Encyclopedia of Gerontology and Population Aging

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

Genomics of Aging and Longevity

  • Ghadeer Falah
  • Danielle Gutman
  • Gil AtzmonEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-69892-2_730-1

Synonyms

Definition

Genomics of aging and longevity encompasses the fields of genomics and epigenomics implemented towards the understanding of a healthy aging phenotype. Exceptionally long-lived individuals (centenarians) are used as a model for longevity alongside animal and cell models that are used for mechanism and pathway illustration and elucidation.

Overview

Aging can be defined as a progressive decline in organ function and is considered the main risk factor for chronic disease, weakened health, and increased risk of morality (Macedo et al. 2017). Aging research has progressed in recent years, especially since it has been found to be mediated, at least to some extent, by genetic pathways and biochemical processes (López-Otín et al. 2013). Further, longevity is one of the most complex phenotypes (Brooks-Wilson 2013) with studies centering on...

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

References

  1. Aquino EM, Benton MC, Haupt LM, Sutherland HG, Griffiths LR, Lea RA (2018) Current understanding of DNA methylation and age-related disease. OBM Genet 2:1–1CrossRefGoogle Scholar
  2. Armstrong NJ, Mather KA, Thalamuthu A et al (2017) Aging, exceptional longevity and comparisons of the Hannum and Horvath epigenetic clocks. Epigenomics.  https://doi.org/10.2217/epi-2016-0179CrossRefGoogle Scholar
  3. Axelrad MA, Atzmon G (2013) Epigenomic of aging. Genetics 2(1):e106.  https://doi.org/10.4172/2161-1041.1000e106CrossRefGoogle Scholar
  4. Beekman M, Blanché H, Perola M et al (2013) Genome-wide linkage analysis for human longevity: genetics of healthy aging study. Aging Cell.  https://doi.org/10.1111/acel.12039CrossRefGoogle Scholar
  5. Bergman A, Atzmon G, Ye K et al (2007) Buffering mechanisms in aging: a systems approach toward uncovering the genetic component of aging. PLoS Comput Biol 3(8):e170.  https://doi.org/10.1371/journal.pcbi.0030170CrossRefGoogle Scholar
  6. Bernstein BE, Mikkelsen TS, Xie X et al (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell.  https://doi.org/10.1016/j.cell.2006.02.041CrossRefGoogle Scholar
  7. Birney E, Smith GD, Greally JM (2016) Epigenome-wide association studies and the interpretation of disease -omics. PLoS Genet 12:e1006105CrossRefGoogle Scholar
  8. Biterge B, Schneider R (2014) Histone variants: key players of chromatin. Cell Tissue Res 356:457CrossRefGoogle Scholar
  9. Bjornsson HT, Sigurdsson MI, Fallin MD et al (2008) Intra-individual change over time in DNA methylation with familial clustering. JAMA.  https://doi.org/10.1001/jama.299.24.2877CrossRefGoogle Scholar
  10. Blacker TS, Duchen MR (2016) Investigating mitochondrial redox state using NADH and NADPH autofluorescence. Free Radic Biol Med 100:53CrossRefGoogle Scholar
  11. Bracken AP, Helin K (2009) Polycomb group proteins: navigators of lineage pathways led astray in cancer. Nat Rev Cancer 9:773CrossRefGoogle Scholar
  12. Broer L, Buchman AS, Deelen J et al (2015) GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy. J Gerontol A Biol Sci Med Sci.  https://doi.org/10.1093/gerona/glu166CrossRefGoogle Scholar
  13. Brooks-Wilson AR (2013) Genetics of healthy aging and longevity. Hum Genet 132:1323CrossRefGoogle Scholar
  14. Byun HM, Siegmund KD, Pan F et al (2009) Epigenetic profiling of somatic tissues from human autopsy specimens identifies tissue- and individual-specific DNA methylation patterns. Hum Mol Genet.  https://doi.org/10.1093/hmg/ddp445CrossRefGoogle Scholar
  15. Cao X, Dang W (2018) Histone modification changes during aging: cause or consequence? – what we have learned about epigenetic regulation of aging from model organisms. In: Epigenetics of aging and longevity. Academic, LondonGoogle Scholar
  16. Cardoso AL, Fernandes A, Aguilar-Pimentel JA et al (2018) Towards frailty biomarkers: candidates from genes and pathways regulated in aging and age-related diseases. Ageing Res Rev 47:214CrossRefGoogle Scholar
  17. Chen HP, Zhao YTZT (2015) Histone deacetylases and mechanisms of regulation of gene expression. Crit Rev Oncog 20:35CrossRefGoogle Scholar
  18. Drinkwater RD, Blake TJ, Morley AA, Turner DR (1989) Human lymphocytes aged in vivo have reduced levels of methylation in transcriptionally active and inactive DNA. Mutat Res DNAging.  https://doi.org/10.1016/0921-8734(89)90038-6CrossRefGoogle Scholar
  19. Erikson GA, Bodian DL, Rueda M et al (2016) Whole-Genome sequencing of a healthy aging cohort. Cell.  https://doi.org/10.1016/j.cell.2016.03.022CrossRefGoogle Scholar
  20. Fang EF, Scheibye-Knudsen M, Chua KF et al (2016) Nuclear DNA damage signalling to mitochondria in ageing. Nat Rev Mol Cell Biol 17:308CrossRefGoogle Scholar
  21. Ferri E, Gussago C, Casati M et al (2019) Apolipoprotein E gene in physiological and pathological aging. Mech Ageing Dev.  https://doi.org/10.1016/j.mad.2019.01.005CrossRefGoogle Scholar
  22. Field AE, Robertson NA, Wang T et al (2018) DNA methylation clocks in aging: categories, causes, and consequences. Mol Cell 71:882CrossRefGoogle Scholar
  23. Fraser J, Williamson I, Bickmore WA, Dostie J (2015) An overview of genome organization and how we got there: from FISH to Hi-C. Microbiol Mol Biol Rev.  https://doi.org/10.1128/mmbr.00006-15CrossRefGoogle Scholar
  24. Freudenberg-Hua Y, Freudenberg J, Vacic V et al (2014) Disease variants in genomes of 44 centenarians. Mol Genet Genomic Med.  https://doi.org/10.1002/mgg3.86CrossRefGoogle Scholar
  25. Fuke C, Shimabukuro M, Petronis A et al (2004) Age related changes in 5-methylcytosine content in human peripheral leukocytes and placentas: an HPLC-based study. Ann Hum Genet.  https://doi.org/10.1046/j.1529-8817.2004.00081.xCrossRefGoogle Scholar
  26. Gao W, Tan J, Hüls A et al (2017) Genetic variants associated with skin aging in the Chinese Han population. J Dermatol Sci.  https://doi.org/10.1016/j.jdermsci.2016.12.017CrossRefGoogle Scholar
  27. Ghirlando R, Felsenfeld G (2016) CTCF: making the right connections. Genes Dev 30:881CrossRefGoogle Scholar
  28. Gillette TG, Hill JA (2015) Readers, writers, and erasers: Chromatin as the whiteboard of heart disease. Circ Res 116:1245CrossRefGoogle Scholar
  29. Goldman RD, Shumaker DK, Erdos MR et al (2004) Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson–Gilford progeria syndrome. Proc Natl Acad Sci.  https://doi.org/10.1073/pnas.0402943101CrossRefGoogle Scholar
  30. Goll MG, Kirpekar F, Maggert KA, et al (2006) Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science (80-).  https://doi.org/10.1126/science.1120976CrossRefGoogle Scholar
  31. Gonzalo S (2010) Epigenetic alterations in aging. J Appl Physiol.  https://doi.org/10.1152/japplphysiol.00238.2010CrossRefGoogle Scholar
  32. Green DR, Galluzzi L, Kroemer G (2011) Mitochondria and the autophagy-inflammation-cell death axis in organismal aging. Science (80-) 333:1109CrossRefGoogle Scholar
  33. Grillari J, Grillari-Voglauer R (2010) Novel modulators of senescence, aging, and longevity: small non-coding RNAs enter the stage. Exp Gerontol 45:302CrossRefGoogle Scholar
  34. Gurinovich A, Bae H, Andersen S et al (2018) Ethnic-specific effect of Apoe alleles on extreme longevity. Innov Aging.  https://doi.org/10.1093/geroni/igy023.373CrossRefGoogle Scholar
  35. Hannum G, Guinney J, Zhao L et al (2013) Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell.  https://doi.org/10.1016/j.molcel.2012.10.016CrossRefGoogle Scholar
  36. Heshmati A (2018) Healthy aging as a solution to the ‘ticking time bomb’: dealing with aging population in urban china. Sociol Int J.  https://doi.org/10.15406/sij.2018.02.00038
  37. Heyn H, Li N, Ferreira HJ et al (2012) Distinct DNA methylomes of newborns and centenarians. Proc Natl Acad Sci.  https://doi.org/10.1073/pnas.1120658109CrossRefGoogle Scholar
  38. Hödl M, Basler K (2012) Transcription in the absence of histone H3.2 and H3K4 methylation. Curr Biol.  https://doi.org/10.1016/j.cub.2012.10.008CrossRefGoogle Scholar
  39. Holoch D, Moazed D (2015) RNA-mediated epigenetic regulation of gene expression. Nat Rev Genet 16:71CrossRefGoogle Scholar
  40. Horvath S (2013) DNA methylation age of human tissues and cell types. Genome Biol.  https://doi.org/10.1186/gb-2013-14-10-r115CrossRefGoogle Scholar
  41. Huan T, Chen G, Liu C et al (2018) Age-associated microRNA expression in human peripheral blood is associated with all-cause mortality and age-related traits. Aging Cell.  https://doi.org/10.1111/acel.12687CrossRefGoogle Scholar
  42. Huang F, Yi J, Zhou T et al (2017) Toward understanding non-coding RNA roles in intracranial aneurysms and subarachnoid hemorrhage. Transl Neurosci.  https://doi.org/10.1515/tnsci-2017-0010
  43. Ishimi Y, Masatoyo Kojima, Fujio Takeuchi, Terumasa Miyamoto, Masa-Atsu Yamada, Fumio Hanaoka (1987) Changes in chromatin structure during aging of human skin fibroblasts. Experimental Cell Research 169(2):458–467CrossRefGoogle Scholar
  44. Jin B, Li Y, Robertson KD (2011) DNA methylation: superior or subordinate in the epigenetic hierarchy? Genes Cancer 2:607CrossRefGoogle Scholar
  45. Jin F, Li Y, Dixon JR et al (2013) A high-resolution map of the three-dimensional chromatin interactome in human cells. Nature.  https://doi.org/10.1038/nature12644CrossRefGoogle Scholar
  46. Jintaridth P, Mutirangura A (2010) Distinctive patterns of age-dependent hypomethylation in interspersed repetitive sequences. Physiol Genomics.  https://doi.org/10.1152/physiolgenomics.00146.2009CrossRefGoogle Scholar
  47. Kauppila TES, Kauppila JHK, Larsson NG (2017) Mammalian mitochondria and aging: an update. Cell Metab 25:57CrossRefGoogle Scholar
  48. Kim S, Wyckoff J, Morris AT et al (2018) DNA methylation associated with healthy aging of elderly twins. GeroScience.  https://doi.org/10.1007/s11357-018-0040-0CrossRefGoogle Scholar
  49. Kronenberg F (2008) Genome-wide association studies in aging-related processes such as diabetes mellitus, atherosclerosis and cancer. Exp Gerontol 43:39CrossRefGoogle Scholar
  50. Lin E, Tsai SJ, Kuo PH et al (2017) The rs1277306 variant of the REST gene confers susceptibility to cognitive aging in an elderly Taiwanese population. Dement Geriatr Cogn Disord.  https://doi.org/10.1159/000455833
  51. Lipman T, Tiedje LB (2006) Epigenetic differences arise during the lifetime of monozygotic twins. MCN Am J Matern Child Nurs.  https://doi.org/10.1097/00005721-200605000-00016Google Scholar
  52. Lombard DB, Chua KF, Mostoslavsky R et al (2005) DNA repair, genome stability, and aging. Cell 120:497CrossRefGoogle Scholar
  53. López-Otín C, Blasco MA, Partridge L et al (2013) The hallmarks of aging. Cell.  https://doi.org/10.1016/j.cell.2013.05.039CrossRefGoogle Scholar
  54. Macedo JC, Vaz S, Logarinho E (2017) Mitotic dysfunction associated with aging hallmarks. Adv Exp Med Biol 1002:153CrossRefGoogle Scholar
  55. Mariño G, Niso-Santano M, Baehrecke EH, Kroemer G (2014) Self-consumption: the interplay of autophagy and apoptosis. Nat Rev Mol Cell Biol 15:81CrossRefGoogle Scholar
  56. Marta Kulis ME (2010) 2 – DNA methylation and cancer. ScienceDirect 70:27–56Google Scholar
  57. Massudi H, Grant R, Guillemin GJ, Braidy N (2012) NAD+ metabolism and oxidative stress: the golden nucleotide on a crown of thorns. Redox Rep.  https://doi.org/10.1179/1351000212y.0000000001CrossRefGoogle Scholar
  58. Mcclay JL, Aberg KA, Clark SL et al (2014) A methylome-wide study of aging using massively parallel sequencing of the methyl-CpG-enriched genomic fraction from blood in over 700 subjects. Hum Mol Genet.  https://doi.org/10.1093/hmg/ddt511CrossRefGoogle Scholar
  59. Mello CC, Conte D (2004) Revealing the world of RNA interference. Nature 431:338CrossRefGoogle Scholar
  60. Murabito JM, Yuan R, Lunetta KL (2012) The search for longevity and healthy aging genes: Insights from epidemiological studies and samples of long-lived individuals. J Gerontol Ser A Biol Sci Med Sci.  https://doi.org/10.1093/gerona/gls089CrossRefGoogle Scholar
  61. Noren Hooten N, Fitzpatrick M, Wood WH et al (2013) Age-related changes in microRNA levels in serum. Aging (Albany NY) 5:725CrossRefGoogle Scholar
  62. Oberdoerffer P, Michan S, McVay M, Mostoslavsky R, Vann J, Park SK, Hartlerode A, Stegmuller J, Hafner A, Loerch P, Wright SM, Mills KD, Bonni A, Yankner BA, Scully R, Prolla TA, Alt FW, Sinclair DA (2008) SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging. Cell 135:907CrossRefGoogle Scholar
  63. Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell.  https://doi.org/10.1016/S0092-8674(00)81656-6CrossRefGoogle Scholar
  64. Ooi SKT, Qiu C, Bernstein E et al (2007) DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature.  https://doi.org/10.1038/nature05987CrossRefGoogle Scholar
  65. Pegoraro G, Kubben N, Wickert U, Gohler H, Hoffmann K, Misteli T (2009) Ageing-related chromatin defects through loss of the NURD complex. Nat Cell Biol:1261–1267CrossRefGoogle Scholar
  66. Pérez RF, Tejedor JR, Bayón GF et al (2018) Distinct chromatin signatures of DNA hypomethylation in aging and cancer. Aging Cell.  https://doi.org/10.1111/acel.12744CrossRefGoogle Scholar
  67. Pickles S, Vigié P, Youle RJ (2018) Mitophagy and quality control mechanisms in mitochondrial maintenance. Curr Biol 28:R170CrossRefGoogle Scholar
  68. Pidsley R, Zotenko E, Peters TJ et al (2016) Critical evaluation of the Illumina MethylationEPIC BeadChip microarray for whole-genome DNA methylation profiling. Genome Biol.  https://doi.org/10.1186/s13059-016-1066-1
  69. Ruby JG, Wright KM, Rand KA et al (2018) Estimates of the heritability of human longevity are substantially inflated due to assortative mating. Genetics.  https://doi.org/10.1534/genetics.118.301613CrossRefGoogle Scholar
  70. Sathyan S, Barzilai N, Atzmon G et al (2018) Genetic insights into frailty: association of 9p21-23 locus with frailty. Front Med.  https://doi.org/10.3389/fmed.2018.00105
  71. Schübeler D (2015) Function and information content of DNA methylation. NatureGoogle Scholar
  72. Seddighi S, Varma VR, An Y et al (2018) SPARCL1 accelerates symptom onset in Alzheimer’s disease and influences brain structure and function during aging. J Alzheimers Dis.  https://doi.org/10.3233/JAD-170557CrossRefGoogle Scholar
  73. Sharma S, De Carvalho DD, Jeong S, Jones PA, Liang G (2011) Nucleosomes containing methylated DNA stabilize DNA methyltransferases 3A/3B and ensure faithful epigenetic inheritance. PLoS Genet 7:e1001286CrossRefGoogle Scholar
  74. Shumaker DK, Dechat T, Kohlmaier A et al (2006) Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. Proc Natl Acad Sci.  https://doi.org/10.1073/pnas.0602569103CrossRefGoogle Scholar
  75. Singh KK (2004) Mitochondrial dysfunction is a common phenotype in aging and cancer. Ann N Y Acad Sci 1019:260CrossRefGoogle Scholar
  76. Slieker RC, Relton CL, Gaunt TR et al (2018) Age-related DNA methylation changes are tissue-specific with ELOVL2 promoter methylation as exception. Epigenetics Chromatin.  https://doi.org/10.1186/s13072-018-0191-3
  77. Somel M, Guo S, Fu N et al (2010) MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain. Genome Res.  https://doi.org/10.1101/gr.106849.110CrossRefGoogle Scholar
  78. Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403:41CrossRefGoogle Scholar
  79. Sturmlechner I, Durik M, Sieben CJ et al (2017) Cellular senescence in renal ageing and disease. Nat Rev Nephrol.  https://doi.org/10.1038/nrneph.2016.183CrossRefGoogle Scholar
  80. Sundermann E, Levine A, Horvath S, Moore D (2018) Inflammation-related genes are associated with accelerated aging in HIV. Am J Geriatr Psychiatry 26:S118CrossRefGoogle Scholar
  81. Takeshima H, Yamashita S, Shimazu T et al (2009) The presence of RNA polymerase II, active or stalled, predicts epigenetic fate of promoter CpG islands. Genome Res.  https://doi.org/10.1101/gr.093310.109CrossRefGoogle Scholar
  82. Tasselli L, Zheng W, Chua KF (2017) SIRT6: novel mechanisms and links to aging and disease. Trends Endocrinol Metab 28:168CrossRefGoogle Scholar
  83. Theendakara V, Peters-Libeu CA, Bredesen DE, Rao RV (2018) Transcriptional effects of ApoE4: relevance to Alzheimer’s disease. Mol Neurobiol 55:5243CrossRefGoogle Scholar
  84. Unda SR, Villegas EA (2017) MicroRNA: a major key in pain neurobiology. Int J Cell Sci Mol Biol 3(5):555621.  https://doi.org/10.19080/ijcsmb.2017.03.555621CrossRefGoogle Scholar
  85. Vijg J, Dong X, Milholland B, Zhang L (2017) Genome instability: a conserved mechanism of ageing? Essays Biochem:305–315CrossRefGoogle Scholar
  86. Vijg J, Gravina S, Dong X (2018) Chapter 9 – Intratissue DNA methylation heterogeneity in aging. ScienceDirect 4:201–209Google Scholar
  87. Wang T, Zhang M, Jiang ZSE (2017) Mitochondrial dysfunction and ovarian aging. Am J Reprod Immunol 77:e12651CrossRefGoogle Scholar
  88. Wang Y, Yuan Q, Xie L (2018) Histone modifications in aging: the underlying mechanisms and implications. Curr Stem Cell Res Ther.  https://doi.org/10.2174/1574888x12666170817141921
  89. Warner HR (2005) Longevity genes: from primitive organisms to humans. Mech Ageing Dev 126(2):235CrossRefGoogle Scholar
  90. Wegman MP, Guo MH, Bennion DM et al (2014) Practicality of intermittent fasting in humans and its effect on oxidative stress and genes related to aging and metabolism. Rejuvenation Res.  https://doi.org/10.1089/rej.2014.1624CrossRefGoogle Scholar
  91. Westermann B (2012) Bioenergetic role of mitochondrial fusion and fission. Biochim Biophys Acta Bioenerg 1817:1833CrossRefGoogle Scholar
  92. Wilson VL, Jones PA (1983) DNA methylation decreases in aging but not in immortal cells. Science (80-).  https://doi.org/10.1126/science.6844925CrossRefGoogle Scholar
  93. Ye K et al (2013) Aging as accelerated accumulation of somatic variants: whole-genome sequencing of centenarian and middle-aged monozygotic twin pairs. Twin Res Hum Genet 16:1026–1032CrossRefGoogle Scholar
  94. Zhang W, Li J, Suzuki K, et al (2015) A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging. Science (80-).  https://doi.org/10.1126/science.aaa1356CrossRefGoogle Scholar
  95. Zhao N, Liu CC, Qiao W, Bu G (2018) Apolipoprotein E, receptors, and modulation of Alzheimer’s disease. Biol Psychiatry 83:347CrossRefGoogle Scholar
  96. Zirkel A, Nikolic M, Sofiadis K et al (2018) HMGB2 loss upon senescence entry disrupts genomic organization and induces CTCF clustering across cell types. Mol Cell.  https://doi.org/10.1016/j.molcel.2018.03.030CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Faculty of Natural ScienceUniversity of HaifaHaifaIsrael

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