Skip to main content
SpringerLink
Log in
Book cover

Models, Molecules and Mechanisms in Biogerontology pp 159–179Cite as

Attaining Epigenetic Rejuvenation: Challenges Ahead

  • Chapter
  • First Online:

  • 543 Accesses

Abstract

Recent studies from a number of model organisms have indicated that aging is mediated by genetic and epigenetic mechanisms. Few recent experiments also demonstrate that modulation in the chromatin modifying agents also affect the life span of an organism, and these chromatin modifications have a metabolic linkage. Further, the aging clock of an organism can be reset by reversal of aging. Aged cells can be reprogrammed to young ones by direct reprogramming by epigenetic rejuvenation or young cells can be obtained from them by passing through a dedifferentiated state. In the present report, we discuss the chromatin organization and its changes during aging. Further, we discuss how metabolic reprogramming can be linked to aging reversals to obtain epigenetic rejuvenation and challenges ahead.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Watson JD. Celebrating the genetic jubilee: a conversation with James D. Watson. Interviewed by John Rennie. Sci Am. 2003;288(4):66–9.

    Article  PubMed  Google Scholar 

  2. Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet. 2003;33(Suppl):245–54.

    Article  CAS  PubMed  Google Scholar 

  3. Weber CM, Henikoff S. Histone variants: dynamic punctuation in transcription. Genes Dev. 2014;28(7):672–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Sierra MI, Fernandez AF, Fraga MF. Epigenetics of aging. Curr Genomics. 2015;16(6):435–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ashok BT, Ali R. Aging research in India. Exp Gerontol. 2003;38(6):597–603.

    Article  PubMed  Google Scholar 

  6. Pyhtila MJ, Sherman FG. Age-associated studies on thermal stability and template effectiveness of DNA and nucleoproteins from beef thymus. Biochem Biophys Res Commun. 1968;31(3):340–4.

    Article  CAS  PubMed  Google Scholar 

  7. Medvedev ZA, Medvedeva MN, Robson L. Tissue specificity and age changes for the pattern of the H1 group of histones in chromatin from mouse tissues. Gerontology. 1978;24(4):286–92.

    Article  CAS  PubMed  Google Scholar 

  8. Tas S, Tam CF, Walford RL. Disulfide bonds and the structure of the chromatin complex in relation to aging. Mech Ageing Dev. 1980;12(1):65–80.

    Article  CAS  PubMed  Google Scholar 

  9. Chaturvedi MM, Kanungo MS. Analysis of conformation and function of the chromatin of the brain of young and old rats. Mol Biol Rep. 1985;10(4):215–9.

    CAS  PubMed  Google Scholar 

  10. Gravina S, Vijg J. Epigenetic factors in aging and longevity. Pflugers Archiv: European J Physiol. 2010;459(2):247–58.

    Article  CAS  Google Scholar 

  11. Benayoun BA, Pollina EA, Brunet A. Epigenetic regulation of ageing: linking environmental inputs to genomic stability. Nat Rev Mol Cell Biol. 2015;16(10):593–610.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Jin B, Li Y, Robertson KD. DNA methylation: superior or subordinate in the epigenetic hierarchy? Genes Cancer. 2011;2(6):607–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Klose RJ, Bird AP. Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci. 2006;31(2):89–97.

    Article  CAS  PubMed  Google Scholar 

  15. Pal S, Tyler JK. Epigenetics and aging. Sci Adv. 2016;2(7):e1600584.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Jung M, Pfeifer GP. Aging and DNA methylation. BMC Biol. 2015;13(7):1–8.

    CAS  Google Scholar 

  17. Watson JD, Baker TA, Bell SP, Gann A, Levine M, Losick R. Genome structure, chromatin, and the nucleosome Molecular Biology of the gene. 6th ed. Pearson: CSHL Press; 2008. p. 135–93.

    Google Scholar 

  18. Davey CA, Sargent DF, Luger K, Maeder AW, Richmond TJ. Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 a resolution. J Mol Biol. 2002;319(5):1097–113.

    Article  CAS  PubMed  Google Scholar 

  19. Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res. 2011;21(3):381–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature. 2009;462(7274):739–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Feser J, Truong D, Das C, Carson JJ, Kieft J, Harkness T, et al. Elevated histone expression promotes life span extension. Mol Cell. 2010;39(5):724–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Tsuchiya M, Dang N, Kerr EO, Hu D, Steffen KK, Oakes JA, et al. Sirtuin-independent effects of nicotinamide on lifespan extension from calorie restriction in yeast. Aging Cell. 2006;5(6):505–14.

    Article  CAS  PubMed  Google Scholar 

  23. Kanfi Y, Naiman S, Amir G, Peshti V, Zinman G, Nahum L, et al. The sirtuin SIRT6 regulates lifespan in male mice. Nature. 2012;483(7388):218–21.

    Article  CAS  PubMed  Google Scholar 

  24. Peleg S, Sananbenesi F, Zovoilis A, Burkhardt S, Bahari-Javan S, Agis-Balboa RC, et al. Altered histone acetylation is associated with age-dependent memory impairment in mice. Science. 2010;328(5979):753–6.

    Article  CAS  PubMed  Google Scholar 

  25. Larson K, Yan SJ, Tsurumi A, Liu J, Zhou J, Gaur K, et al. Heterochromatin formation promotes longevity and represses ribosomal RNA synthesis. PLoS Genet. 2012;8(1):e1002473.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wood JG, Hillenmeyer S, Lawrence C, Chang C, Hosier S, Lightfoot W, et al. Chromatin remodeling in the aging genome of Drosophila. Aging Cell. 2010;9(6):971–8.

    Article  CAS  PubMed  Google Scholar 

  27. Liu B, Wang Z, Zhang L, Ghosh S, Zheng H, Zhou Z. Depleting the methyltransferase Suv39h1 improves DNA repair and extends lifespan in a progeria mouse model. Nat Commun. 2013;4:1868.

    Article  PubMed  CAS  Google Scholar 

  28. Wang CM, Tsai SN, Yew TW, Kwan YW, Ngai SM. Identification of histone methylation multiplicities patterns in the brain of senescence-accelerated prone mouse 8. Biogerontology. 2010;11(1):87–102.

    Article  CAS  PubMed  Google Scholar 

  29. Ni Z, Ebata A, Alipanahiramandi E, Lee SS. Two SET domain containing genes link epigenetic changes and aging in Caenorhabditis elegans. Aging Cell. 2012;11(2):315–25.

    Article  CAS  PubMed  Google Scholar 

  30. Sen P, Dang W, Donahue G, Dai J, Dorsey J, Cao X, et al. H3K36 methylation promotes longevity by enhancing transcriptional fidelity. Genes Dev. 2015;29(13):1362–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. McCormick MA, Mason AG, Guyenet SJ, Dang W, Garza RM, Ting MK, et al. The SAGA histone deubiquitinase module controls yeast replicative lifespan via Sir2 interaction. Cell Rep. 2014;8(2):477–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Sharma R, Nakamura A, Takahashi R, Nakamoto H, Goto S. Carbonyl modification in rat liver histones: decrease with age and increase by dietary restriction. Free Radic Biol Med. 2006;40(7):1179–84.

    Article  CAS  PubMed  Google Scholar 

  33. Kosar M, Bartkova J, Hubackova S, Hodny Z, Lukas J, Bartek J. Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type- and insult-dependent manner and follow expression of p16(ink4a). Cell Cycle. 2011;10(3):457–68.

    Article  CAS  PubMed  Google Scholar 

  34. Cairns BR. Chromatin remodeling: insights and intrigue from single-molecule studies. Nat Struct Mol Biol. 2007;14(11):989–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Hargreaves DC, Crabtree GR. ATP-dependent chromatin remodeling: genetics, genomics and mechanisms. Cell Res. 2011;21(3):396–420.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Vaquero A, Loyola A, Reinberg D. The constantly changing face of chromatin. Sci Aging Knowledge Environ: SAGE KE. 2003;2003(14):RE4.

    Article  PubMed  Google Scholar 

  37. De Vaux V, Pfefferli C, Passannante M, Belhaj K, von Essen A, Sprecher SG, et al. The Caenorhabditis elegans LET-418/Mi2 plays a conserved role in lifespan regulation. Aging Cell. 2013;12(6):1012–20.

    Article  PubMed  CAS  Google Scholar 

  38. Dang W, Sutphin GL, Dorsey JA, Otte GL, Cao K, Perry RM, et al. Inactivation of yeast Isw2 chromatin remodeling enzyme mimics longevity effect of calorie restriction via induction of genotoxic stress response. Cell Metab. 2014;19(6):952–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Pegoraro G, Kubben N, Wickert U, Gohler H, Hoffmann K, Misteli T. Ageing-related chromatin defects through loss of the NURD complex. Nat Cell Biol. 2009;11(10):1261–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Henikoff S, Smith MM. Histone variants and epigenetics. Cold Spring Harb Perspect Biol. 2015;7(1):a019364.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Pina B, Suau P. Changes in histones H2A and H3 variant composition in differentiating and mature rat brain cortical neurons. Dev Biol. 1987;123(1):51–8.

    Article  CAS  PubMed  Google Scholar 

  42. Urban MK, Zweidler A. Changes in nucleosomal core histone variants during chicken development and maturation. Dev Biol. 1983;95(2):421–8.

    Article  CAS  PubMed  Google Scholar 

  43. Saade E, Pirozhkova I, Aimbetov R, Lipinski M, Ogryzko V. Molecular turnover, the H3.3 dilemma and organismal aging (hypothesis). Aging Cell. 2015;14(3):322–33.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Borghesan M, Fusilli C, Rappa F, Panebianco C, Rizzo G, Oben JA, et al. DNA Hypomethylation and histone variant macroH2A1 synergistically attenuate chemotherapy-induced senescence to promote hepatocellular carcinoma progression. Cancer Res. 2016;76(3):594–606.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Jeyapalan JC, Ferreira M, Sedivy JM, Herbig U. Accumulation of senescent cells in mitotic tissue of aging primates. Mech Ageing Dev. 2007;128(1):36–44.

    Article  CAS  PubMed  Google Scholar 

  46. Rinn JL, Chang HY. Genome regulation by long noncoding RNAs. Annu Rev Biochem. 2012;81:145–66.

    Article  CAS  PubMed  Google Scholar 

  47. Saka K, Ide S, Ganley AR, Kobayashi T. Cellular senescence in yeast is regulated by rDNA noncoding transcription. Curr Biol. 2013;23(18):1794–8.

    Article  CAS  PubMed  Google Scholar 

  48. Mori MA, Raghavan P, Thomou T, Boucher J, Robida-Stubbs S, Macotela Y, et al. Role of microRNA processing in adipose tissue in stress defense and longevity. Cell Metab. 2012;16(3):336–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ibanez-Ventoso C, Yang M, Guo S, Robins H, Padgett RW, Driscoll M. Modulated microRNA expression during adult lifespan in Caenorhabditis elegans. Aging Cell. 2006;5(3):235–46.

    Article  CAS  PubMed  Google Scholar 

  50. Kato M, Chen X, Inukai S, Zhao H, Slack FJ. Age-associated changes in expression of small, noncoding RNAs, including microRNAs, in C. elegans. RNA. 2011;17(10):1804–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Boehm M, Slack F. A developmental timing microRNA and its target regulate life span in C. elegans. Science. 2005;310(5756):1954–7.

    Article  CAS  PubMed  Google Scholar 

  52. de Lencastre A, Pincus Z, Zhou K, Kato M, Lee SS, Slack FJ. MicroRNAs both promote and antagonize longevity in C. elegans. Curr Biol. 2010;20(24):2159–68.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Szafranski K, Abraham KJ, Mekhail K. Non-coding RNA in neural function, disease, and aging. Front Genet. 2015;6:87.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Liu N, Landreh M, Cao K, Abe M, Hendriks GJ, Kennerdell JR, et al. The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila. Nature. 2012;482(7386):519–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Lee J, Padhye A, Sharma A, Song G, Miao J, Mo YY, et al. A pathway involving farnesoid X receptor and small heterodimer partner positively regulates hepatic sirtuin 1 levels via microRNA-34a inhibition. J Biol Chem. 2010;285(17):12604–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Jung HJ, Suh Y. MicroRNA in aging: from discovery to biology. Curr Genomics. 2012;13(7):548–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Meier I, Fellini L, Jakovcevski M, Schachner M, Morellini F. Expression of the snoRNA host gene gas5 in the hippocampus is upregulated by age and psychogenic stress and correlates with reduced novelty-induced behavior in C57BL/6 mice. Hippocampus. 2010;20(9):1027–36.

    Article  CAS  PubMed  Google Scholar 

  58. Castel SE, Martienssen RA. RNA interference in the nucleus: roles for small RNAs in transcription, epigenetics and beyond. Nat Rev Genet. 2013;14(2):100–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Allis CD, Bowen JK, Abraham GN, Glover CV, Gorovsky MA. Proteolytic processing of histone H3 in chromatin: a physiologically regulated event in Tetrahymena micronuclei. Cell. 1980;20(1):55–64.

    Article  CAS  PubMed  Google Scholar 

  60. Purohit JS, Chaturvedi MM, Panda P. Histone protease: the tale of tail clippers. Int J Integr Sci, Innov Technol. 2012;1(1):51–60.

    CAS  Google Scholar 

  61. Lin R, Cook RG, Allis CD. Proteolytic removal of core histone amino termini and dephosphorylation of histone H1 correlate with the formation of condensed chromatin and transcriptional silencing during Tetrahymena macronuclear development. Genes Dev. 1991;5(9):1601–10.

    Article  CAS  PubMed  Google Scholar 

  62. Satchidananda PJ, Mohan CM. Chromatin and aging. In: Rath PS PC, Sharma S, editors. Topics in biomedical gerontology. Singapore: Springer; 2017. p. 205.

    Google Scholar 

  63. Mahendra G, Gupta S, Kanungo MS. Effect of 17beta estradiol and progesterone on the conformation of the chromatin of the liver of female Japanese quail during aging. Arch Gerontol Geriatr. 1999;28(2):149–58.

    Article  CAS  PubMed  Google Scholar 

  64. Mahendra G, Kanungo MS. Age-related and steroid induced changes in the histones of the quail liver. Arch Gerontol Geriatr. 2000;30(2):109–14.

    Article  CAS  PubMed  Google Scholar 

  65. Panda P, Chaturvedi MM, Panda AK, Suar M, Purohit JS. Purification and characterization of a novel histone H2A specific protease (H2Asp) from chicken liver nuclear extract. Gene. 2013;512(1):47–54.

    Article  CAS  PubMed  Google Scholar 

  66. Purohit JS, Tomar RS, Panigrahi AK, Pandey SM, Singh D, Chaturvedi MM. Chicken liver glutamate dehydrogenase (GDH) demonstrates a histone H3 specific protease (H3ase) activity in vitro. Biochimie. 2013;95(11):1999–2009.

    Article  CAS  PubMed  Google Scholar 

  67. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324(5930):1029–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Barzilai N, Huffman DM, Muzumdar RH, Bartke A. The critical role of metabolic pathways in aging. Diabetes. 2012;61(6):1315–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Bratic I, Trifunovic A. Mitochondrial energy metabolism and ageing. Biochim Biophys Acta. 2010;1797(6–7):961–7.

    Article  CAS  PubMed  Google Scholar 

  70. Ward PS, Patel J, Wise DR, Abdel-Wahab O, Bennett BD, Coller HA, et al. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell. 2010;17(3):225–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Pan M, Reid MA, Lowman XH, Kulkarni RP, Tran TQ, Liu X, et al. Regional glutamine deficiency in tumours promotes dedifferentiation through inhibition of histone demethylation. Nat Cell Biol. 2016;18(10):1090–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Chowdhury R, Yeoh KK, Tian YM, Hillringhaus L, Bagg EA, Rose NR, et al. The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases. EMBO Rep. 2011;12(5):463–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Bowling AC, Schulz JB, Brown RH Jr, Beal MF. Superoxide dismutase activity, oxidative damage, and mitochondrial energy metabolism in familial and sporadic amyotrophic lateral sclerosis. J Neurochem. 1993;61(6):2322–5.

    Article  CAS  PubMed  Google Scholar 

  74. Hagen TM, Yowe DL, Bartholomew JC, Wehr CM, Do KL, Park JY, et al. Mitochondrial decay in hepatocytes from old rats: membrane potential declines, heterogeneity and oxidants increase. Proc Natl Acad Sci U S A. 1997;94(7):3064–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Wallace DC, Fan W, Procaccio V. Mitochondrial energetics and therapeutics. Annu Rev Pathol. 2010;5:297–348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Koopman WJ, Willems PH, Smeitink JA. Monogenic mitochondrial disorders. N Engl J Med. 2012;366(12):1132–41.

    Article  CAS  PubMed  Google Scholar 

  77. Bratic A, Larsson NG. The role of mitochondria in aging. J Clin Invest. 2013;123(3):951–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Sun N, Youle RJ, Finkel T. The mitochondrial basis of aging. Mol Cell. 2016;61(5):654–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011;13(2):132–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Ren J, Pulakat L, Whaley-Connell A, Sowers JR. Mitochondrial biogenesis in the metabolic syndrome and cardiovascular disease. J Mol Med. 2010;88(10):993–1001.

    Article  CAS  PubMed  Google Scholar 

  81. Turner N, Heilbronn LK. Is mitochondrial dysfunction a cause of insulin resistance? Trends Endocrinol Metab. 2008;19(9):324–30.

    Article  CAS  PubMed  Google Scholar 

  82. Su B, Wang X, Zheng L, Perry G, Smith MA, Zhu X. Abnormal mitochondrial dynamics and neurodegenerative diseases. Biochim Biophys Acta. 2010;1802(1):135–42.

    Article  CAS  PubMed  Google Scholar 

  83. Mammucari C, Rizzuto R. Signaling pathways in mitochondrial dysfunction and aging. Mech Ageing Dev. 2010;131(7–8):536–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Verdin E. NAD(+) in aging, metabolism, and neurodegeneration. Science. 2015;350(6265):1208–13.

    Article  CAS  PubMed  Google Scholar 

  85. Scheibye-Knudsen M, Mitchell SJ, Fang EF, Iyama T, Ward T, Wang J, et al. A high-fat diet and NAD(+) activate Sirt1 to rescue premature aging in cockayne syndrome. Cell Metab. 2014;20(5):840–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. German NJ, Haigis MC. Sirtuins and the metabolic hurdles in Cancer. Curr Biol. 2015;25(13):R569–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Vassilopoulos A, Fritz KS, Petersen DR, Gius D. The human sirtuin family: evolutionary divergences and functions. Hum Genomics. 2011;5(5):485–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Madeo F, Zimmermann A, Maiuri MC, Kroemer G. Essential role for autophagy in life span extension. J Clin Invest. 2015;125(1):85–93.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science. 2009;325(5937):201–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Fontana L, Partridge L, Longo VD. Extending healthy life span--from yeast to humans. Science. 2010;328(5976):321–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Wang L, Karpac J, Jasper H. Promoting longevity by maintaining metabolic and proliferative homeostasis. J Exp Biol. 2014;217(Pt 1):109–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Lee CK, Allison DB, Brand J, Weindruch R, Prolla TA. Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts. Proc Natl Acad Sci U S A. 2002;99(23):14988–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Higami Y, Pugh TD, Page GP, Allison DB, Prolla TA, Weindruch R. Adipose tissue energy metabolism: altered gene expression profile of mice subjected to long-term caloric restriction. FASEB J: Off Pub Fed Am Soc Exp Biol. 2004;18(2):415–7.

    Article  CAS  Google Scholar 

  94. Higami Y, Barger JL, Page GP, Allison DB, Smith SR, Prolla TA, et al. Energy restriction lowers the expression of genes linked to inflammation, the cytoskeleton, the extracellular matrix, and angiogenesis in mouse adipose tissue. J Nutr. 2006;136(2):343–52.

    Article  CAS  PubMed  Google Scholar 

  95. Weindruch R, Walford RL, Fligiel S, Guthrie D. The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. J Nutr. 1986;116(4):641–54.

    Article  CAS  PubMed  Google Scholar 

  96. Anderson RM, Weindruch R. Metabolic reprogramming in dietary restriction. Interdiscip Top Gerontol. 2007;35:18–38.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Solon-Biet SM, Mitchell SJ, Coogan SC, Cogger VC, Gokarn R, McMahon AC, et al. Dietary protein to carbohydrate ratio and caloric restriction: comparing metabolic outcomes in mice. Cell Rep. 2015;11(10):1529–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Solon-Biet SM, McMahon AC, Ballard JW, Ruohonen K, Wu LE, Cogger VC, et al. The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. Cell Metab. 2014;19(3):418–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Charville GW, Rando TA. Stem cell ageing and non-random chromosome segregation. Philos Trans R Soc Lond Ser B Biol Sci. 2011;366(1561):85–93.

    Article  CAS  Google Scholar 

  100. Kimura KD, Tissenbaum HA, Liu Y, Ruvkun G. Daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science. 1997;277(5328):942–6.

    Article  CAS  PubMed  Google Scholar 

  101. Kapahi P, Zid BM, Harper T, Koslover D, Sapin V, Benzer S. Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol. 2004;14(10):885–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Apfeld J, O'Connor G, McDonagh T, DiStefano PS, Curtis R. The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans. Genes Dev. 2004;18(24):3004–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Fielenbach N, Antebi A. C. elegans dauer formation and the molecular basis of plasticity. Genes Dev. 2008;22(16):2149–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Sallon S, Solowey E, Cohen Y, Korchinsky R, Egli M, Woodhatch I, et al. Germination, genetics, and growth of an ancient date seed. Science. 2008;320(5882):1464.

    Article  CAS  PubMed  Google Scholar 

  105. Cano RJ, Borucki MK. Revival and identification of bacterial spores in 25- to 40-million-year-old Dominican amber. Science. 1995;268(5213):1060–4.

    Article  CAS  PubMed  Google Scholar 

  106. Rando TA, Chang HY. Aging, rejuvenation, and epigenetic reprogramming: resetting the aging clock. Cell. 2012;148(1–2):46–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Briggs R, King TJ. Transplantation of living nuclei from blastula cells into enucleated Frogs' eggs. Proc Natl Acad Sci U S A. 1952;38(5):455–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Gurdon JB. The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. J Embryol Exp Morphol. 1962;10:622–40.

    CAS  PubMed  Google Scholar 

  109. Campbell KH, McWhir J, Ritchie WA, Wilmut I. Sheep cloned by nuclear transfer from a cultured cell line. Nature. 1996;380(6569):64–6.

    Article  CAS  PubMed  Google Scholar 

  110. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–76.

    Article  CAS  PubMed  Google Scholar 

  111. Stadtfeld M, Hochedlinger K. Induced pluripotency: history, mechanisms, and applications. Genes Dev. 2010;24(20):2239–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Rossant J. Stem cells from the mammalian blastocyst. Stem Cells. 2001;19(6):477–82.

    Article  CAS  PubMed  Google Scholar 

  113. Loh KM, Lim B. Recreating pluripotency? Cell Stem Cell. 2010;7(2):137–9.

    Article  CAS  PubMed  Google Scholar 

  114. Bunster E, Meyer RK. An improved method of parabiosis. Anat Rec. 1933;57(4):339–43.

    Article  Google Scholar 

  115. Conboy IM, Conboy MJ, Wagers AJ, Girma ER, Weissman IL, Rando TA. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature. 2005;433(7027):760–4.

    Article  CAS  PubMed  Google Scholar 

  116. Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G, et al. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature. 2011;477(7362):90–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Adler AS, Sinha S, Kawahara TL, Zhang JY, Segal E, Chang HY. Motif module map reveals enforcement of aging by continual NF-kappaB activity. Genes Dev. 2007;21(24):3244–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009;460(7253):392–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Chen C, Liu Y, Liu Y, Zheng P. mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells. Sci Signaling. 2009;2(98):ra75.

    Article  Google Scholar 

  120. Feng S, Jacobsen SE, Reik W. Epigenetic reprogramming in plant and animal development. Science. 2010;330(6004):622–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Meissner A. Epigenetic modifications in pluripotent and differentiated cells. Nat Biotechnol. 2010;28(10):1079–88.

    Article  CAS  PubMed  Google Scholar 

  122. Mikkelsen TS, Hanna J, Zhang X, Ku M, Wernig M, Schorderet P, et al. Dissecting direct reprogramming through integrative genomic analysis. Nature. 2008;454(7200):49–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Vastenhouw NL, Zhang Y, Woods IG, Imam F, Regev A, Liu XS, et al. Chromatin signature of embryonic pluripotency is established during genome activation. Nature. 2010;464(7290):922–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Creyghton MP, Cheng AW, Welstead GG, Kooistra T, Carey BW, Steine EJ, et al. Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci U S A. 2010;107(50):21931–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Krizhanovsky V, Lowe SW. Stem cells: the promises and perils of p53. Nature. 2009;460(7259):1085–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Greer EL, Maures TJ, Ucar D, Hauswirth AG, Mancini E, Lim JP, et al. Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans. Nature. 2011;479(7373):365–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Narita M, Nunez S, Heard E, Narita M, Lin AW, Hearn SA, et al. Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell. 2003;113(6):703–16.

    Article  CAS  PubMed  Google Scholar 

  128. Van Den Bogaert A, De Zutter S, Heyrman L, Mendlewicz J, Adolfsson R, Van Broeckhoven C, et al. Response to Zhang et al (2005): loss-of-function mutation in tryptophan hydroxylase-2 identified in unipolar major Depression. Neuron 45, 11–16. Neuron. 2005;48(5):704; author reply 5-6.

    Google Scholar 

  129. Gao S, Chung YG, Parseghian MH, King GJ, Adashi EY, Latham KE. Rapid H1 linker histone transitions following fertilization or somatic cell nuclear transfer: evidence for a uniform developmental program in mice. Dev Biol. 2004;266(1):62–75.

    Article  CAS  PubMed  Google Scholar 

  130. Apostolou E, Hochedlinger K. Chromatin dynamics during cellular reprogramming. Nature. 2013;502(7472):462–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Lapasset L, Milhavet O, Prieur A, Besnard E, Babled A, Ait-Hamou N, et al. Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state. Genes Dev. 2011;25(21):2248–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Li H, Collado M, Villasante A, Strati K, Ortega S, Canamero M, et al. The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature. 2009;460(7259):1136–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Mahmoudi S, Brunet A. Aging and reprogramming: a two-way street. Curr Opin Cell Biol. 2012;24(6):744–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Kim K, Doi A, Wen B, Ng K, Zhao R, Cahan P, et al. Epigenetic memory in induced pluripotent stem cells. Nature. 2010;467(7313):285–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cluster Innovation Centre, University Stadium, G.C. Narang Marg, North Campus, Delhi University, Delhi, India

    Jogeswar S. Purohit

  2. Laboratory for Chromatin Biology, Department of Zoology, University of Delhi, Delhi, India

    Neetika Singh, Shah S. Hussain & Madan M. Chaturvedi

Authors
  1. Jogeswar S. Purohit
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Neetika Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shah S. Hussain
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Madan M. Chaturvedi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Madan M. Chaturvedi .

Editor information

Editors and Affiliations

  1. School of Life Sciences, Jawaharlal Nehru University, New Delhi, India

    Pramod C. Rath

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Purohit, J.S., Singh, N., Hussain, S.S., Chaturvedi, M.M. (2020). Attaining Epigenetic Rejuvenation: Challenges Ahead. In: Rath, P. (eds) Models, Molecules and Mechanisms in Biogerontology. Springer, Singapore. https://doi.org/10.1007/978-981-32-9005-1_9

Download citation

Publish with us

Policies and ethics

Search

Navigation