Encyclopedia of Gerontology and Population Aging

Living Edition
| Editors: Danan Gu, Matthew E. Dupre

Genetic Theories of Aging

  • Cristina GiulianiEmail author
  • Paolo Garagnani
  • Claudio Franceschi
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-69892-2_731-1

Definition

The aging theories are a very high number, and also many scientists proposed different ways of dividing and categorizing them. As a major subset of these theories, the genetic theories of aging include three main concepts: (1) the genetics of aging can be interpreted in the light of the evolutionary theories; (2) the genetics of aging and longevity can be informative if ecological and anthropological views are considered; (3) the genetics components underpin all the theories of aging even if not specifically stated.

Overview

Aging and longevity (as well as each phenotype and complex trait) are the results of complex gene-environment interactions (GxE), and in modern humans, the dimension of the environment is very heterogeneous as it includes the cultural dimension and the ecological one (Giuliani et al. 2017). Moreover if we consider the human body as the reference point, the term environment refers to the past and present environment and includes two dimensions: (1) the...

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

References

  1. Abondio P, Sazzini M, Garagnani P et al (2019) The genetic variability of APOE in different human populations and its implications for longevity. Genes 10:222.  https://doi.org/10.3390/genes10030222CrossRefGoogle Scholar
  2. Alvergne A, Jenkinson C, Faurie C (eds) (2016) Evolutionary thinking in medicine. Springer International Publishing, ChamGoogle Scholar
  3. Baines HL, Turnbull DM, Greaves LC (2014) Human stem cell aging: do mitochondrial DNA mutations have a causal role? Aging Cell 13:201–205.  https://doi.org/10.1111/acel.12199CrossRefGoogle Scholar
  4. Beirne C, Delahay R, Young A (2015) Sex differences in senescence: the role of intra-sexual competition in early adulthood. Proc R Soc B Biol Sci 282:20151086.  https://doi.org/10.1098/rspb.2015.1086CrossRefGoogle Scholar
  5. Bonafè M, Olivieri F, Cavallone L et al (2001) A gender – dependent genetic predisposition to produce high levels of IL-6 is detrimental for longevity. Eur J Immunol 31:2357–2361. https://doi.org/10.1002/1521-4141(200108)31:8<2357::AID-IMMU2357>3.0.CO;2-XGoogle Scholar
  6. Bonafè M, Barbieri M, Marchegiani F et al (2003) Polymorphic variants of insulin-like growth factor I (IGF-I) receptor and phosphoinositide 3-kinase genes affect IGF-I plasma levels and human longevity: cues for an evolutionarily conserved mechanism of life span control. J Clin Endocrinol Metab 88:3299–3304.  https://doi.org/10.1210/jc.2002-021810CrossRefGoogle Scholar
  7. Capri M, Santoro A, Garagnani P et al (2013) Genes of human longevity: an endless quest? Curr Vasc Pharmacol 12:707CrossRefGoogle Scholar
  8. Carter AJ, Nguyen AQ (2011) Antagonistic pleiotropy as a widespread mechanism for the maintenance of polymorphic disease alleles. BMC Med Genet 12:160.  https://doi.org/10.1186/1471-2350-12-160CrossRefGoogle Scholar
  9. Corella D, Ordovás JM (2014) Aging and cardiovascular diseases: the role of gene-diet interactions. Ageing Res Rev 18:53–73.  https://doi.org/10.1016/j.arr.2014.08.002CrossRefGoogle Scholar
  10. Corella D, Carrasco P, Sorlí JV et al (2013) Mediterranean diet reduces the adverse effect of the TCF7L2-rs7903146 polymorphism on cardiovascular risk factors and stroke incidence: a randomized controlled trial in a high-cardiovascular-risk population. Diabetes Care 36:3803–3811.  https://doi.org/10.2337/dc13-0955CrossRefGoogle Scholar
  11. Crespi BJ (2011) The emergence of human-evolutionary medical genomics. Evol Appl 4:292–314.  https://doi.org/10.1111/j.1752-4571.2010.00156.xCrossRefGoogle Scholar
  12. Dato S, Soerensen M, De Rango F et al (2018) The genetic component of human longevity: new insights from the analysis of pathway-based SNP-SNP interactions. Aging Cell 17:e12755.  https://doi.org/10.1111/acel.12755CrossRefGoogle Scholar
  13. Finkel T (2015) The metabolic regulation of aging. Nat Med 21:1416–1423.  https://doi.org/10.1038/nm.3998CrossRefGoogle Scholar
  14. Fortney K, Dobriban E, Garagnani P et al (2015) Genome-wide scan informed by age-related disease identifies loci for exceptional human longevity. PLoS Genet 11:e1005728.  https://doi.org/10.1371/journal.pgen.1005728CrossRefGoogle Scholar
  15. Franceschi C, Cossarizza A (1995) Introduction: the reshaping of the immune system with age. Int Rev Immunol 12:1–4.  https://doi.org/10.3109/08830189509056697CrossRefGoogle Scholar
  16. Franceschi C, Monti D, Sansoni P, Cossarizza A (1995) The immunology of exceptional individuals: the lesson of centenarians. Immunol Today 16:12–16CrossRefGoogle Scholar
  17. Franceschi C, Bonafè M, Valensin S et al (2000a) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254CrossRefGoogle Scholar
  18. Franceschi C, Valensin S, Bonafè M et al (2000b) The network and the remodeling theories of aging: historical background and new perspectives. Exp Gerontol 35:879–896CrossRefGoogle Scholar
  19. Garagnani P, Giuliani C, Pirazzini C et al (2013) Centenarians as super-controls to assess the biological relevance of genetic risk factors for common age-related diseases: a proof of principle on type 2 diabetes. Aging 5:373–385CrossRefGoogle Scholar
  20. Garagnani P, Pirazzini C, Giuliani C et al (2014) The three genetics (nuclear DNA, mitochondrial DNA, and gut microbiome) of longevity in humans considered as metaorganisms. Biomed Res Int 2014:e560340.  https://doi.org/10.1155/2014/560340CrossRefGoogle Scholar
  21. Garland T (2014) Trade-offs. Curr Biol 24:R60–R61.  https://doi.org/10.1016/j.cub.2013.11.036CrossRefGoogle Scholar
  22. Gavrilov LA, Gavrilova NS (2002) Evolutionary theories of aging and longevity. Sci World J 2:339–356.  https://doi.org/10.1100/tsw.2002.96CrossRefGoogle Scholar
  23. Giuliani C, Pirazzini C, Delledonne M et al (2017) Centenarians as extreme phenotypes: an ecological perspective to get insight into the relationship between the genetics of longevity and age-associated diseases. Mech Ageing Dev.  https://doi.org/10.1016/j.mad.2017.02.007CrossRefGoogle Scholar
  24. Giuliani C, Garagnani P, Franceschi C (2018) Genetics of human longevity within an eco-evolutionary nature-nurture framework. Circ Res 123:745–772.  https://doi.org/10.1161/CIRCRESAHA.118.312562CrossRefGoogle Scholar
  25. Goldsmith TC (2017) Evolvability, population benefit, and the evolution of programmed aging in mammals. Biochem Mosc 82:1423–1429.  https://doi.org/10.1134/S0006297917120021CrossRefGoogle Scholar
  26. Gorbunova V, Seluanov A, Mao Z, Hine C (2007) Changes in DNA repair during aging. Nucleic Acids Res 35:7466–7474.  https://doi.org/10.1093/nar/gkm756CrossRefGoogle Scholar
  27. Govindaraju D, Atzmon G, Barzilai N (2015) Genetics, lifestyle and longevity: lessons from centenarians. Appl Transl Genom 4:23–32.  https://doi.org/10.1016/j.atg.2015.01.001CrossRefGoogle Scholar
  28. Hartl FU, Bracher A, Hayer-Hartl M (2011) Molecular chaperones in protein folding and proteostasis. Nature 475:324–332.  https://doi.org/10.1038/nature10317CrossRefGoogle Scholar
  29. Hotamisligil GS (2010) Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 140:900–917.  https://doi.org/10.1016/j.cell.2010.02.034CrossRefGoogle Scholar
  30. Houle D, Govindaraju DR, Omholt S (2010) Phenomics: the next challenge. Nat Rev Genet 11:855–866.  https://doi.org/10.1038/nrg2897CrossRefGoogle Scholar
  31. Jaiswal S, Fontanillas P, Flannick J et al (2014) Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med 371:2488–2498.  https://doi.org/10.1056/NEJMoa1408617CrossRefGoogle Scholar
  32. Kennedy BK, Berger SL, Brunet A et al (2014) Geroscience: linking aging to chronic disease. Cell 159:709–713.  https://doi.org/10.1016/j.cell.2014.10.039CrossRefGoogle Scholar
  33. Kirkwood TBL (1977) Evolution of ageing. Nature 270:301–304.  https://doi.org/10.1038/270301a0CrossRefGoogle Scholar
  34. Kirkwood TBL, Holliday R (1979) The evolution of ageing and longevity. Proc R Soc Lond B Biol Sci 205:531–546.  https://doi.org/10.1098/rspb.1979.0083CrossRefGoogle Scholar
  35. Koga H, Kaushik S, Cuervo AM (2011) Protein homeostasis and aging: the importance of exquisite quality control. Ageing Res Rev 10:205–215.  https://doi.org/10.1016/j.arr.2010.02.001CrossRefGoogle Scholar
  36. Lemaitre J-F, Berger V, Bonenfant C et al (2015) Early-late life trade-offs and the evolution of ageing in the wild. Proc R Soc B Biol Sci 282:20150209.  https://doi.org/10.1098/rspb.2015.0209CrossRefGoogle Scholar
  37. López-Otín C, Blasco MA, Partridge L et al (2013) The hallmarks of aging. Cell 153:1194–1217.  https://doi.org/10.1016/j.cell.2013.05.039CrossRefGoogle Scholar
  38. Luis NM, Wang L, Ortega M et al (2016) Intestinal IRE1 is required for increased triglyceride metabolism and longer lifespan under dietary restriction. Cell Rep 17:1207–1216.  https://doi.org/10.1016/j.celrep.2016.10.003CrossRefGoogle Scholar
  39. Martin GM, Oshima J (2000) Lessons from human progeroid syndromes. Nature 408:263–266.  https://doi.org/10.1038/35041705CrossRefGoogle Scholar
  40. Mitteldorf JJ (2012) Adaptive aging in the context of evolutionary theory. Biochem Mosc 77:716–725.  https://doi.org/10.1134/S0006297912070036CrossRefGoogle Scholar
  41. Pal S, Tyler JK (2016) Epigenetics and aging. Sci Adv 2:e1600584.  https://doi.org/10.1126/sciadv.1600584CrossRefGoogle Scholar
  42. Parsons PA (1995) Inherited stress resistance and longevity: a stress theory of ageing. Heredity 75:216–221.  https://doi.org/10.1038/hdy.1995.126CrossRefGoogle Scholar
  43. Partridge L, Gems D (2002) Mechanisms of ageing: public or private? Nat Rev Genet 3:165–175.  https://doi.org/10.1038/nrg753CrossRefGoogle Scholar
  44. Powers ET, Balch WE (2013) Diversity in the origins of proteostasis networks – a driver for protein function in evolution. Nat Rev Mol Cell Biol 14:237–248.  https://doi.org/10.1038/nrm3542CrossRefGoogle Scholar
  45. Quintana-Murci L (2016) Understanding rare and common diseases in the context of human evolution. Genome Biol 17:225.  https://doi.org/10.1186/s13059-016-1093-yCrossRefGoogle Scholar
  46. Rando TA (2006) Stem cells, ageing and the quest for immortality. Nature 441:1080–1086.  https://doi.org/10.1038/nature04958CrossRefGoogle Scholar
  47. Riera CE, Dillin A (2015) Tipping the metabolic scales towards increased longevity in mammals. Nat Cell Biol 17:196–203.  https://doi.org/10.1038/ncb3107CrossRefGoogle Scholar
  48. Rodríguez JA, Marigorta UM, Hughes DA et al (2017) Antagonistic pleiotropy and mutation accumulation influence human senescence and disease. Nat Ecol Evol 1:0055.  https://doi.org/10.1038/s41559-016-0055CrossRefGoogle Scholar
  49. Su T, Turnbull D, Greaves L (2018) Roles of mitochondrial DNA mutations in stem cell ageing. Genes 9:182.  https://doi.org/10.3390/genes9040182CrossRefGoogle Scholar
  50. Suh Y, Atzmon G, Cho M-O et al (2008) Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc Natl Acad Sci 105: 3438–3442.  https://doi.org/10.1073/pnas.0705467105CrossRefGoogle Scholar
  51. Ukraintseva S, Yashin A, Arbeev K et al (2016) Puzzling role of genetic risk factors in human longevity: “risk alleles” as pro-longevity variants. Biogerontology 17:109–127.  https://doi.org/10.1007/s10522-015-9600-1CrossRefGoogle Scholar
  52. Vaidya A, Mao Z, Tian X et al (2014) Knock-in reporter mice demonstrate that DNA repair by non-homologous end joining declines with age. PLoS Genet 10:e1004511.  https://doi.org/10.1371/journal.pgen.1004511CrossRefGoogle Scholar
  53. van Exel E, Koopman JJE, Bodegom DV et al (2017) Effect of APOE ε4 allele on survival and fertility in an adverse environment. PLoS One e0179497:12.  https://doi.org/10.1371/journal.pone.0179497CrossRefGoogle Scholar
  54. Van Meter M, Kashyap M, Rezazadeh S et al (2014) SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age. Nat Commun 5:5011.  https://doi.org/10.1038/ncomms6011CrossRefGoogle Scholar
  55. Zeng Y, Nie C, Min J et al (2016) Novel loci and pathways significantly associated with longevity. Sci Rep 6.  https://doi.org/10.1038/srep21243
  56. Zhang H-S, Chen Y, Fan L et al (2015) The endoplasmic reticulum stress sensor IRE1α in intestinal epithelial cells is essential for protecting against colitis. J Biol Chem 290:15327–15336.  https://doi.org/10.1074/jbc.M114.633560CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Cristina Giuliani
    • 1
    • 2
    Email author
  • Paolo Garagnani
    • 3
  • Claudio Franceschi
    • 4
  1. 1.Laboratory of Molecular Anthropology & Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences (BiGeA)University of BolognaBolognaItaly
  2. 2.School of Anthropology and Museum EthnographyUniversity of OxfordOxfordUK
  3. 3.Department of Experimental, Diagnostic and Specialty Medicine (DIMES)University of BolognaBolognaItaly
  4. 4.IRCCS, Institute of Neurological Sciences of BolognaBolognaItaly

Section editors and affiliations

  • Diddahally R. Govindaraju
    • 1
    • 2
  1. 1.Department of Human Evolutionary Biology, Museum of Comparative ZoologyHarvard UniversityCambridgeUSA
  2. 2.The Institute for Aging Research, The Glenn Center for the Biology of Human AgingAlbert Einstein College of MedicineBronxUSA