Skip to main content
SpringerLink
Log in

Why and How Do We Age? A Single Answer to Two Questions

  • Published:
Advances in Gerontology Aims and scope Submit manuscript

Abstract

The chemical properties of the compounds involved in metabolic processes, even the core ones, such as glycolysis and the Krebs cycle, are not confined to the properties utilized in enzymatic reactions; they include the ability to spontaneously form covalent bonds with other compounds, including macromolecule components. The effects of the gene that codes for an enzyme catalyzing the formation of a metabolite with such properties may be regarded as antagonistically pleiotropic. The effects implemented via the product of the reaction catalyzed by the enzyme coded for by the gene are required to maintain viability. As for the effects mediated by the spontaneous formation of covalent bonds between this product and slowly renewable macromolecules, they are increasingly deleterious with time, which is provided by the positive effects. Thus, the antagonistically pleiotropic effects are not late-acting, as it is commonly believed, but are cumulative. Since these effects are inseparable from the metabolism, they may be labeled “parametabolic.” The driving force produced by these effects is sufficient for aging to take place in any system that exists due to metabolic processes therein, whereas its genetic information is stored and some other functions, e.g. bearing, are performed by macromolecular components, which feature a much slower turnover than that of the metabolites. Thus, we age because of the chemical properties of our constituents, and we do so as determined by these properties implemented under the conditions in our bodies. Aging is neither a direct product of evolution via natural selection (such as a program determining lifespan) nor a byproduct (delayed payment for current advantages). Aging results from the limitations imposed by the immanent physicochemical properties of metabolites on the capabilities and outcomes of the evolution by natural selection; this is what distinguishes aging from the tear and wear of inanimate objects.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.
Fig. 2.

Similar content being viewed by others

REFERENCES

  1. Al-Abed, Y., Schleicher, E., Voelter, W., et al., Identification of N2-(1-carboxymethyl)guanine (CMG) as a guanine advanced glycation end product, Bioorg. Med. Chem. Lett., 1998, vol. 8, pp. 2109–2110.

    Article  CAS  PubMed  Google Scholar 

  2. Aldini, G., Vistoli, G., Stefek, M., et al., Molecular strategies to prevent, inhibit, and degrade advanced glycoxidation and advanced lipoxidation end products, Free Radical Res., 2013, vol. 47, suppl., pp. 93–137.

    Article  CAS  Google Scholar 

  3. Allaman, I., Belanger, M., and Magistretti, P.J., Methylglyoxal, the dark side of glycolysis, Front. Neurosci., 2015, vol. 9, no. 23. https://doi.org/10.3389/fnins.2015.00023

  4. Asanuma, M., Miyazaki, I., and Ogawa, N., Dopamine- or L-DOPA-induced neurotoxicity: the role of dopamine quinone formation and tyrosinase in a model of Parkinson’s disease, Neurotoxic. Res., 2003, vol. 5, pp. 165–176.

    Article  Google Scholar 

  5. Barja, G., The mitochondrial free radical theory of aging, Prog. Mol. Biol. Transl. Sci., 2014, vol. 127, pp. 1–27.

    Article  CAS  PubMed  Google Scholar 

  6. Belarbi, K., Cuvelier, E., Destee, A., et al., NADPH oxidases in Parkinson’s disease: a systematic review, Mol. Neurodegener., 2017, vol. 12, no. 1, p. 84. https://doi.org/10.1186/s13024-017-0225-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Bhat, W.F., Bhat, S.A., Khaki, P. S.S., and Bano, B., Employing in vitro analysis to test the potency of methylglyoxal in inducing the formation of amyloid-like aggregates of caprine brain cystatin, Amino Acids, 2015, vol. 47, pp. 135–146.

    Article  CAS  PubMed  Google Scholar 

  8. Bhatia-Dey, N., Kanherkar, R.R., Stair, S.E., et al., B. Cellular Senescence as the causal nexus of aging, Front. Genet., 2016, vol. 7, p. 13. https://doi.org/10.3389/fgene.2016.00013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bilinski, T., Bylak, A., and Zadrag-Tecza, R., Principles of alter native gerontology, Aging (N.Y.), 2016, vol. 8, no. 4, pp. 589–602.

    Article  Google Scholar 

  10. Bjorksten, J. and Tenhu, H., The cross-linking theory of aging: added evidence, Exp. Gerontol., 1990, vol. 25, pp. 91–95.

    Article  CAS  PubMed  Google Scholar 

  11. Carter, A.J. and Nguyen, A.Q., Antagonistic pleiotropy as a widespread mechanism for the maintenance of polymorphic disease alleles, BMC Med. Genet., 2011, vol. 12, p. 160. https://doi.org/10.1186/1471-2350-12-160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Caspi, R., Billington, R., Ferrer, L., et al., The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases, Nucleic Acids Res., 2016, vol. 44, pp. D471–D480.

    Article  CAS  PubMed  Google Scholar 

  13. Cavalieri, E.L., Rogan, E.G., and Chakravarti, D., Initiation of cancer and other diseases by catechol ortho-quinones: a unifying mechanism, Cell. Mol. Life Sci., 2002, vol. 59, pp. 665–681.

    Article  CAS  PubMed  Google Scholar 

  14. Chaleckis, R., Murakami, I., Takada, J., et al., Individual variability in human blood metabolites identifies age-related differences, Proc. Natl. Acad. Sci. U.S.A., 2016, vol. 113, pp. 4252–4259.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Coles, L.S. and Young, R.D., Supercentenarians and transthyretin amyloidosis: the next frontier of human life extension, Prev. Med., 2012, vol. 54, suppl., pp. S9–S11.

    Article  CAS  PubMed  Google Scholar 

  16. Currais, A., Goldberg, J., Farrokhi, C., et al., A comprehensive multiomics approach toward understanding the relationship between aging and dementia, Aging (N.Y.), 2015, vol. 7, pp. 937–955.

    Article  CAS  Google Scholar 

  17. Da Costa, J.P., Vitorino, R., Silva, G.M., et al., A synopsis on aging—theories, mechanisms and future prospects, Ageing Res. Rev., 2016, vol. 29, pp. 90–112.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Dammann, P., Sell, D.R., Begall, S., et al., Advanced glycation end-products as markers of aging and longevity in the long-lived Ansell’s mole-rat (Fukomys anselli), J. Gerontol., Ser. A, 2012, vol. 67, pp. 573–583.

    Google Scholar 

  19. Distler, M.G., Plant, L.D., Sokoloff, G., et al., Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal, J. Clin. Invest., 2012, vol. 122, pp. 2306–2315.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Dong, X., Milholland, B., and Vijg, J., Evidence for a limit to human lifespan, Nature, 2016, vol. 538, pp. 257–259.

    Article  CAS  PubMed  Google Scholar 

  21. Drenos, F. and Kirkwood, T.B., Modeling the disposable soma theory of ageing, Mech. Ageing Dev., 2005, vol. 126, pp. 99–103.

    Article  PubMed  Google Scholar 

  22. Droge, W., Oxidative stress and aging, Adv. Exp. Med. Biol., 2003, vol. 543, pp. 191–200.

    Article  CAS  PubMed  Google Scholar 

  23. Gavrilov, L.A. and Gavrilova, N.A., Theoretical perspectives on biodemography of aging and longevity, in Handbook of Theories of Aging, Vern, L. and Bengtson, R.A.S., Eds., New York: Springer-Verlag, 2016, pp. 643–667.

    Google Scholar 

  24. Gebauer, J., Gentsch, C., Mansfeld, J., et al., A genome-scale database and reconstruction of Caenorhabditis elegans metabolism, Cell. Syst., 2016, vol. 2, pp. 312–322.

    Article  CAS  PubMed  Google Scholar 

  25. Gensler, H.L. and Bernstein, H., DNA damage as the primary cause of aging, Q. Rev. Biol., 1981, vol. 56, pp. 279–303.

    Article  CAS  PubMed  Google Scholar 

  26. Gladyshev, V.N., The origin of aging: imperfectness-driven non-random damage defines the aging process and control of lifespan, Trends Genet., 2013, vol. 29, pp. 506–512.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Gladyshev, V.N., Aging: progressive decline in fitness due to the rising deleteriome adjusted by genetic, environmental, and stochastic processes, Aging Cell, 2016, vol. 15, pp. 594–602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Goldford, J.E. and Segrè, D., Modern views of ancient metabolic networks, Curr. Opin. Syst. Biol., 2018, vol. 8, pp. 117–124.

    Article  Google Scholar 

  29. Goldsmith, T.P., Emerging programmed aging mechanisms and their medical implications, Med. Hypotheses, 2016, vol. 86, pp. 92–96.

    Article  PubMed  Google Scholar 

  30. Goldstein, D.S., Kopin, I.J., and Sharabi, Y., Catecholamine autotoxicity. Implications for pharmacology and therapeutics of Parkinson disease and related disorders, Pharmacol. Ther., 2014, vol. 144, pp. 268–282.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Golubev, A., How could the Gompertz-Makeham law evolve, J. Theor. Biol., 2009, vol. 258, pp. 1–17.

    Article  CAS  PubMed  Google Scholar 

  32. Golubev, A., Hanson, A.D., and Gladyshev, V.N., Nonenzymatic molecular damage as a prototypic driver of aging, J. Biol. Chem., 2017, vol. 292, pp. 6029–6038.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Golubev, A., Hanson, A.D., and Gladyshev, V.N., A tale of two concepts: harmonizing the free radical and antagonistic pleiotropy theories of aging, Antioxid. Redox Signaling, 2017. https://doi.org/10.1089/ars.2017.7105

  34. Golubev, A.G., Catecholamines, steroids and aging of the nervous and endocrine systems, Usp. Sovrem. Biol., 1989, no. 6, pp. 64–75.

  35. Golubev, A.G., The other side of metabolism: a review, Biochemistry (Moscow), 1996, vol. 61, no. 11, pp. 1443–1460.

    Google Scholar 

  36. Golubev, A.G., Evolution of lifespan and ageing, Biosfera, 2011, vol. 3, pp. 338–368.

    Google Scholar 

  37. Golubev, A.G., The issue of the feasibility of a general theory of aging. III. Theory and practice of aging, Adv. Gerontol., 2012, vol. 2, no. 2, pp. 109–119.

    Article  Google Scholar 

  38. Golubev, A.G., Commentary: Is life extension today a Faustian bargain?, Front. Med., 2018, vol. 5, no. 73. https://doi.org/10.3389/fmed.2018.00073

  39. Gomes, R.A., Vicente Miranda, H., Sousa Silva, M., et al., Protein glycation and methylglyoxal metabolism in yeast: finding peptide needles in protein haystacks, FEMS Yeast Res., 2008, vol. 8, pp. 174–181.

    Article  CAS  PubMed  Google Scholar 

  40. Gonidakis, S. and Longo, V.D., Assessing chronological aging in bacteria, Methods Mol. Biol. (N.Y.), 2013, vol. 965, pp. 421–437.

    Article  CAS  Google Scholar 

  41. Gorisse, L., Pietrement, C., Vuiblet, V., et al., Protein carbamylation is a hallmark of aging, Proc. Natl. Acad. Sci. U.S.A., 2016, vol. 113, pp. 1191–1196.

    Article  CAS  PubMed  Google Scholar 

  42. Grüning, N.-M., Du, D., Keller, M.A., et al., Inhibition of triosephosphate isomerase by phosphoenolpyruvate in the feedback-regulation of glycolysis, Open Biol., 2014, vol. 4, no. 3. https://doi.org/10.1098/rsob.130232

  43. Hamilton, W.D., The molding of senescence by natural selection, J. Theor. Biol., 1966, vol. 12, pp. 12–45.

    Article  CAS  PubMed  Google Scholar 

  44. Hanson, A.D., Henry, P.S., Fiehn, O., and de Crécy-Lagard, V., Metabolite damage and metabolite damage control in plants, Ann. Rev. Plant. Biol., 2016, vol. 67, pp. 131–152.

    Article  CAS  Google Scholar 

  45. Hare, D.J. and Double, K.L., Iron and dopamine: a toxic couple, Brain, 2016, vol. 139, no. 4, pp. 1026–1035.

    Article  PubMed  Google Scholar 

  46. Harman, D., Aging: a theory based on free radical and radiation chemistry, J. Gerontol., 1956, vol. 11, pp. 298–300.

    Article  CAS  PubMed  Google Scholar 

  47. Harman, D., Free radical theory of aging: effect of free radical reaction inhibitors on the mortality rate of male LAF mice, J. Gerontol., 1968, vol. 23, pp. 476–482.

    Article  CAS  PubMed  Google Scholar 

  48. Harman, D., The free radical theory of aging, Antioxid. Redox Signaling, 2003, vol. 5, pp. 557–561.

    Article  CAS  Google Scholar 

  49. Hawkes, K., Smith, K.R., and Blevins, J.K., Human actuarial aging increases faster when back ground death rates are lower: a consequence of differential heterogeneity?, Evolution, 2012, vol. 66, pp. 103–114.

    Article  PubMed  Google Scholar 

  50. Hoffman, J.M., Tran, V., Wachtman, L.M., et al., A longitudinal analysis of the effects of age on the blood plasma metabolome in the common marmoset, Callithrix jacchus, Exp. Gerontol., 2016, vol. 76, pp. 17–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Hofmann, J.W., Zhao, X., De Cecco, M., et al., Reduced expression of MYC increases longevity and enhances healthspan, Cell, 2015, vol. 160, pp. 477–488.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Hong, S.Y., Ng, L.V., Ng, L.F., et al., The role of mitochondrial non-enzymatic protein acylation in ageing, PLoS One, 2016, vol. 11, no. 12, p. e0168752.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Jasienska, G., Ellison, P.V., Galbarczyk, A., et al., Apolipoprotein E (ApoE) polymorphism is related to differences in potential fertility in women: a case of antagonistic pleiotropy?, Proc. R. Soc. B, 2015, vol. 282, art. ID. 20142395. https://doi.org/10.1098/rspb.2014.2395

  54. Johnson, S.C., Dong, X., Vijg, J., and Suh, Y., Genetic evidence for common pathways in human age-related diseases, Aging Cell, 2015, vol. 14, pp. 809–817.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kalapos, M.P., The tandem of free radicals and methylglyoxal, Chem.-Biol. Interact., 2008, vol. 171, pp. 251–271.

    Article  CAS  PubMed  Google Scholar 

  56. Kaushik, S. and Cuervo, A.M., Proteostasis and aging, Nat. Med., 2015, vol. 21, pp. 1406–1415.

    Article  CAS  PubMed  Google Scholar 

  57. Keller, M.A., Kampjut, D., Harrison, S.A., and Ralser, M., Sulfate radicals enable a non-enzymatic Krebs cycle precursor, Nat. Ecol. Evol., 2017, vol. 1, art. ID 0083. https://doi.org/10.1038/s41559-017-0083

    Article  PubMed Central  Google Scholar 

  58. Keller, M.A., Turchyn, A.V., and Ralser, M., Non-enzymatic glycolysis and pentose phosphate pathway-like reactions in a plausible Achaean ocean, Mol. Syst. Biol., 2014, vol. 10, no. 4. https://doi.org/10.1002/msb.20145228

  59. Kennedy, S.R., Loeb, L.A., and Herr, A.J., Somatic mutations in aging, cancer and neurodegeneration, Mech. Ageing Dev., 2012, vol. 133, pp. 118–126.

    Article  CAS  PubMed  Google Scholar 

  60. Kirkwood, T.B., Evolution of ageing, Nature, 1977, vol. 270, pp. 301–304.

    Article  CAS  PubMed  Google Scholar 

  61. Kirkwood, T.B., Deciphering death: a commentary on Gompertz (1825) ‘On the nature of the function expressive of the law of human mortality, and on a new mode of determining the value of life contingencies,’ Philos. Trans. R. Soc., B, 2015, vol. 370, no. 1666. https://doi.org/10.1098/rstb.2014.0379

  62. Kita, K., Kawashima, Y., Makino, R., et al., Detection of two types of glycated tryptophan compounds in the plasma of chickens fed tryptophan excess diets, J. Poultry Sci., 2013, vol. 50, pp. 138–142.

    Article  CAS  Google Scholar 

  63. Kowald, A. and Kirkwood, T.B., Can aging be programmed? A critical literature review, Aging Cell, 2016, vol. 15, pp. 986–998.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Kuklinski, N.J., Berglund, E.C., Engelbreksson, J., and Ewing, A.G., Determination of salsolinol, norsalsolinol, and twenty-one biogenic amines using micellar electrokinetic capillary chromatography–electrochemical detection, Electrophoresis, 2010, vol. 31, pp. 1886–1893.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Labbadia, J. and Morimoto, R.I., The biology of proteostasis in aging and disease, Ann. Rev. Biochem., 2015, vol. 84, pp. 435–464.

    Article  CAS  PubMed  Google Scholar 

  66. Lade, S.J., Coelho, M., Tolić, I.M., and Gross, T., Fusion leads to effective segregation of damage during cell division: an analytical treatment, J. Theor. Biol., 2015, vol. 378, pp. 47–55.

    Article  PubMed  Google Scholar 

  67. Lagunas-Rangel, F.A. and Chavez-Valencia, V., Learning of nature: the curious case of the naked mole rat, Mech. Ageing Dev., 2017, vol. 164, pp. 76–81.

    Article  PubMed  Google Scholar 

  68. Lambeth, J.D., Nox enzymes, ROS, and chronic disease: an example of antagonistic pleiotropy, Free Radicals Biol. Med., 2007, vol. 43, pp. 332–347.

    Article  CAS  Google Scholar 

  69. Laron, Z., Kauli, R., Lapkina, L., and Werner, H., IGF-I deficiency, longevity and cancer protection of patients with Laron syndrome, Mutat. Res., 2016, vol. 772, pp. 123–133.

    Article  CAS  Google Scholar 

  70. Laye, M.J., Tran, V., Jones, D.P., et al., The effects of age and dietary restriction on the tissue-specific metabolome of Drosophila, Aging Cell, 2015, vol. 14, pp. 797–808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Le Bourg, E., Evolutionary theories of aging can explain why we age, Interdiscip. Top. Gerontol., 2014, vol. 39, pp. 8–23.

    Article  PubMed  Google Scholar 

  72. Lerma-Ortiz, C., Jeffryes, J. G., Cooper, A.J.L., et al., ‘Nothing of chemistry disappears in biology’: the Top 30 damage-prone endogenous metabolites, Biochem. Soc. Trans., 2016, vol. 44, pp. 961–971.

    Article  CAS  PubMed  Google Scholar 

  73. Li, C., Xu, X., Tao, Z., et al., Resveratrol derivatives: an updated patent review (2012–2015), Expert Opin. Ther. Pat., 2016, vol. 26, pp. 1189–1200.

    Article  CAS  PubMed  Google Scholar 

  74. Limpert, E. and Stahel, W.A., The log-normal distribution, Significance, 2017, vol. 14, pp. 8–9.

    Google Scholar 

  75. Linster, P.L., van Schaftingen, E., and Hanson, A.D., Metabolite damage and its repair or pre-emption, Nat. Chem. Biol., 2013, vol. 9, pp. 72–80.

    Article  CAS  PubMed  Google Scholar 

  76. Lippincott, J. and Apostol, I., Carbamylation of cysteine: a potential artifact in peptide mapping of hemoglobins in the presence of urea, Anal. Biochem., 1999, vol. 267, pp. 57–64.

    Article  CAS  PubMed  Google Scholar 

  77. Longo, V.D., Antebi, A., Bartke, A., et al., Interventions to slow aging in humans: Are we ready?, Aging Cell, 2015, vol. 14, pp. 497–510.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Lutz, T.A. and Meyer, U., Amylin at the interface between metabolic and neurodegenerative disorders, Front. Neurosci., 2015, vol. 9. https://doi.org/10.3389/fnins.2015.00216

  79. Madimenos, F.P., An evolutionary and life-history perspective on osteoporosis, Ann. Rev. Anthropol., 2015, vol. 44, pp. 189–206.

    Article  Google Scholar 

  80. Manini, P., Napolitano, A., and d’Ischia, M., Reactions of d-glucose with phenolic amino acids: further insights into the competition between Maillard and Pictet–Spengler condensation pathways, Carbohydr. Res., 2005, vol. 340, pp. 2719–2727.

    Article  CAS  PubMed  Google Scholar 

  81. Matafome, P., Rodrigues, V., Sena, C., and Seiça, R., Methylglyoxal in metabolic disorders: facts, myths, and promises, Med. Res. Rev., 2016, vol. 37, pp. 368–403.

    Article  PubMed  Google Scholar 

  82. Matura, S., Prvulovic, D., Hartmann, D., et al., Age-related effects of the apolipoprotein E gene on brain function, J. Alzheimer’s Dis., 2016, vol. 52, pp. 317–331.

    Article  CAS  Google Scholar 

  83. McCann, S.M., Mastronardi, C., De Laurentiis, A., and Rettori, V., The nitric oxide theory of aging revisited, Ann. N.Y. Acad. Sci., 2005, vol. 1057, pp. 64–84.

    Article  CAS  PubMed  Google Scholar 

  84. Monnier, V.M., Genuth, S., and Sell, D.R., The pecking order of skin Advanced Glycation Endproducts (AGEs) as long-term markers of glycemic damage and risk factors for micro- and subclinical macrovascular disease progression in Type 1 diabetes, Glycoconjugate J., 2016, vol. 33, pp. 569–579.

    Article  CAS  Google Scholar 

  85. Monnier, V.M., Mustata, G.V., Biemel, K.L., et al., Cross-linking of the extracellular matrix by the Maillard reaction in aging and diabetes: An update on “a Puzzle Nearing Resolution,” Ann. N.Y. Acad. Sci., 2005, vol. 1043, pp. 533–544.

    Article  CAS  PubMed  Google Scholar 

  86. Mostafa, A.A., Randell, E.W., Vasdev, S.C., et al., Plasma protein advanced glycation end products, carboxymethyl cysteine, and carboxyethyl cysteine, are elevated and related to nephropathy in patients with diabetes, Mol. Cell. Biochem., 2007, vol. 302, pp. 35–42.

    Article  CAS  PubMed  Google Scholar 

  87. Naudí, A., Jové, M., Ayala, V., et al., Non-enzymatic modification of aminophospholipids by carbonyl-amine reactions, Int. J. Mol. Sci., 2013, vol. 14, pp. 3285–3313.

  88. Newman, S.J. and Easteal, S., Global patterns of human ageing, bioRxiv, 2017. https://doi.org/10.1101/124792

  89. Olshansky, S.J. and Carnes, B.A., Ever since Gompertz, Demography, 1997, vol. 34, pp. 1–15.

    Article  CAS  PubMed  Google Scholar 

  90. Oppelt, S.A., Sennott, E.M., and Tolan, D.R., Aldolase-B knockout in mice phenocopies hereditary fructose intolerance in humans, Mol. Genet. Metab., 2015, vol. 114, pp. 445–450.

    Article  CAS  PubMed  Google Scholar 

  91. Orosz, F., Oláh, J., and Ovádi, J., Triosephosphate isomerase deficiency: new insights into an enigmatic disease, Biochim. Biophys. Acta, Mol. Basis Dis., 2009, vol. 1792, pp. 1168–1174.

    Article  CAS  Google Scholar 

  92. Pamplona, R., Membrane phospholipids, lipoxidative damage and molecular integrity: a causal role in aging and longevity, Biochim. Biophys. Acta, Bioenerg., 2008, vol. 1777, pp. 1249–1262.

    Article  CAS  Google Scholar 

  93. Plucinska, K., Crouch, B., Koss, D., et al., Knock-in of human BACE1 cleaves murine APP and reiterates Alzheimer-like phenotypes, J. Neurosci., 2014, vol. 34, pp. 10710–10728.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Rabbani, N., Xue, M., and Thornalley, P.J., Dicarbonyls and glyoxalase in disease mechanisms and clinical therapeutics, Glycoconjugate J., 2016, vol. 33, pp. 513–525.

    Article  CAS  Google Scholar 

  95. Rabbani, N., Xue, M., and Thornalley, P.J., Methylglyoxal-induced dicarbonyl stress in aging and disease: first steps towards glyoxalase 1-based treatments, Clin. Sci., 2016, vol. 130, pp. 1677–1696.

    Article  CAS  PubMed  Google Scholar 

  96. Robins, C. and Conneely, K.N., Testing evolutionary models of senescence: traditional approaches and future directions, Hum. Genet., 2014, vol. 133, pp. 1451–1465.

    Article  PubMed  Google Scholar 

  97. Rose, M.R., Life history evolution with antagonistic pleiotropy and overlapping generations, Theor. Popul. Biol., 1985, vol. 28, pp. 342–358.

    Article  Google Scholar 

  98. Rose, M.R. and Graves, J.L., Jr., What evolutionary biology can do for gerontology, J. Gerontol., 1989, vol. 44, pp. B27–B29.

    Article  CAS  PubMed  Google Scholar 

  99. Ruby, J.G., Smith, M., and Buffenstein, R., Naked mole-rat mortality rates defy Gompertzian laws by not increasing with age, eLife, 2018, vol. 7. https://doi.org/10.7554/eLife.31157

  100. Rusted, J.M., Evans, S.L., King, S.L., et al., APOE ε4 polymorphism in young adults is associated with improved attention and indexed by distinct neural signatures, NeuroImage, 2013, vol. 65, pp. 364–373.

    Article  CAS  PubMed  Google Scholar 

  101. Sadowska-Bartosz, I. and Bartosz, G., Effect of antioxidants supplementation on aging and longevity, Biomed. Res. Int., 2014, vol. 2014, p. 17. https://doi.org/10.1155/2014/404680

    Article  CAS  Google Scholar 

  102. Schaible, R., Scheuerlein, A., Dańko, M.J., et al., Constant mortality and fertility over age in Hydra, Proc. Natl. Acad. Sci. U.S.A., 2015, vol. 112, pp. 15701–15706.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Schenkelaars, Q., Tomczyk, S., Wenger, Y., et al., Hydra, a model system for deciphering the mechanisms of aging and resistance to aging, bioRxiv, 2017. https://doi.org/10.1101/155804

  104. Schosserer, M., Grillari, J., and Breitenbach, M., The dual role of cellular senescence in developing tumors and their response to cancer therapy, Front. Oncol., 2017, vol. 7, no. 278. https://doi.org/10.3389/fonc.2017.00278

  105. Schreiber, G. and Richardson, S.J., The evolution of gene expression, structure and function of transthyretin, Comp. Biochem. Physiol., Part B: Biochem. Mol. Biol., 1997, vol. 116, pp. 137–160.

    Article  CAS  Google Scholar 

  106. Seifermann, M. and Epe, B., Oxidatively generated base modifications in DNA: Not only carcinogenic risk factor but also regulatory mark?, Free Radicals Biol. Med., 2017, vol. 107, pp. 258–265.

    Article  CAS  Google Scholar 

  107. Shen, X.-M., Zhang, F., and Dryhurst, G., Oxidation of dopamine in the presence of cysteine: Characterization of new toxic products, Chem. Res. Toxicol., 1997, vol. 10, pp. 147–155.

    Article  CAS  PubMed  Google Scholar 

  108. Sipe, J.D., Benson, M.D., Buxbaum, J.N., et al., Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines, Amyloid, 2016, vol. 23, pp. 209–213.

    Article  CAS  PubMed  Google Scholar 

  109. Susilo, R. and Rommelspacher, H., Formation of a β-carboline (1,2,3,4-tetrahydro-l-methyl-β-carboline-1-carboxylic acid) following intracerebroventricular injection of tryptamine and pyruvic acid, Naunyn-Schmiedeberg’s Arch. Pharmacol., 1987, vol. 335, pp. 70–76.

    Article  CAS  Google Scholar 

  110. Taghavi, F., Habibi-Rezaei, M., Amani, M., et al., The status of glycation in protein aggregation, Int. J. Biol. Macromol., 2016, vol. 100, pp. 67–74.

    Article  CAS  PubMed  Google Scholar 

  111. Thiele, I., Swainston, N., Fleming, R.M.T., et al., A community-driven global reconstruction of human metabolism, Nat. Biotechnol., 2013, vol. 31, pp. 419–425.

    Article  CAS  PubMed  Google Scholar 

  112. Ungewitter, E. and Scrable, H., Antagonistic pleiotropy and p53, Mech. Ageing Dev., 2009, vol. 130, pp. 10–17.

    Article  CAS  PubMed  Google Scholar 

  113. Vaiserman, A. and Lushchak, O., Implementation of longevity-promoting supplements and medications in public health practice: achievements, challenges and future perspectives, J. Transl. Med., 2017, vol. 15, no. 1, p. 160. https://doi.org/10.1186/s12967-017-1259-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. van Exel, E., Koopman, J.J.E., Bodegom, D.V., et al., Effect of APOE ε4 allele on survival and fertility in an adverse environment, PLoS One, 2017, vol. 12, no. 7, p. e0179497.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Vaupel, J. W., Carey, J.R., Christensen, K., et al., Biodemographic trajectories of longevity, Science, 1998, vol. 280, pp. 855–860.

    Article  CAS  PubMed  Google Scholar 

  116. Vedel, S., Nunns, H., Košmrlj, A., et al., Asymmetric damage segregation constitutes an emergent population-level stress response, Cell Syst., 2016, vol. 3, pp. 187–198.

    Article  CAS  PubMed  Google Scholar 

  117. Vicente, M.H., El-Agnaf, O.M.A., and Outeiro, T.F., Glycation in Parkinson’s disease and Alzheimer’s disease, Mov. Disord., 2016, vol. 31, pp. 782–790.

    Article  CAS  Google Scholar 

  118. Williams, G.P., Pleiotropy, natural selection and the evolution of senescence, Evolution, 1957, vol. 11, pp. 398–411.

    Article  Google Scholar 

  119. Wishart, D.S., Mandal, R., Stanislaus, A., et al., Cancer metabolomics and the human metabolome database, Metabolites, 2016, vol. 6. https://doi.org/10.3390/metabo6010010

  120. Wlodek, L., Wrobel, M., and Czubak, J., Transamination and transsulphuration of L-cysteine in Ehrlich ascites tumor cells and mouse liver. The nonenzymatic reaction of L-cysteine with pyruvate, Int. J. Biochem., 1993, vol. 25, pp. 107–112.

    Article  CAS  PubMed  Google Scholar 

  121. Xie, B., Lin, F., Ullah, K., et al., A newly discovered neurotoxin ADTIQ associated with hyperglycemia and Parkinson’s disease, Biochem. Biophys. Res. Commun., 2015, vol. 459, pp. 361–366.

    Article  CAS  PubMed  Google Scholar 

  122. Yin, D. and Chen, K., The essential mechanisms of aging: Irreparable damage accumulation of biochemical side-reactions, Exp. Gerontol., 2005, vol. 40, pp. 455–465.

    Article  CAS  PubMed  Google Scholar 

  123. Zimniak, P., Relationship of electrophilic stress to aging, Free Radicals Biol. Med., 2011, vol. 51, pp. 1087–1105.

    Article  CAS  Google Scholar 

  124. Zimniak, P., What is the proximal cause of aging?, Front. Genet., 2012, vol. 3, no. 189. https://doi.org/10.3389/fgene.2012.00189

  125. Zucca, F.A., Segura-Aguilar, J., Ferrari, E., et al., Interactions of iron, dopamine, and neuromelanin pathways in brain aging and Parkinson’s disease, Prog. Neurobiol., 2015, vol. 155, pp. 96–119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Petrov National Medical Research Center of Oncology, 197758, St. Petersburg, Russia

    A. G. Golubev

Authors
  1. A. G. Golubev
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. G. Golubev.

Additional information

Translated by G. Chirikova

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Golubev, A.G. Why and How Do We Age? A Single Answer to Two Questions. Adv Gerontol 9, 1–14 (2019). https://doi.org/10.1134/S2079057019010065

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S2079057019010065

Keywords:

Search

Navigation