Genetics of aging and its impact on human longevity: theories and evidences that helps to prevent age-associated diseases

Ivana Beatrice Mânica da Cruz


Biogerontological studies about the factors that affect the human longevity and suscessful aging are highly relevant. Therefore, here this paper I review and coment some questions about currently aging theories, the existence (or not) of “longevity genes” and main genetics mechanisms potentially involved in aging and lifespan. From this review I also will consider the impact environment on genetic and epigenetic factors on human aging, health and longevity.


Genetics. Longevity. Aging.

Full Text:



World Health Organization. Health and Aging: a discussion paper. 2001; Acess in: WHO_NMH_HPS_01.1.pdf

Instituto Brasileiro de Geografia e Estatística (IBGE). Acesso em set. 2014.

Portrait F, Lindeboom M, Deeg D. Life expectancies in specific health states: results from a joint model of health status and mortality of older persons. Demography. 2001;38(4):525-36.

Baldoni AO, Pereira, LRL. O impacto do envelhecimento populacional brasileiro para o sistema de saúde sob a óptica da farmacoepidemiologia: uma revisão narrativa.

López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013; 153(6):1194-217.

Kirkwood TB. Understanding the odd science of aging. Cell 2005;120:437-47.

Trindade LS, Aigaki T, Peixoto AA, Balduino A, Mânica da Cruz IB, Heddle JG. A novel classification system for evolutionary aging theories. Front Genet. 2013; 6;4:25.

Trindade LS, Balduino A, Aigaki T, Heddle JG. Senemorphism: a novel perspective on aging patterns and its implication for diet-related biology. Biogerontology. 2012;13(4):457-66.

Bengtson VL, Schaie KW. (Eds.). Handbook of theories of aging. New York: Springer Publishing. 2009.

Hamilton WD. The moulding of senescence by natural selection. J Theor Biol. 1966; 12:12-45.

Levitis DA. Before senescence: the evolutionary demography of ontogenesis. Proc Biol Sci. 2011;278(1707):801-9.

Weismann A. Essays Upon Heredity and Kindred Biological Problems. Oxford: Clarendon Press; 1889.

Fisher RA. The Genetical Theory of Natural Selection. Oxford: Clarendon Press; 1930.

Medawar PB. An Unsolved Problem of Biology. London: H. K. Lewis; 1952.

Williams GC. Pleiotropy, natural selection and the evolution of senescence. Evolution 1957;11:398-411.

Charlesworth, B. Patterns of age-specific means and genetic variances of mortality rates predicted by the mutationaccumulation theory of aging. J Theor Biol. 2001;210: 47-65.

Kirkwood TBL. Evolution of ageing. Nature 1977;270: 301-4.

Rose MR. Evolutionary Biology of Aging. New York: Oxford University Press; 1991.

Moskalev AA, Pasyukova EG. From theories of aging to antiaging interventions. Front Genet. 2014;5:276.

Walker RF. Developmental theory of aging revisited: focus on causal and mechanistic links between development and senescence. Rejuvenation Res. 2011;14(4):429-36.

Brunet A, Berger SL. Epigenetics of aging and aging-related disease. J Gerontol A Biol Sci Med Sci. 2014;69 Suppl 1: S17-20.

Brooks-Wilson AR. Genetics of healthy aging and longevity. Hum Genet. 2013;132(12):1323-38.

Marchal J, Pifferi F, Aujard F. Resveratrol in mammals: effects on aging biomarkers, age-related diseases, and life span. Ann NY Acad Sci. 2013;1290:67-73.

Poulsen MM, Jørgensen JO, Jessen N, Richelsen B, Pedersen SB. Resveratrol in metabolic health: an overview of the current evidence and perspectives. Ann NY Acad Sci. 2013;1290:74-82.

The International SNP Map Working Group. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms Nature 2001;409: 928-933.

Garatachea N, Marín PJ, Lucia A. The ACE DD genotype and D-allele are associated with exceptional longevity: a meta-analysis. Ageing Res Rev. 2013;12(4):1079-87.

Da Cruz IB, Oliveira G, Taufer M, Leal NF, Schwanke CH, Glock L, Moriguchi Y, Moriguchi EH. Angiotensin I-converting enzyme gene polymorphism in two ethnic groups living in Brazil’s southern region: association with age. J Gerontol A Biol Sci Med Sci. 2003;58(9):M851-6.

Barker DJ, Hales CN, Fall CH, Osmond C, Phipps K, Clark PM. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia. 1993;36(1):62-7.

McCauley BS, Dang W. Histone methylation and aging: Lessons learned from model systems. Biochim Biophys Acta. 2014; S1874 9399(14)00114-X.

Simmons D. Epigenetic Influences and Disease. Nature Education 2008;1(1):6.

Whayne TF. Epigenetics in the development, modification, and prevention of cardiovascular disease. Mol Biol Rep. 2014 (in press).

Capri M, Santoro A, Garagnani P, Bacalini MG, Pirazzini C, Olivieri F, Procopio A, Salvioli S, Franceschi C. Genes Of Human Longevity: An Endless Quest? Curr Vasc Pharmacol. 2014 (in press).

Ghosh S, Zhou Z. Genetics of aging, progeria and lamin disorders.Curr Opin Genet Dev. 2014; 5:26C:41-46

Schwanke CH, da Cruz IB, Leal NF, Scheibe R, Moriguchi Y, Moriguchi EH. Analysis of the association betwee apolipoprotein E polymorphism and cardiovascular risk factors in an elderly population with longevity. Arq Bras Cardiol. 2002;78(6):561-79.

Terra N, Moriguchi Y, Bittencourt L, Trois RS, Piccoli JE, Cruz IB. Apolipoprotein E polymorphism in elderly Japanese-Brazilian immigrants does not explain the reduced cardiovascular risk factor incidence. Genet Mol Res. 201; 10(3):1975-85.

Prado-Lima PA, Chatkin JM, Taufer M, Oliveira G, Silveira E, Neto CA, Haggstram F, Bodanese LC, da Cruz IB. Polymorphism of 5HT2A serotonin receptor gene is implicated in smoking addiction. Am J Med Genet B Neuropsychiatr Genet. 2004;128B(1):90-3.

Prado-Lima PS, Cruz IB, Schwanke CH, Netto CA, Licinio J. Human food preferences are associated with a 5-HT(2A) serotonergic receptor polymorphism. Mol Psychiatry. 2006;11(10):889-91.

Schwanke CH, Bittencourt L, Noronha JA, Augustin SA, Jung IE, Cruz IB. Is there an association between T102C polymorphism of the serotonin receptor 2A gene and urinary incontinence? Braz J Med Biol Res. 2007;40(10):1315-22.

Noronha JA, Schwanke CH, Machado DC, Braga R, Lubianca JM, Sesti FL, de Toledo AF, da Cruz IB. Association between T102C polymorphism of serotonin 2A receptor gene and urinary incontinence in older women. J Investig Med. 2010;58(1):32-7.

Jobim PF, Prado-Lima PA, Schwanke CH, Giugliani R, Cruz IB. The polymorphism of the serotonin-2A receptor T102C is associated with age. Braz J Med Biol Res. 2008;41(11): 1018-23.

Mânica-Cattani MF, Bittencourt L, Rocha MI, Algarve TD, Bodanese LC, Rech R, Machado MM, Santos GF, Gottlieb MG, Schwanke CH, Piccoli JE, Duarte MF, Cruz IB. Association between interleukin-1 betapolymorphism (+3953) and obesity. Mol Cell Endocrinol. 2010;15;314(1):84-9.

Dröse S, Brandt U, Wittig, I. Mitochondrial respiratory chain complexes as sources and targets of thiol-based redoxregulation. Biochim Biophys. Acta 2014;1844:1344-54.

Holley AK, Dhar SK, Xu Y, St Clair DK. Manganese superoxide dismutase: beyond life and death. Amino A.

Kamiński MM, Röth D, Krammer PH, Gülow K. Mitochondria as oxidative signaling organelles in T-cell activation: physiological role and pathological implications. Arch Immunol Ther Exp. (Warsz) 2013;61:367 84.

Shimoda-Matsubayashi S, Matsumine H, Kobayashi T, Nakagawa-Hattori Y, Shimizu Y, Shimizu et al. Structural dimorphism in the mitochondrial targeting sequence in the human manganese superoxide dismutase gene. A predictive evidence for conformational change to influence

mitochondrial transport and a study of allelic association in Parkinson’s disease. Biochem. Biophys. Res Commun. 2006;226:561-5.

Sutton A, Imbert A, Igoudjil A, Descatoire V, Cazanave S, Pessayre D et al. The manganese superoxide dismutase Ala16Val dimorphism modulates both mitochondrial import and mRNA stability. Pharmacogenet. Genomics, 2005;15: 311-9.

Bica CG, de Moura da Silva LL, Toscani NV, da Cruz IB, Sá G, Graudenz MS, Zettler CG. MnSOD gene polymorphism association with steroid dependent cancer. Pathol Oncol Res. 2009;15(1):19-2.

Bica CG, da Silva LL, Toscani NV, Zettler CG, Gottlieb MG, Alexandre CO, Graudenz MS, Mânica da Cruz IB. Polymorphism (ALA16VAL) correlates with regional lymph node status in breast cancer. Cancer Genet Cytogenet. 2010;196(2):153-8.

Taufer M, Peres A, de Andrade VM, de Oliveira G, Sá G, do Canto ME, dos Santos AR, Bauer ME, da Cruz IB. Is the Val16Ala manganese superoxide dismutase polymorphism associated with the aging process? J Gerontol A Biol Sci Med Sci. 2005;60(4):432-8.

Duarte MM, Moresco RN, Duarte T, Santi A, Bagatini MD, Da Cruz IB, Schetinger MR, Loro VL. Oxidative stress in hypercholesterolemia and its association with Ala16Val superoxide dismutase gene polymorphism. Clin Biochem. 2010;43(13-14):1118-23.

Montano MA, Barrio Lera JP, Gottlieb MG, Schwanke CH, da Rocha MI, Manica-Cattani MF, dos Santos GF, da Cruz IB. Association between manganese superoxide dismutase (MnSOD) gene polymorphism and elderly obesity. Mol Cell Biochem. 2009;328(1-2):33-40.

Bresciani G, Cruz I., de Paz JA, Cuevas MJ, González-Gallego J. The MnSOD Ala16Val SNP: relevance to human diseases and interaction with environmental factors. Free Radic Res. 2013;47:781-92.

Ambrosone CB, Freudenheim JL, Thompson PA, Bowman E, Vena JE, Marshall et al. Manganese superoxide dismutase (MnSOD) genetic polymorphisms, dietary antioxidants and risk of breast cancer. Cancer Res. 1999;59:602-6.

Bresciani G, González-Gallego J, da Cruz IB, de Paz JA, Cuevas MJ. The Ala16Val MnSOD gene polymorphism modulates oxidative response to exercise. Clin Biochem. 2013;46:335-40.

Santos Montagner GF1, Sagrillo M, Machado MM, Almeida RC, Mostardeiro CP, Duarte MM, da Cruz IB. Toxicol In Vitro. Toxicological effects of ultraviolet radiation on lymphocyte cells with different manganese superoxide dismutase Ala16Val polymorphism genotypes. 2010;24(5):1410-6.

Costa F, Dornelles E, Mânica-Cattani MF, Algarve TD, Souza Filho OC, Sagrillo MR, Garcia LF, Cruz IB. Influence of Val16Ala SOD2 polymorphism on the in-vitro effect of clomiphene citrate in oxidative metabolism. Reprod Biomed Online. 2012;24(4):474-81.

Algarve TD, Barbisan F, Ribeiro EE, Duarte MM, Mânica- Cattani MF, Mostardeiro CP, Lenz AF, da Cruz IB. In vitro effects of Ala16Val manganese superoxide dismutase gene polymorphism on human white blood cells exposed to methylmercury. Genet Mol Res. 2013;12(4):5134-44.

Montano MA, da Cruz IB, Duarte MM, Krewer Cda C, da Rocha MI, Mânica-Cattani MF, Soares FA, Rosa G, Maris AF, Battiston FG, Trott A, Lera JP. Inflammatory cytokines in vitro production are associated with Ala16Val superoxide dismutase gene polymorphism of peripheral blood mononuclear cells. Cytokine. 2012;60(1):30-3.

Barbisan F, Motta Jde R, Trott A, Azzolin V, Dornelles EB, Marcon M, Algarve TD, Duarte MM, Mostardeiro CP, Unfer TC, Schott KL, da Cruz IB. Methotrexate-Related Response on Human Peripheral Blood Mononuclear Cells May Be Modulated by the Ala16Val-SOD2 Gene Polymorphism.

PLoS One. 2014;9(10):e107299.

Kanherkar RR, Bhatia-Dey N, Csoka AB. Epigenetics across the human lifespan. Front Cell Dev Biol. 2014;2:49

Pembrey M, Saffery R2, Bygren LO3; Network in Epigenetic Epidemiology; Network in Epigenetic Epidemiology. Human transgenerational responses to early-life experience: potential impact on development, health and biomedical research. J Med Genet. 2014;51(9):563-72.

Maia Ribeiro EA, Ribeiro EE, Viegas K, Teixeira F, dos Santos Montagner GF, Mota KM, Barbisan F, da Cruz IB, de Paz JA. Functional, balance and health determinants of falls in a free living community Amazon riparian elderly. Arch Gerontol Geriatr. 2013;56(2):350-7.

da Costa Krewer C, Ribeiro EE, Ribeiro EA, Moresco RN, de Ugalde Marques da Rocha MI, Dos Santos Montagner GF, Machado MM, Viegas K, Brito E, da Cruz IB. 63. Habitual intake of guaraná and metabolic morbidities: an epidemiological study of an elderly amazonian population. Phytother Res. 2011;25(9):1367-74.

Portella Rde L, Barcelos RP, da Rosa EJ, Ribeiro EE, da Cruz IB, Suleiman L, Soares FA. Guaraná (Paullinia cupana Kunth) effects on LDL oxidation in elderly people: an in vitro and in vivo study. Lipids Health Dis. 2013; 12:12.

Bittencourt LS, Machado DC, Machado MM, Dos Santos GF, Algarve TD, Marinowic DR, Ribeiro EE, Soares FA, Barbisan F, Athayde ML, Cruz IB. The protective effects of guaraná extract (Paullinia cupana) on fibroblast NIH-3T3 cells exposed to sodium nitroprusside. Food Chem Toxicol.


Hertz E, Cadoná FC, Machado AK, Azzolin V, Holmirch S, Assmann C, Ledur P, Ribeiro EE, Souza Filho OC, Manica- Cattani MF, Cruz IBM. Effect of Paullinia cupana on MCF‑7 breast cancer cell response to chemotherapeutic drugs. Mol Clin Oncology. 2015;3:37-43.

Krewer CC, Suleiman L, Duarte MMF, Ribeiro EE, Mostardeiro CP, Montano MAE, da Rocha MIU, Algarve TD, Bresciani GB, Cruz IBM. Guaraná, a supplement rich in caffeine and catechin, modulates cytokines: evidence from human in vitro and in vivo protocols. European Food Research and Technology 2014;239(1):49-57.

Jobim ML, Santos RC, dos Santos Alves CF, Oliveira RM, Mostardeiro CP, Sagrillo MR, de Souza Filho OC, Garcia LF, Manica-Cattani MF, Ribeiro EE, da Cruz IB. Antimicrobial activity of Amazon Astrocaryum aculeatum extracts and its association to oxidative metabolism. Microbiol Res.


de Souza Filho OC, Sagrillo MR, Garcia LF, Machado AK, Cadoná F, Ribeiro EE, Duarte MM, Morel AF, da Cruz IB. The in vitro genotoxic effect of Tucuma (Astrocaryum aculeatum), an Amazonian fruit rich in carotenoids. J Med Food. 2013;16(11):1013-21.

Sagrillo MC, Garcia LFM, Souza Filho OC, Duarte MMF, Ribeiro EE, Cadoná FC, Cruz IBM. Tucumã fruit extracts (Astrocaryum aculeatum Meyer) decrease cytotoxic effects of hydrogen peroxide on human lymphocytes. Food Chem, 2015 (in press).


ISSN-L: 2357-9641

Except where otherwise specified, material published in this journal is licensed under a Creative Commons Attribution 4.0 International license, which allows unrestricted use, distribution and reproduction in any medium, provided the original publication is correctly cited.