google Scholar 

  • Sebastiani P, Perls TT (2012) The genetics of extreme longevity: lessons from the New England centenarian study. Front Genet 3:277. Epub 2012/12/12. https://doi.org/10.3389/fgene.2012.00277. PubMed PMID: 23226160; PMCID: 3510428

  • Sebastiani P, Timofeev N, Dworkis DA, Perls TT, Steinberg MH (2009) Genome-wide association studies and the genetic dissection of complex traits. Am J Hematol 84(8):504–515. Epub 2009/07/02. https://doi.org/10.1002/ajh.21440. PubMed PMID: 19569043; PMCID: PMC Journal - In Process

    Article  CAS  Google Scholar 

  • Sebastiani P, Solovieff N, Dewan AT, Walsh KM, Puca A, Hartley SW, Melista E, Andersen S, Dworkis DA, Wilk JB, Myers RH, Steinberg MH, Montano M, Baldwin CT, Hoh J, Perls TT (2012a) Genetic signatures of exceptional longevity in humans. PLoS ONE 7(1):e29848. https://doi.org/10.1371/journal.pone.0029848 PubMed PMID: 22279548; PMCID: PMC3261167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sebastiani P, Riva A, Montano M, Pham P, Torkamani A, Scherba E, Benson G, Milton JN, Baldwin CT, Andersen S, Schork NJ, Steinberg MH, Perls TT (2012a) Whole genome sequences of a male and female supercentenarian, ages greater than 114 years. Front Genet 2:90. Epub 2012/02/04. https://doi.org/10.3389/fgene.2011.00090. PubMed PMID: 22303384; PMCID: 3262222

  • Sebastiani P, Sun FX, Andersen SL, Lee JH, Wojczynski MK, Sanders JL, Yashin A, Newman AB, Perls TT (2013) Families enriched for exceptional longevity also have increased health-span: findings from the long life family study. Front Public Health 1:38. https://doi.org/10.3389/fpubh.2013.00038 PubMed PMID: 24350207; PMCID: PMC3859985

    Article  PubMed  PubMed Central  Google Scholar 

  • Sebastiani P, Nussbaum L, Andersen SL, Black MJ, Perls TT (2016) Increasing sibling relative risk of survival to older and older ages and the importance of precise definitions of “aging,” “life span,” and “longevity”. J Gerontol A Biol Sci Med Sci 71(3):340–346. https://doi.org/10.1093/gerona/glv020.PubMedPMID:25814633;PMCID:PMC4757962

    Article  PubMed  Google Scholar 

  • Sebastiani P, Bae H, Gurinovich A, Soerensen M, Puca A, Perls TT (2017a) Limitations and risks of meta-analyses of longevity studies. Mech Ageing Dev 165(Pt B):139–146. https://doi.org/10.1016/j.mad.2017.01.008. PubMed PMID: 28143747; PMCID: PMC5533653

    Article  Google Scholar 

  • Sebastiani P, Gurinovich A, Bae H, Andersen S, Malovini A, Atzmon G, Villa F, Kraja AT, Ben-Avraham D, Barzilai N, Puca A, Perls TT (2017b) Four genome-wide association studies identify new extreme longevity variants. J Gerontol A Biol Sci Med Sci 72(11):1453–1464. https://doi.org/10.1093/gerona/glx027 PubMed PMID: 28329165; PMCID: In progress

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sebastiani P, Gurinovich A, Bae H, Andersen SL, Perls TT (2017c) Assortative mating by ethnicity in longevous families. Front Genet 8(186):186. https://doi.org/10.3389/fgene.2017.00186 PubMed PMID: 29209360; PMCID: PMC5702482

    Article  PubMed  PubMed Central  Google Scholar 

  • Sebastiani P, Gurinovich A, Nygaard M, Sasaki T, Sweigart B, Bae H, Andersen SL, Villa F, Atzmon G, Christensen K, Arai Y, Barzilai N, Puca A, Christiansen L, Hirose N, Perls TT (2018) APOE alleles and extreme human longevity. J Gerontol A Biol Sci Med Sci. https://doi.org/10.1093/gerona/gly174. PubMed PMID: 30060062

    Article  Google Scholar 

  • Sebro R, Peloso GM, Dupuis J, Risch NJ (2017) Structured mating: patterns and implications. PLoS Genet 13(4):e1006655. https://doi.org/10.1371/journal.pgen.1006655 PubMed PMID: 28384154; PMCID: PMC5383016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soerensen M, Dato S, Christensen K, McGue M, Stevnsner T, Bohr VA, Christiansen L (2010) Replication of an association of variation in the FOXO3A gene with human longevity using both case-control and longitudinal data. Aging Cell 9(6):1010–1017. Epub 2010/09/21. https://doi.org/10.1111/j.1474-9726.2010.00627.x. PubMed PMID: 20849522; PMCID: 2992870

    Article  CAS  Google Scholar 

  • Solovieff N, Hartley SW, Baldwin CT, Perls TT, Steinberg MH, Sebastiani P (2010) Clustering by genetic ancestry using genome-wide SNP data. BMC Genet 11:108. Epub 2010/12/15. https://doi.org/10.1186/1471-2156-11-108. PubMed PMID: 21143920; PMCID: 3018397

    Article  Google Scholar 

  • Stakias N, Liakos P, Tsiapali E, Goutou M, Koukoulis GN (2006) Lower prevalence of epsilon 4 allele of apolipoprotein E gene in healthy, longer-lived individuals of Hellenic origin. J Gerontol A Biol Sci Med Sci 61(12):1228–1231. Epub 2007/01/20. doi:61/12/1228 [pii]. PubMed PMID: 17234815

    Google Scholar 

  • Stevenson M, Bae H, Schupf N, Andersen S, Zhang Q, Perls T, Sebastiani P (2015) Burden of disease variants in participants of the Long Life Family Study. Aging (Albany NY) 7(2):123–132. https://doi.org/10.18632/aging.100724 PubMed PMID: 25664523; PMCID: PMC4359694

    Article  CAS  Google Scholar 

  • Sun L, Hu C, Zheng C, Qian Y, Liang Q, Lv Z, Huang Z, Qi K, Gong H, Zhang Z, Huang J, Zhou Q, Yang Z (2015) FOXO3 variants are beneficial for longevity in Southern Chinese living in the Red River Basin: a case-control study and meta-analysis. Sci Rep 5:9852. Epub 2015/04/29. https://doi.org/10.1038/srep09852 srep09852 [pii]. PubMed PMID: 25913413

  • Terry DF, Sebastiani P, Andersen SL, Perls TT (2008) Disentangling the roles of disability and morbidity in survival to exceptional old age. Arch Intern Med 168(3):277–283. Epub 2008/02/13. doi:168/3/277 [pii] https://doi.org/10.1001/archinternmed.2007.75. PubMed PMID: 18268168; PMCID: http://archinte.ama-assn.org/cgi/content/full/168/3/277

  • Tian C, Kosoy R, Nassir R, Lee A, Villoslada P, Klareskog L, Hammarstrom L, Garchon HJ, Pulver AE, Ransom M, Gregersen PK, Seldin MF (2009) European population genetic substructure: further definition of ancestry informative markers for distinguishing among diverse European ethnic groups. Mol Med 15(11–12):371–383. https://doi.org/10.2119/molmed.2009.00094 PubMed PMID: 19707526; PMCID: PMC2730349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Visscher PM, Wray NR, Zhang Q, Sklar P, McCarthy MI, Brown MA, Yang J (2017) 10 years of GWAS discovery: biology, function, and translation. Am J Hum Genet 101(1):5–22. https://doi.org/10.1016/j.ajhg.2017.06.005 PubMed PMID: 28686856; PMCID: PMC5501872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walter S, Atzmon G, Demerath EW, Garcia ME, Kaplan RC, Kumari M, Lunetta KL, Milaneschi Y, Tanaka T, Tranah GJ, Volker U, Yu L, Arnold A, Benjamin EJ, Biffar R, Buchman AS, Boerwinkle E, Couper D, De Jager PL, Evans DA, Harris TB, Hoffmann W, Hofman A, Karasik D, Kiel DP, Kocher T, Kuningas M, Launer LJ, Lohman KK, Lutsey PL, Mackenbach J, Marciante K, Psaty BM, Reiman EM, Rotter JI, Seshadri S, Shardell MD, Smith AV, van Duijn C, Walston J, Zillikens MC, Bandinelli S, Baumeister SE, Bennett DA, Ferrucci L, Gudnason V, Kivimaki M, Liu Y, Murabito JM, Newman AB, Tiemeier H, Franceschini N (2011) A genome-wide association study of aging. Neurobiol Aging 32(11):e15–e28. Epub 2011/07/26. https://doi.org/10.1016/j.neurobiolaging.2011.05.026. PubMed PMID: 21782286; PMCID: 3193030

    Article  Google Scholar 

  • Wang K (2009) Testing for genetic association in the presence of population stratification in genome-wide association studies. Genet Epidemiol 33(7):637–645. Epub 2009/02/24. https://doi.org/10.1002/gepi.20415. PubMed PMID: 19235185

    Article  Google Scholar 

  • Willcox BJ, Donlon TA, He Q, Chen R, Grove JS, Yano K, Masaki KH, Willcox DC, Rodriguez B, Curb JD (2008) FOXO3A genotype is strongly associated with human longevity. Proc Natl Acad Sci USA 105(37):13987–13992. Epub 2008/09/04. doi:0801030105 [pii] https://doi.org/10.1073/pnas.0801030105. PubMed PMID: 18765803

  • Yip AG, McKee AC, Green RC, Wells J, Young H, Cupples LA, Farrer LA (2005) APOE, vascular pathology, and the AD brain. Neurology 65(2):259–265. https://doi.org/10.1212/01.wnl.0000168863.49053.4d PubMed PMID: 16043796

    Article  CAS  PubMed  Google Scholar 

  • Zeng Y, Nie C, Min J, Liu X, Li M, Chen H, Xu H, Wang M, Ni T, Li Y, Yan H, Zhang JP, Song C, Chi LQ, Wang HM, Dong J, Zheng GY, Lin L, Qian F, Qi Y, Cao H, Wang Y, Zhang L, Li Z, Zhou Y, Lu J, Li J, Qi M, Bolund L, Yashin A, Land KC, Gregory S, Yang Z, Gottschalk W, Tao W, Wang J, Xu X, Bae H, Nygaard M, Christiansen L, Christensen K, Franceschi C, Lutz MW, Gu J, Tan Q, Perls T, Sebastiani P, Deelen J, Slagboom E, Hauser E, Tian XL, Yang H, Vaupel JW (2016) Novel loci and pathways significantly associated with longevity. Sci Rep 6:21243. Epub 2016/02/26. https://doi.org/10.1038/srep21243. PubMed PMID: 26912274; PMCID: 4766491

Download references

Funding

This work was supported by the National Institute on Aging (U19AG023122, R21AG056630 and R01AG061844).

Author information

Authors and Affiliations

  1. Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue, Boston, MA, 02118, USA

    Paola Sebastiani & Anastasia Gurinovich

  2. College of Public Health and Human Sciences, Oregon State University, 2520 SW Campus Way, Corvallis, OR, 97331, USA

    Harold Bae

  3. Department of Medicine, Geriatric, Boston University School of Medicine and Boston Medical Center, Robinson 2400, 88 E Newton St., Boston, MA, 02118, USA

    Thomas T. Perls

Authors
  1. Paola Sebastiani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anastasia Gurinovich
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Harold Bae
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thomas T. Perls
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paola Sebastiani .

Editor information

Editors and Affiliations

  1. Laboratory of Geroprotective and Radioprotective Technologies, Institute of Biology, Komi Science Center of RAS, Syktyvkar, Komi Republic, Russia

    Alexey Moskalev

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Sebastiani, P., Gurinovich, A., Bae, H., Perls, T.T. (2019). Genetic Markers of Extreme Human Longevity. In: Moskalev, A. (eds) Biomarkers of Human Aging. Healthy Ageing and Longevity, vol 10. Springer, Cham. https://doi.org/10.1007/978-3-030-24970-0_10

Download citation

Publish with us

Policies and ethics

Search

Navigation