期刊论文详细信息
Immunity & Ageing
The application of genetics approaches to the study of exceptional longevity in humans: potential and limitations
Annibale A Puca2  Fiorella Araniti3  Alberto Malovini1  Francesco Villa3  Anna Ferrario3 
[1] University of Pavia, Via Ferrata 1, 27100, Pavia, Italy;Università degli Studi di Salerno, Via S. Allende, 84081, Baronissi, Italy;IRCCS Multimedica, Via Fantoli 16/15, 20138, Milan, Italy
关键词: Longevity;    Centenarians;    Aging;   
Others  :  817474
DOI  :  10.1186/1742-4933-9-7
 received in 2012-03-27, accepted in 2012-04-23,  发布年份 2012
PDF
【 摘 要 】

The average life-span of the population of industrialized countries has improved enormously over the last decades. Despite evidence pointing to the role of food intake in modulating life-span, exceptional longevity is still considered primarily an inheritable trait, as pointed out by the description of families with centenarian clusters and by the elevated relative probability of siblings of centenarians to become centenarians themselves. However, rather than being two separate concepts, the genetic origin of exceptional longevity and the more recently observed environment-driven increase in the average age of the population could possibly be explained by the same genetic variants and environmentally modulated mechanisms (caloric restriction, specific nutrients). In support of this hypothesis, polymorphisms selected for in the centenarian population as a consequence of demographic pressure have been found to modulate cellular signals controlled also by caloric restriction. Here, we give an overview of the recent findings in the field of the genetics of human exceptional longevity, of how some of the identified polymorphisms modulate signals also influenced by food intake and caloric restriction, of what in our view have been the limitations of the approaches used over the past years to study genetics (sib-pair-, candidate gene association-, and genome-wide association-studies), and briefly of the limitations and the potential of the new, high-throughput, next-generation sequencing techniques applied to exceptional longevity.

【 授权许可】

   
2012 Ferrario et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140711004245145.pdf 392KB PDF download
Figure 1. 61KB Image download
【 图 表 】

Figure 1.

【 参考文献 】
  • [1]Perls TT: The different paths to 100. Am J Clin Nutr 2006, 83:484S-487S.
  • [2]Oeppen J, Vaupel JW: Demography. Broken limits to life expectancy. Science 2002, 296:1029-1031.
  • [3]Trichopoulou A, Orfanos P, Norat T, Bueno-de-Mesquita B, Ocke MC, Peeters PH, van der Schouw YT, Boeing H, Hoffmann K, Boffetta P, et al.: Modified Mediterranean diet and survival: EPIC-elderly prospective cohort study. BMJ 2005, 330:991.
  • [4]Terry DF, Sebastiani P, Andersen SL, Perls TT: Disentangling the roles of disability and morbidity in survival to exceptional old age. Arch Intern Med 2008, 168:277-283.
  • [5]Perls T, Shea-Drinkwater M, Bowen-Flynn J, Ridge SB, Kang S, Joyce E, Daly M, Brewster SJ, Kunkel L, Puca AA: Exceptional familial clustering for extreme longevity in humans. J Am Geriatr Soc 2000, 48:1483-1485.
  • [6]Perls TT, Wilmoth J, Levenson R, Drinkwater M, Cohen M, Bogan H, Joyce E, Brewster S, Kunkel L, Puca A: Life-long sustained mortality advantage of siblings of centenarians. Proc Natl Acad Sci U S A 2002, 99:8442-8447.
  • [7]Schachter F, Faure-Delanef L, Guenot F, Rouger H, Froguel P, Lesueur-Ginot L, Cohen D: Genetic associations with human longevity at the APOE and ACE loci. Nat Genet 1994, 6:29-32.
  • [8]Terry DF, Wilcox MA, McCormick MA, Pennington JY, Schoenhofen EA, Andersen SL, Perls TT: Lower all-cause, cardiovascular, and cancer mortality in centenarians’ offspring. J Am Geriatr Soc 2004, 52:2074-2076.
  • [9]Terry DF, McCormick M, Andersen S, Pennington J, Schoenhofen E, Palaima E, Bausero M, Ogawa K, Perls TT, Asea A: Cardiovascular disease delay in centenarian offspring: role of heat shock proteins. Ann N Y Acad Sci 2004, 1019:502-505.
  • [10]Barzilai N, Atzmon G, Schechter C, Schaefer EJ, Cupples AL, Lipton R, Cheng S, Shuldiner AR: Unique lipoprotein phenotype and genotype associated with exceptional longevity. JAMA 2003, 290:2030-2040.
  • [11]Puca AA, Andrew P, Novelli V, Anselmi CV, Somalvico F, Cirillo NA, Chatgilialoglu C, Ferreri C: Fatty acid profile of erythrocyte membranes as possible biomarker of longevity. Rejuvenation Res 2008, 11:63-72.
  • [12]Paolisso G, Gambardella A, Ammendola S, D’Amore A, Balbi V, Varricchio M, D’Onofrio F: Glucose tolerance and insulin action in healty centenarians. Am J Physiol 1996, 270:E890-E894.
  • [13]Zulfiqar U, Jurivich DA, Gao W, Singer DH: Relation of high heart rate variability to healthy longevity. Am J Cardiol 2010, 105:1181-1185.
  • [14]Hardie DG: Adenosine monophosphate-activated protein kinase: a central regulator of metabolism with roles in diabetes, cancer, and viral infection. Cold Spring Harb Symp Quant Biol 2011. Epub ahead of print
  • [15]Zong H, Ren JM, Young LH, Pypaert M, Mu J, Birnbaum MJ, Shulman GI: AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc Natl Acad Sci U S A 2002, 99:15983-15987.
  • [16]Hardie DG: AMPK and autophagy get connected. EMBO J 2011, 30:634-635.
  • [17]Hardie DG: AMPK: a key regulator of energy balance in the single cell and the whole organism. Int J Obes (Lond) 2008, 32(Suppl 4):S7-S12.
  • [18]Flachsbart F, Croucher PJ, Nikolaus S, Hampe J, Cordes C, Schreiber S, Nebel A: Sirtuin 1 (SIRT1) sequence variation is not associated with exceptional human longevity. Exp Gerontol 2006, 41:98-102.
  • [19]Imaizumi K: Diet and atherosclerosis in apolipoprotein E-deficient mice. Biosci Biotechnol Biochem 2011, 75:1023-1035.
  • [20]Willcox BJ, Donlon TA, He Q, Chen R, Grove JS, Yano K, Masaki KH, Willcox DC, Rodriguez B, Curb JD: FOXO3A genotype is strongly associated with human longevity. Proc Natl Acad Sci U S A 2008, 105:13987-13992.
  • [21]Malovini A, Illario M, Iaccarino G, Villa F, Ferrario A, Roncarati R, Anselmi CV, Novelli V, Cipolletta E, Leggiero E, et al.: Association study on long-living individuals from Southern Italy identifies rs10491334 in the CAMKIV gene that regulates survival proteins. Rejuvenation Res 2011, 14:283-291.
  • [22]Anselmi CV, Malovini A, Roncarati R, Novelli V, Villa F, Condorelli G, Bellazzi R, Puca AA: Association of the FOXO3A locus with extreme longevity in a southern Italian centenarian study. Rejuvenation Res 2009, 12:95-104.
  • [23]Flachsbart F, Caliebe A, Kleindorp R, Blanche H, von Eller-Eberstein H, Nikolaus S, Schreiber S, Nebel A: Association of FOXO3A variation with human longevity confirmed in German centenarians. Proc Natl Acad Sci U S A 2009, 106:2700-2705.
  • [24]Soerensen M, Dato S, Christensen K, McGue M, Stevnsner T, Bohr VA, Christiansen L: Replication of an association of variation in the FOXO3A gene with human longevity using both case–control and longitudinal data. Aging Cell 2010, 9:1010-1017.
  • [25]Kenyon CJ: The genetics of ageing. Nature 2010, 464:504-512.
  • [26]Kops GJ, Dansen TB, Polderman PE, Saarloos I, Wirtz KW, Coffer PJ, Huang TT, Bos JL, Medema RH, Burgering BM: Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress. Nature 2002, 419:316-321.
  • [27]van der Horst A, Burgering BM: Stressing the role of FoxO proteins in lifespan and disease. Nat Rev Mol Cell Biol 2007, 8:440-450.
  • [28]Guevara-Aguirre J, Balasubramanian P, Guevara-Aguirre M, Wei M, Madia F, Cheng CW, Hwang D, Martin-Montalvo A, Saavedra J, Ingles S, et al.: Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Sci Transl Med 2011, 3:70ra13.
  • [29]Pawlikowska L, Hu D, Huntsman S, Sung A, Chu C, Chen J, Joyner AH, Schork NJ, Hsueh WC, Reiner AP, et al.: Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity. Aging Cell 2009, 8:460-472.
  • [30]Sebastiani P, Montano M, Puca A, Solovieff N, Kojima T, Wang MC, Melista E, Meltzer M, Fischer SE, Andersen S, et al.: RNA editing genes associated with extreme old age in humans and with lifespan in C. elegans. PLoS One 2009, 4:e8210.
  • [31]Atzmon G, Cho M, Cawthon RM, Budagov T, Katz M, Yang X, Siegel G, Bergman A, Huffman DM, Schechter CB, et al.: Evolution in health and medicine Sackler colloquium: Genetic variation in human telomerase is associated with telomere length in Ashkenazi centenarians. Proc Natl Acad Sci U S A 2010, 107(Suppl 1):1710-1717.
  • [32]Novelli V, Viviani Anselmi C, Roncarati R, Guffanti G, Malovini A, Piluso G, Puca AA: Lack of replication of genetic associations with human longevity. Biogerontology 2008, 9:85-92.
  • [33]Altshuler D, Daly MJ, Lander ES: Genetic mapping in human disease. Science 2008, 322:881-888.
  • [34]Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D: Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 2006, 38:904-909.
  • [35]Ioannidis JP, Thomas G, Daly MJ: Validating, augmenting and refining genome-wide association signals. Nat Rev Genet 2009, 10:318-329.
  • [36]Deelen J, Beekman M, Uh HW, Helmer Q, Kuningas M, Christiansen L, Kremer D, van der Breggen R, Suchiman HE, Lakenberg N, et al.: Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited. Aging Cell 2011, 10:686-698.
  • [37]Nebel A, Kleindorp R, Caliebe A, Nothnagel M, Blanche H, Junge O, Wittig M, Ellinghaus D, Flachsbart F, Wichmann HE, et al.: A genome-wide association study confirms APOE as the major gene influencing survival in long-lived individuals. Mech Ageing Dev 2011, 132:324-330.
  • [38]Levy D, Larson MG, Benjamin EJ, Newton-Cheh C, Wang TJ, Hwang SJ, Vasan RS, Mitchell GF: Framingham Heart Study 100 K Project: genome-wide associations for blood pressure and arterial stiffness. BMC Med Genet 2007, 8(Suppl 1):S3. BioMed Central Full Text
  • [39]Benigni A, Corna D, Zoja C, Sonzogni A, Latini R, Salio M, Conti S, Rottoli D, Longaretti L, Cassis P, et al.: Disruption of the Ang II type 1 receptor promotes longevity in mice. J Clin Invest 2009, 119:524-530.
  • [40]Landers JE, Melki J, Meininger V, Glass JD, van den Berg LH, van Es MA, Sapp PC, van Vught PW, McKenna-Yasek DM, Blauw HM, et al.: Reduced expression of the Kinesin-Associated Protein 3 (KIFAP3) gene increases survival in sporadic amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A 2009, 106:9004-9009.
  • [41]Bolger TA, Zhao X, Cohen TJ, Tsai CC, Yao TP: The neurodegenerative disease protein ataxin-1 antagonizes the neuronal survival function of myocyte enhancer factor-2. J Biol Chem 2007, 282:29186-29192.
  • [42]Blaeser F, Ho N, Prywes R, Chatila TA: Ca(2+)-dependent gene expression mediated by MEF2 transcription factors. J Biol Chem 2000, 275:197-209.
  • [43]Racioppi L, Means AR: Calcium/calmodulin-dependent kinase IV in immune and inflammatory responses: novel routes for an ancient traveller. Trends Immunol 2008, 29:600-607.
  • [44]Ohmae S, Takemoto-Kimura S, Okamura M, Adachi-Morishima A, Nonaka M, Fuse T, Kida S, Tanji M, Furuyashiki T, Arakawa Y, et al.: Molecular identification and characterization of a family of kinases with homology to Ca2+/calmodulin-dependent protein kinases I/IV. J Biol Chem 2006, 281:20427-20439.
  • [45]Newton-Cheh C, Guo CY, Wang TJ, O’Donnell CJ, Levy D, Larson MG: Genome-wide association study of electrocardiographic and heart rate variability traits: the Framingham Heart Study. BMC Med Genet 2007, 8(Suppl 1):S7. BioMed Central Full Text
  • [46]Thayer JF, Yamamoto SS, Brosschot JF: The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors. Int J Cardiol 2010, 141:122-131.
  • [47]Sebastiani P, Solovieff N, Dewan AT, Walsh KM, Puca A, Hartley SW, Melista E, Andersen S, Dworkis DA, Wilk JB, et al.: Genetic signatures of exceptional longevity in humans. PLoS One 2012, 7:e29848.
  • [48]Puca AA, Daly MJ, Brewster SJ, Matise TC, Barrett J, Shea-Drinkwater M, Kang S, Joyce E, Nicoli J, Benson E, et al.: A genome-wide scan for linkage to human exceptional longevity identifies a locus on chromosome 4. Proc Natl Acad Sci U S A 2001, 98:10505-10508.
  • [49]Reed T, Dick DM, Uniacke SK, Foroud T, Nichols WC: Genome-wide scan for a healthy aging phenotype provides support for a locus near D4S1564 promoting healthy aging. J Gerontol A Biol Sci Med Sci 2004, 59:227-232.
  • [50]Beekman M, Blauw GJ, Houwing-Duistermaat JJ, Brandt BW, Westendorp RG, Slagboom PE: Chromosome 4q25, microsomal transfer protein gene, and human longevity: novel data and a meta-analysis of association studies. J Gerontol A Biol Sci Med Sci 2006, 61:355-362.
  • [51]Boyden SE, Kunkel LM: High-density genomewide linkage analysis of exceptional human longevity identifies multiple novel loci. PLoS One 2010, 5:e12432.
  • [52]Geesaman BJ, Benson E, Brewster SJ, Kunkel LM, Blanche H, Thomas G, Perls TT, Daly MJ, Puca AA: Haplotype-based identification of a microsomal transfer protein marker associated with the human lifespan. Proc Natl Acad Sci U S A 2003, 100:14115-14120.
  • [53]Nebel A, Croucher PJ, Stiegeler R, Nikolaus S, Krawczak M, Schreiber S: No association between microsomal triglyceride transfer protein (MTP) haplotype and longevity in humans. Proc Natl Acad Sci U S A 2005, 102:7906-7909.
  • [54]Matsuzaka T, Shimano H, Yahagi N, Kato T, Atsumi A, Yamamoto T, Inoue N, Ishikawa M, Okada S, Ishigaki N, et al.: Crucial role of a long-chain fatty acid elongase, Elovl6, in obesity-induced insulin resistance. Nat Med 2007, 13:1193-1202.
  • [55]Morcillo S, Martin-Nunez GM, Rojo-Martinez G, Almaraz MC, Garcia-Escobar E, Mansego ML, de Marco G, Chaves FJ, Soriguer F: ELOVL6 genetic variation is related to insulin sensitivity: a new candidate gene in energy metabolism. PLoS One 2011, 6:e21198.
  • [56]Cao H, Gerhold K, Mayers JR, Wiest MM, Watkins SM, Hotamisligil GS: Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell 2008, 134:933-944.
  • [57]Shmookler Reis RJ, Xu L, Lee H, Chae M, Thaden JJ, Bharill P, Tazearslan C, Siegel E, Alla R, Zimniak P, Ayyadevara S: Modulation of lipid biosynthesis contributes to stress resistance and longevity of C. elegans mutants. Aging (Albany NY) , 3:125-147.
  • [58]Friedman N, Geiger D, Goldszmidt M: Bayesian Network Classifiers. Mach Learn 1997, 29:131-163.
  • [59]Breiman L, Friedman JH, Olshen RA, Stone CJ: Classification and regression trees. Wadsworth & Brooks/Cole Advanced Books & Software, Monterey; 1984.
  • [60]Crammer K, Singer Y: On the algorithmic implementation of multiclass kernel-based vector machines. J Mach Learn Res 2001, 2:265-292.
  文献评价指标  
  下载次数:3次 浏览次数:6次