Genetic Signatures of Centenarians: Implications for Achieving Successful Aging

Author(s): Calogero Caruso, Anna Aiello, Giulia Accardi, Elena Ciaglia, Monica Cattaneo, Annibale Puca*.

Journal Name: Current Pharmaceutical Design

Volume 25 , Issue 39 , 2019

Become EABM
Become Reviewer

Abstract:

The extraordinary rise in the old population in the Western world underscores the importance of studies on aging and longevity to decrease the medical, economic and social problems associated with the increased number of non-autonomous individuals affected by invalidating pathologies. Centenarians have reached the extreme limits of the human life span. They are the best example of extreme longevity, representing selected individuals in which the appearance of major age-related diseases has been consistently delayed or avoided. There is growing evidence that the genetic component of longevity becomes higher with survival at the age of over 90 years. For centenaries, it reaches up to 33% for women and 48% for men. Therefore, exceptional longevity is a complex, hereditable trait that runs across generations. Longevity should correlate either with the presence of protective alleles or the absence of detrimental alleles. The aim of this review is to discuss the possible attainment of successful aging in the context of the lessons learned from centenarian genetics.

Keywords: Cardiovascular diseases, centenarians, genetics, immune-inflammatory responses, longevity, successful aging.

[1]
Accardi G, Aiello A, Vasto S, et al. Chance and causality in ageing and longevity. In: Caruso C, Ed., Centenarians. An Example of Positive Biology. Switzerland: Springer. 2019; 1-21.
[http://dx.doi.org/10.1007/978-3-030-20762-5_1]
[2]
Lutz W, Kebede E. Education and health: redrawing the Preston curve. Popul Dev Rev 2018; 44(2): 343-61.
[http://dx.doi.org/10.1111/padr.12141] [PMID: 29937609]
[3]
Kirkwood TB. Systems biology of ageing and longevity. Philos Trans R Soc Lond B Biol Sci 2011; 366(1561): 64-70.
[http://dx.doi.org/10.1098/rstb.2010.0275] [PMID: 21115531]
[4]
Troen BR. The biology of aging. Mt Sinai J Med 2003; 70(1): 3-22.
[PMID: 12516005]
[5]
Seals DR, Melov S. Translational geroscience: emphasizing function to achieve optimal longevity. Aging (Albany NY) 2014; 6(9): 718-30.
[http://dx.doi.org/10.18632/aging.100694] [PMID: 25324468]
[6]
Aiello A, Ligotti ME, Cossarizza A. Centenarian Offspring as a Model of Successful Ageing. In: Caruso C, Ed., Centenarians. An Example of Positive Biology. Switzerland: Springer 2019; 35-51.
[http://dx.doi.org/10.1007/978-3-030-20762-5_3]
[7]
Avery P, Barzilai N, Benetos A, et al. Ageing, longevity, exceptional longevity and related genetic and non genetics markers: panel statement. Curr Vasc Pharmacol 2014; 12(5): 659-61.
[http://dx.doi.org/10.2174/1570161111666131219101226] [PMID: 24350929]
[8]
Kolovou G, Barzilai N, Caruso C, et al. The challenges in moving from ageing to successful longevity. Curr Vasc Pharmacol 2014; 12(5): 662-73.
[http://dx.doi.org/10.2174/1570161111666131219095114] [PMID: 24350930]
[9]
Jirillo E, Candore G, Magrone T, Caruso C. A scientific approach to anti-ageing therapies: state of the art. Curr Pharm Des 2008; 14(26): 2637-42.
[http://dx.doi.org/10.2174/138161208786264070] [PMID: 18991682]
[10]
Longo VD, Antebi A, Bartke A, et al. Interventions to slow aging in humans: are we ready? Aging Cell 2015; 14(4): 497-510.
[http://dx.doi.org/10.1111/acel.12338] [PMID: 25902704]
[11]
Accardi G, Ligotti ME, Candore G. Phenotypic aspects of longevity. In: Caruso C, Ed., Centenarians. An Example of Positive Biology. Switzerland: Springer 2019; 23-34.
[http://dx.doi.org/10.1007/978-3-030-20762-5_2]
[12]
Caruso C, Passarino G, Puca A, Scapagnini G. “Positive biology”: the centenarian lesson. Immun Ageing 2012; 9(1): 5.
[http://dx.doi.org/10.1186/1742-4933-9-5] [PMID: 22524297]
[13]
Accardi G, Aprile S, Candore G, et al. Genotypic and phenotypic aspects of longevity: results from a Sicilian survey and implication for the prevention and the treatment of age-related diseases. Curr Pharm Des 2019; 25(3): 228-35.
[http://dx.doi.org/10.2174/1381612825666190313115233] [PMID: 30864497]
[14]
Sebastiani P, Solovieff N, Dewan AT, et al. Genetic signatures of exceptional longevity in humans. PLoS One 2012; 7(1)e29848
[http://dx.doi.org/10.1371/journal.pone.0029848] [PMID: 22279548]
[15]
Villa F, Ferrario A, Puca AA. Genetic signatures of centenarians. In: Caruso C, Ed., Centenarians. An Example of Positive Biology. Switzerland: Springer 2019; 87-97.
[http://dx.doi.org/10.1007/978-3-030-20762-5_6]
[16]
Brooks-Wilson AR. Genetics of healthy aging and longevity. Hum Genet 2013; 132(12): 1323-38.
[http://dx.doi.org/10.1007/s00439-013-1342-z] [PMID: 23925498]
[17]
Ferrario A, Puca AA. Genetic Studies in long living individuals: potential and limitations. In: Accardi G & Caruso C, Eds., Proc. Symposium Updates in Pathobiology. Causality and chance in Ageing, Age-related diseases and Longevity, Palermo, Unipapress 2017 39-52.
[18]
Corbo RM, Scacchi R, Apolipoprotein E, Apolipoprotein E, Apolipoprotein E. APOE) allele distribution in the world. Is APOE*4 a ‘thrifty’ allele? Ann Hum Genet 1999; 63(Pt 4): 301-10.
[http://dx.doi.org/10.1046/j.1469-1809.1999.6340301.x] [PMID: 10738542]
[19]
Aiello A, Accardi G, Candore G, et al. Nutrigerontology: a key for achieving successful ageing and longevity. Immun Ageing 2016; 13: 17.
[http://dx.doi.org/10.1186/s12979-016-0071-2] [PMID: 27213002]
[20]
Di Bona D, Accardi G, Virruso C, Candore G, Caruso C. Association between genetic variations in the insulin/insulin-like growth factor (Igf-1) signaling pathway and longevity: a systematic review and meta-analysis. Curr Vasc Pharmacol 2014; 12(5): 674-81.
[http://dx.doi.org/10.2174/1570161111666131218152807] [PMID: 24350933]
[21]
Sebastiani P, Gurinovich A, Nygaard M, et al. APOE Alleles and extreme human longevity. J Gerontol A Biol Sci Med Sci 2019; 74(1): 44-51.
[http://dx.doi.org/10.1093/gerona/gly174] [PMID: 30060062]
[22]
Anselmi CV, Malovini A, Roncarati R, et al. Association of the FOXO3A locus with extreme longevity in a southern Italian centenarian study. Rejuvenation Res 2009; 12(2): 95-104.
[http://dx.doi.org/10.1089/rej.2008.0827] [PMID: 19415983]
[23]
Kops GJ, Dansen TB, Polderman PE, et al. Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress. Nature 2002; 419(6904): 316-21.
[http://dx.doi.org/10.1038/nature01036] [PMID: 12239572]
[24]
Revelas M, Thalamuthu A, Oldmeadow C, et al. Review and meta-analysis of genetic polymorphisms associated with exceptional human longevity. Mech Ageing Dev 2018; 175: 24-34.
[http://dx.doi.org/10.1016/j.mad.2018.06.002] [PMID: 29890178]
[25]
Malovini A, Accardi G, Aiello A, et al. Taste receptors, innate immunity and longevity: the case of TAS2R16 gene. Immun Ageing 2019; 16: 5.
[http://dx.doi.org/10.1186/s12979-019-0146-y] [PMID: 30833980]
[26]
Campa D, De Rango F, Carrai M, et al. Bitter taste receptor polymorphisms and human aging. PLoS One 2012; 7(11)e45232
[http://dx.doi.org/10.1371/journal.pone.0045232] [PMID: 23133589]
[27]
Lee RJ, Cohen NA. Taste receptors in innate immunity. Cell Mol Life Sci 2015; 72(2): 217-36.
[http://dx.doi.org/10.1007/s00018-014-1736-7] [PMID: 25323130]
[28]
Caruso C, Pandey JP, Puca AA. Genetics of exceptional longevity: possible role of GM allotypes. Immun Ageing 2018; 15: 25.
[http://dx.doi.org/10.1186/s12979-018-0133-8] [PMID: 30450118]
[29]
Villa F, Carrizzo A, Spinelli CC, et al. Genetic analysis reveals a longevity-associated protein modulating endothelial function and angiogenesis. Circ Res 2015; 117(4): 333-45.
[http://dx.doi.org/10.1161/CIRCRESAHA.117.305875] [PMID: 26034043]
[30]
Villa F, Carrizzo A, Ferrario A, et al. A model of evolutionary selection: the cardiovascular protective function of the longevity associated variant of BPIFB4. Int J Mol Sci 2018; 19(10): 19.
[http://dx.doi.org/10.3390/ijms19103229] [PMID: 30347645]
[31]
Ciaglia E, Montella F, Maciag A, et al. Longevity-Associated Variant of BPIFB4 Mitigates Monocyte-Mediated Acquired Immune Response. J Gerontol A Biol Sci Med Sci 2019; 74(Suppl. 1): S38-44.
[http://dx.doi.org/10.1093/gerona/glz036] [PMID: 31074771]
[32]
Malavolta M, Dato S, Villa F, et al. LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice. Aging (Albany NY) 2019; 11(16): 6555-68.
[http://dx.doi.org/10.18632/aging.102209] [PMID: 31461407]
[33]
Puca AA, Carrizzo A, Spinelli C, et al. Single systemic transfer of a human gene associated with exceptional longevity halts the progression of atherosclerosis and inflammation in ApoE knockout mice through a CXCR4-mediated mechanism. Eur Heart J 2019.pii: ehz459
[http://dx.doi.org/10.1093/eurheartj/ehz459] [PMID: 31289820]
[34]
Puca AA, Ferrario A, Maciag A, et al. Association of immunoglobulin GM allotypes with longevity in long-living individuals from Southern Italy. Immun Ageing 2018; 15: 26.
[http://dx.doi.org/10.1186/s12979-018-0134-7] [PMID: 30450119]
[35]
Bellizzi D, Guarasci F, Iannone F, et al. Epigenetics and ageing. In: Caruso C, Ed., Centenarians. An Example of Positive Biology. Switzerland: Springer 2019; 99-133.
[http://dx.doi.org/10.1007/978-3-030-20762-5_7]
[36]
Villa F, Malovini A, Carrizzo A, et al. Serum BPIFB4 levels classify health status in long-living individuals. Immun Ageing 2015; 12: 27.
[http://dx.doi.org/10.1186/s12979-015-0054-8] [PMID: 26675039]
[37]
Heyn H, Li N, Ferreira HJ, et al. Distinct DNA methylomes of newborns and centenarians. Proc Natl Acad Sci USA 2012; 109(26): 10522-7.
[http://dx.doi.org/10.1073/pnas.1120658109] [PMID: 22689993]
[38]
Austad SN, Hoffman JM. Is antagonistic pleiotropy ubiquitous in aging biology? Evol Med Public Health 2018; 2018(1): 287-94.
[http://dx.doi.org/10.1093/emph/eoy033] [PMID: 30524730]
[39]
Maklakov AA, Carlsson H, Denbaum P, et al. Antagonistically pleiotropic allele increases lifespan and late-life reproduction at the cost of early-life reproduction and individual fitness. Proc Biol Sci 2017; 284(1856) pii 20170376
[http://dx.doi.org/10.1098/rspb.2017.0376] [PMID: 28615498]
[40]
Vijg J, Suh Y. Genome instability and aging. Annu Rev Physiol 2013; 75: 645-68.
[http://dx.doi.org/10.1146/annurev-physiol-030212-183715] [PMID: 23398157]
[41]
Hasty P, Campisi J, Hoeijmakers J, van Steeg H, Vijg J. Aging and genome maintenance: lessons from the mouse? Science 2003; 299(5611): 1355-9.
[http://dx.doi.org/10.1126/science.1079161] [PMID: 12610296]
[42]
Oshima J, Kato H, Maezawa Y, Yokote K. RECQ helicase disease and related progeroid syndromes: RECQ2018 meeting. Mech Ageing Dev 2018; 173: 80-3.
[http://dx.doi.org/10.1016/j.mad.2018.05.002] [PMID: 29752965]
[43]
Tian X, Firsanov D, Zhang Z, et al. SIRT6 is responsible for more efficient DNA double-strand break repair in long-lived species. Cell 2019; 177(3): 622-638.e22.
[http://dx.doi.org/10.1016/j.cell.2019.03.043] [PMID: 31002797]
[44]
Choi JE, Mostoslavsky R. Sirtuins, metabolism, and DNA repair. Curr Opin Genet Dev 2014; 26: 24-32.
[http://dx.doi.org/10.1016/j.gde.2014.05.005] [PMID: 25005742]
[45]
Vazquez BN, Thackray JK, Serrano L. Sirtuins and DNA damage repair: SIRT7 comes to play. Nucleus 2017; 8(2): 107-15.
[http://dx.doi.org/10.1080/19491034.2016.1264552] [PMID: 28406750]
[46]
Canning D. The causes and consequences of demographic transition. Popul Stud (Camb) 2011; 65(3): 353-61.
[http://dx.doi.org/10.1080/00324728.2011.611372] [PMID: 21973179]
[47]
Campisi J, Kapahi P, Lithgow GJ, Melov S, Newman JC, Verdin E. From discoveries in ageing research to therapeutics for healthy ageing. Nature 2019; 571(7764): 183-92.
[http://dx.doi.org/10.1038/s41586-019-1365-2] [PMID: 31292558]
[48]
Aiello A, Farzaneh F, Candore G, et al. Immunosenescence and its hallmarks: how to oppose aging strategically? A review of potential options for therapeutic intervention. Front Immunol 2019; 10: 2247.
[http://dx.doi.org/10.3389/fimmu.2019.02247] [PMID: 31608061]
[49]
Ambrose KR, Golightly YM. Physical exercise as non-pharmacological treatment of chronic pain: Why and when. Best Pract Res Clin Rheumatol 2015; 29(1): 120-30.
[http://dx.doi.org/10.1016/j.berh.2015.04.022] [PMID: 26267006]
[50]
Trichopoulou A, Benetou V. Impact of Mediterranean Diet on Longevity. In: Caruso C, Ed., Centenarians. An Example of Positive Biology. Switzerland: Springer 2019; 161-168.
[http://dx.doi.org/10.1007/978-3-030-20762-5_10]
[51]
Leonardi GC, Accardi G, Monastero R, Nicoletti F, Libra M. Ageing: from inflammation to cancer. Immun Ageing 2018; 15: 1.
[http://dx.doi.org/10.1186/s12979-017-0112-5] [PMID: 29387133]
[52]
Krumholz HM, Normand SL, Wang Y. Trends in hospitalizations and outcomes for acute cardiovascular disease and stroke, 1999-2011. Circulation 2014; 130(12): 966-75.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.113.007787] [PMID: 25135276]
[53]
Govindaraju D, Atzmon G, Barzilai N. Genetics, lifestyle and longevity: lessons from centenarians. Appl Transl Genomics 2015; 4: 23-32.
[http://dx.doi.org/10.1016/j.atg.2015.01.001] [PMID: 26937346]
[54]
Aiello A, Accardi G, Candore G, et al. Nutrient sensing pathways as therapeutic targets for healthy ageing. Expert Opin Ther Targets 2017; 21(4): 371-80.
[http://dx.doi.org/10.1080/14728222.2017.1294684] [PMID: 28281903]
[55]
Shimazu T, Hirschey MD, Newman J, et al. Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 2013; 339(6116): 211-4.
[http://dx.doi.org/10.1126/science.1227166] [PMID: 23223453]
[56]
Barzilai N, Huffman DM, Muzumdar RH, Bartke A. The critical role of metabolic pathways in aging. Diabetes 2012; 61(6): 1315-22.
[http://dx.doi.org/10.2337/db11-1300] [PMID: 22618766]
[57]
de Kreutzenberg SV, Ceolotto G, Cattelan A, et al. Metformin improves putative longevity effectors in peripheral mononuclear cells from subjects with prediabetes. A randomized controlled trial. Nutr Metab Cardiovasc Dis 2015; 25(7): 686-93.
[http://dx.doi.org/10.1016/j.numecd.2015.03.007] [PMID: 25921843]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 25
ISSUE: 39
Year: 2019
Page: [4133 - 4138]
Pages: 6
DOI: 10.2174/1381612825666191112094544
Price: $65

Article Metrics

PDF: 23
HTML: 5