Abstract
Aging is a complex trait and is influenced by multiple factors that are both intrinsic and extrinsic to the organism (Kirkwood et al. 2000; Knight 2000). Efforts to understanding the mechanisms that extend or shorten lifespan have been made since the early twentieth century. Aging is characteristically associated with a progressive decline in the overall fitness of the organism. Several studies have provided valuable information about the molecular events that accompany this process and include accumulation of nuclear and mitochondrial mutations, shortened and dysfunctional telomeres, oxidative damage of protein/DNA, senescence and apoptosis (Muller 2009). Clinical studies and work on model organisms have shown that there is an increased susceptibility to conditions such as neurological disorders, diabetes, cardiovascular diseases, degenerative syndromes and even cancers, with age (Arvanitakis et al. 2006; Lee and Kim 2006; Rodriguez and Fraga 2010).
Asmitha Lazarus and Kushal Kr. Banerjee have contributed equally
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Adams PD (2009) Healing and hurting: molecular mechanisms, functions, and pathologies of cellular senescence. Mol Cell 36:2–14
Agrelo R, Setien F, Espada J, Artiga MJ, Rodriguez M, Perez-Rosado A, Sanchez-Aguilera A, Fraga MF, Piris MA, Esteller M (2005) Inactivation of the lamin A/C gene by CpG island promoter hypermethylation in hematologic malignancies, and its association with poor survival in nodal diffuse large B-cell lymphoma. J Clin Oncol 23:3940–3947
Arvanitakis Z, Wilson RS, Bennett DA (2006) Diabetes mellitus, dementia, and cognitive function in older persons. J Nutr Health Aging 10:287–291
Bandyopadhyay D, Okan NA, Bales E, Nascimento L, Cole PA, Medrano EE (2002) Down-regulation of p300/CBP histone acetyltransferase activates a senescence checkpoint in human melanocytes. Cancer Res 62:6231–6239
Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Res 21:381–395
Bartkova J, Rezaei N, Liontos M, Karakaidos P, Kletsas D, Issaeva N, Vassiliou LV, Kolettas E, Niforou K, Zoumpourlis VC, Takaoka M, Nakagawa H, Tort F, Fugger K, Johansson F, Sehested M, Andersen CL, Dyrskjot L, Orntoft T, Lukas J, Kittas C, Helleday T, Halazonetis TD, Bartek J, Gorgoulis VG (2006) Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 444:633–637
Bassett A, Cooper S, Wu C, Travers A (2009) The folding and unfolding of eukaryotic chromatin. Curr Opin Genet Dev 19:159–165
Bates DJ, Liang R, Li N, Wang E (2009) The impact of noncoding RNA on the biochemical and molecular mechanisms of aging. Biochim Biophys Acta 1790:970–979
Bates DJ, Li N, Liang R, Sarojini H, An J, Masternak MM, Bartke A, Wang E (2010) MicroRNA regulation in Ames dwarf mouse liver may contribute to delayed aging. Aging Cell 9:1–18
Ben-Porath I, Weinberg RA (2005) The signals and pathways activating cellular senescence. Int J Biochem Cell Biol 37:961–976
Blais A, van Oevelen CJ, Margueron R, Acosta-Alvear D, Dynlacht BD (2007) Retinoblastoma tumor suppressor protein-dependent methylation of histone H3 lysine 27 is associated with irreversible cell cycle exit. J Cell Biol 179:1399–1412
Boehm M, Slack F (2005) A developmental timing microRNA and its target regulate life span in C. elegans. Science 310:1954–1957
Bommi PV, Dimri M, Sahasrabuddhe AA, Khandekar J, Dimri GP (2010) The polycomb group protein BMI1 is a transcriptional target of HDAC inhibitors. Cell Cycle 9:2663–2673
Bonasio R, Tu S, Reinberg D (2010) Molecular signals of epigenetic states. Science 330:612–616
Bork S, Pfister S, Witt H, Horn P, Korn B, Ho AD, Wagner W (2010) DNA methylation pattern changes upon long-term culture and aging of human mesenchymal stromal cells. Aging Cell 9:54–63
Bornman DM, Mathew S, Alsruhe J, Herman JG, Gabrielson E (2001) Methylation of the E-cadherin gene in bladder neoplasia and in normal urothelial epithelium from elderly individuals. Am J Pathol 159:831–835
Bracken AP, Kleine-Kohlbrecher D, Dietrich N, Pasini D, Gargiulo G, Beekman C, Theilgaard-Monch K, Minucci S, Porse BT, Marine JC, Hansen KH, Helin K (2007) The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes Dev 21:525–530
Braig M, Schmitt CA (2006) Oncogene-induced senescence: putting the brakes on tumor development. Cancer Res 66:2881–2884
Braig M, Lee S, Loddenkemper C, Rudolph C, Peters AH, Schlegelberger B, Stein H, Dorken B, Jenuwein T, Schmitt CA (2005) Oncogene-induced senescence as an initial barrier in lymphoma development. Nature 436:660–665
Brooks CL, Gu W (2008) p53 Activation: a case against Sir. Cancer Cell 13:377–378
Cao R, Tsukada Y, Zhang Y (2005) Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol Cell 20:845–854
Casillas MA Jr, Lopatina N, Andrews LG, Tollefsbol TO (2003) Transcriptional control of the DNA methyltransferases is altered in aging and neoplastically-transformed human fibroblasts. Mol Cell Biochem 252:33–43
Chen LH, Chiou GY, Chen YW, Li HY, Chiou SH (2010) MicroRNA and aging: a novel modulator in regulating the aging network. Ageing Res Rev 9(Suppl 1):S59–S66
Chouliaras L, van den Hove DL, Kenis G, Dela Cruz J, Lemmens MA, van Os J, Steinbusch HW, Schmitz C, Rutten BP (2011a) Caloric restriction attenuates age-related changes of DNA methyltransferase 3a in mouse hippocampus. Brain Behav Immun 25:616–623
Chouliaras L, van den Hove DL, Kenis G, Keitel S, Hof PR, van Os J, Steinbusch HW, Schmitz C, Rutten BP (2011b) Prevention of age-related changes in hippocampal levels of 5-methylcytidine by caloric restriction. Neurobiol Aging 33(8):1672–1681
Christensen BC, Houseman EA, Marsit CJ, Zheng S, Wrensch MR, Wiemels JL, Nelson HH, Karagas MR, Padbury JF, Bueno R, Sugarbaker DJ, Yeh RF, Wiencke JK, Kelsey KT (2009) Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet 5:e1000602
Chuang JY, Hung JJ (2011) Overexpression of HDAC1 induces cellular senescence by Sp1/PP2A/pRb pathway. Biochem Biophys Res Commun 407:587–592
Costanzi C, Pehrson JR (1998) Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals. Nature 393:599–601
Dang W, Steffen KK, Perry R, Dorsey JA, Johnson FB, Shilatifard A, Kaeberlein M, Kennedy BK, Berger SL (2009) Histone H4 lysine 16 acetylation regulates cellular lifespan. Nature 459:802–807
De Carvalho DD, You JS, Jones PA (2010) DNA methylation and cellular reprogramming. Trends Cell Biol 20:609–617
Dechat T, Pfleghaar K, Sengupta K, Shimi T, Shumaker DK, Solimando L, Goldman RD (2008) Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin. Genes Dev 22:832–853
Deng CX (2009) SIRT1, is it a tumor promoter or tumor suppressor? Int J Biol Sci 5:147–152
DePinho RA (2000) The age of cancer. Nature 408:248–254
Dimauro T, David G (2009) Chromatin modifications: the driving force of senescence and aging? Aging (Albany NY) 1:182–190
Fairweather DS, Fox M, Margison GP (1987) The in vitro lifespan of MRC-5 cells is shortened by 5-azacytidine-induced demethylation. Exp Cell Res 168:153–159
Feser J, Tyler J (2011) Chromatin structure as a mediator of aging. FEBS Lett 585:2041–2048
Fraga MF, Esteller M (2007) Epigenetics and aging: the targets and the marks. Trends Genet 23:413–418
Frankel S, Rogina B (2005) Drosophila longevity is not affected by heterochromatin-mediated gene silencing. Aging Cell 4:53–56
Frenster JH, Allfrey VG, Mirsky AE (1963) Repressed and active chromatin isolated from interphase lymphocytes. Proc Natl Acad Sci U S A 50:1026–1032
Fujita N, Watanabe S, Ichimura T, Ohkuma Y, Chiba T, Saya H, Nakao M (2003) MCAF mediates MBD1-dependent transcriptional repression. Mol Cell Biol 23:2834–2843
Fuke C, Shimabukuro M, Petronis A, Sugimoto J, Oda T, Miura K, Miyazaki T, Ogura C, Okazaki Y, Jinno Y (2004) Age related changes in 5-methylcytosine content in human peripheral leukocytes and placentas: an HPLC-based study. Ann Hum Genet 68:196–204
Funayama R, Saito M, Tanobe H, Ishikawa F (2006) Loss of linker histone H1 in cellular senescence. J Cell Biol 175:869–880
Gao Z, Xu MS, Barnett TL, Xu CW (2011) Resveratrol induces cellular senescence with attenuated mono-ubiquitination of histone H2B in glioma cells. Biochem Biophys Res Commun 407:271–276
Geiman TM, Muegge K (2010) DNA methylation in early development. Mol Reprod Dev 77:105–113
Ghosh S, George S, Roy U, Ramachandran D, Kolthur-Seetharam U (2010) NAD: a master regulator of transcription. Biochim Biophys Acta 1799:681–693
Gibney ER, Nolan CM (2010) Epigenetics and gene expression. Heredity 105:4–13
Goldman RD, Shumaker DK, Erdos MR, Eriksson M, Goldman AE, Gordon LB, Gruenbaum Y, Khuon S, Mendez M, Varga R, Collins FS (2004) Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci U S A 101:8963–8968
Gorospe M, Abdelmohsen K (2011) MicroRegulators come of age in senescence. Trends Genet 27:233–241
Gotta M, Strahl-Bolsinger S, Renauld H, Laroche T, Kennedy BK, Grunstein M, Gasser SM (1997) Localization of Sir2p: the nucleolus as a compartment for silent information regulators. EMBO J 16:3243–3255
Grandinetti KB, Jelinic P, DiMauro T, Pellegrino J, Fernandez Rodriguez R, Finnerty PM, Ruoff R, Bardeesy N, Logan SK, David G (2009) Sin3B expression is required for cellular senescence and is up-regulated upon oncogenic stress. Cancer Res 69:6430–6437
Gregoire S, Xiao L, Nie J, Zhang X, Xu M, Li J, Wong J, Seto E, Yang XJ (2007) Histone deacetylase 3 interacts with and deacetylates myocyte enhancer factor 2. Mol Cell Biol 27:1280–1295
Grillari J, Grillari-Voglauer R (2010) Novel modulators of senescence, aging, and longevity: small non-coding RNAs enter the stage. Exp Gerontol 45:302–311
Ha CW, Huh WK (2011) The implication of Sir2 in replicative aging and senescence in Saccharomyces cerevisiae. Aging (Albany NY) 3:319–324
Hajji N, Wallenborg K, Vlachos P, Fullgrabe J, Hermanson O, Joseph B (2010) Opposing effects of hMOF and SIRT1 on H4K16 acetylation and the sensitivity to the topoisomerase II inhibitor etoposide. Oncogene 29:2192–2204
Hans F, Dimitrov S (2001) Histone H3 phosphorylation and cell division. Oncogene 20:3021–3027
Hayflick L (1965) The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 37:614–636
He L, Hannon GJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5:522–531
He H, Yu FX, Sun C, Luo Y (2011) CBP/p300 and SIRT1 are involved in transcriptional regulation of S-phase specific histone genes. PLoS One 6:e22088
Herbig U, Ferreira M, Condel L, Carey D, Sedivy JM (2006) Cellular senescence in aging primates. Science 311:1257
Hoal-van Helden EG, van Helden PD (1989) Age-related methylation changes in DNA may reflect the proliferative potential of organs. Mutat Res 219:263–266
Hock R, Furusawa T, Ueda T, Bustin M (2007) HMG chromosomal proteins in development and disease. Trends Cell Biol 17:72–79
Hornsby PJ, Yang L, Gunter LE (1992) Demethylation of satellite I DNA during senescence of bovine adrenocortical cells in culture. Mutat Res 275:13–19
Huang J, Gan Q, Han L, Li J, Zhang H, Sun Y, Zhang Z, Tong T (2008) SIRT1 overexpression antagonizes cellular senescence with activated ERK/S6k1 signaling in human diploid fibroblasts. PLoS One 3:e1710
Imai S, Guarente L (2010) Ten years of NAD-dependent SIR2 family deacetylases: implications for metabolic diseases. Trends Pharmacol Sci 31:212–220
Issa JP, Ottaviano YL, Celano P, Hamilton SR, Davidson NE, Baylin SB (1994) Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genet 7:536–540
Jenuwein T, Allis CD (2001) Translating the histone code. Science 293:1074–1080
Johnson BR, Nitta RT, Frock RL, Mounkes L, Barbie DA, Stewart CL, Harlow E, Kennedy BK (2004) A-type lamins regulate retinoblastoma protein function by promoting subnuclear localization and preventing proteasomal degradation. Proc Natl Acad Sci U S A 101:9677–9682
Jung-Hynes B, Nihal M, Zhong W, Ahmad N (2009) Role of sirtuin histone deacetylase SIRT1 in prostate cancer. A target for prostate cancer management via its inhibition? J Biol Chem 284:3823–3832
Jurkowska RZ, Jurkowski TP, Jeltsch A (2011) Structure and function of mammalian DNA methyltransferases. Chembiochem 12:206–222
Kaeberlein M, McVey M, Guarente L (1999) The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev 13:2570–2580
Kawahara TL, Rapicavoli NA, Wu AR, Qu K, Quake SR, Chang HY (2011) Dynamic chromatin localization of Sirt6 shapes stress- and aging-related transcriptional networks. PLoS Genet 7:e1002153
Kawakami K, Nakamura A, Ishigami A, Goto S, Takahashi R (2009) Age-related difference of site-specific histone modifications in rat liver. Biogerontology 10:415–421
Kenyon J, Gerson SL (2007) The role of DNA damage repair in aging of adult stem cells. Nucleic Acids Res 35:7557–7565
Kimura H, Shiota K (2003) Methyl-CpG-binding protein, MeCP2, is a target molecule for maintenance DNA methyltransferase, Dnmt1. J Biol Chem 278:4806–4812
Kirkwood TL, Kapahi P, Shanley DP (2000) Evolution, stress, and longevity. J Anat 197(Pt 4):587–590
Knight JA (2000) The biochemistry of aging. Adv Clin Chem 35:1–62
Koch CM, Suschek CV, Lin Q, Bork S, Goergens M, Joussen S, Pallua N, Ho AD, Zenke M, Wagner W (2011) Specific age-associated DNA methylation changes in human dermal fibroblasts. PLoS One 6:e16679
Kosar M, Bartkova J, Hubackova S, Hodny Z, Lukas J, Bartek J (2011) 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 10:457–468
Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705
Kozak ML, Chavez A, Dang W, Berger SL, Ashok A, Guo X, Johnson FB (2010) Inactivation of the Sas2 histone acetyltransferase delays senescence driven by telomere dysfunction. EMBO J 29:158–170
Krishnan V, Chow MZ, Wang Z, Zhang L, Liu B, Liu X, Zhou Z (2011) Histone H4 lysine 16 hypoacetylation is associated with defective DNA repair and premature senescence in Zmpste24-deficient mice. Proc Natl Acad Sci U S A 108:12325–12330
Langley E, Pearson M, Faretta M, Bauer UM, Frye RA, Minucci S, Pelicci PG, Kouzarides T (2002) Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. EMBO J 21:2383–2396
Lee ST, Kim M (2006) Aging and neurodegeneration. Molecular mechanisms of neuronal loss in Huntington’s disease. Mech Ageing Dev 127:432–435
Lee S, Jung JW, Park SB, Roh K, Lee SY, Kim JH, Kang SK, Kang KS (2011) Histone deacetylase regulates high mobility group A2-targeting microRNAs in human cord blood-derived multipotent stem cell aging. Cell Mol Life Sci 68:325–336
Legube G, Trouche D (2003) Regulating histone acetyltransferases and deacetylases. EMBO Rep 4:944–947
Li G, Reinberg D (2011) Chromatin higher-order structures and gene regulation. Curr Opin Genet Dev 21:175–186
Li N, Bates DJ, An J, Terry DA, Wang E (2011) Up-regulation of key microRNAs, and inverse down-regulation of their predicted oxidative phosphorylation target genes, during aging in mouse brain. Neurobiol Aging 32:944–955
Liang R, Bates DJ, Wang E (2009) Epigenetic control of microRNA expression and aging. Curr Genomics 10:184–193
Lopatina N, Haskell JF, Andrews LG, Poole JC, Saldanha S, Tollefsbol T (2002) Differential maintenance and de novo methylating activity by three DNA methyltransferases in aging and immortalized fibroblasts. J Cell Biochem 84:324–334
Lopatina NG, Poole JC, Saldanha SN, Hansen NJ, Key JS, Pita MA, Andrews LG, Tollefsbol TO (2003) Control mechanisms in the regulation of telomerase reverse transcriptase expression in differentiating human teratocarcinoma cells. Biochem Biophys Res Commun 306:650–659
Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ (1997) Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389:251–260
Maes OC, An J, Sarojini H, Wang E (2008) Murine microRNAs implicated in liver functions and aging process. Mech Ageing Dev 129:534–541
Margueron R, Trojer P, Reinberg D (2005) The key to development: interpreting the histone code? Curr Opin Genet Dev 15:163–176
Michishita E, McCord RA, Berber E, Kioi M, Padilla-Nash H, Damian M, Cheung P, Kusumoto R, Kawahara TL, Barrett JC, Chang HY, Bohr VA, Ried T, Gozani O, Chua KF (2008) SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature 452:492–496
Misteli T (2010) Higher-order genome organization in human disease. Cold Spring Harb Perspect Biol 2:a000794
Morimoto S, Komatsu S, Takahashi R, Matsuo M, Goto S (1993) Age-related change in the amount of ubiquitinated histones in the mouse brain. Arch Gerontol Geriatr 16:217–224
Mostoslavsky R, Chua KF, Lombard DB, Pang WW, Fischer MR, Gellon L, Liu P, Mostoslavsky G, Franco S, Murphy MM, Mills KD, Patel P, Hsu JT, Hong AL, Ford E, Cheng HL, Kennedy C, Nunez N, Bronson R, Frendewey D, Auerbach W, Valenzuela D, Karow M, Hottiger MO, Hursting S, Barrett JC, Guarente L, Mulligan R, Demple B, Yancopoulos GD, Alt FW (2006) Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 124:315–329
Muller M (2009) Cellular senescence: molecular mechanisms, in vivo significance, and redox considerations. Antioxid Redox Signal 11:59–98
Munro J, Barr NI, Ireland H, Morrison V, Parkinson EK (2004) Histone deacetylase inhibitors induce a senescence-like state in human cells by a p16-dependent mechanism that is independent of a mitotic clock. Exp Cell Res 295:525–538
Murr R (2010) Interplay between different epigenetic modifications and mechanisms. Adv Genet 70:101–141
Narita M (2007) Cellular senescence and chromatin organisation. Br J Cancer 96:686–691
Narita M, Nunez S, Heard E, Lin AW, Hearn SA, Spector DL, Hannon GJ, Lowe SW (2003) Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 113:703–716
Narita M, Krizhanovsky V, Nunez S, Chicas A, Hearn SA, Myers MP, Lowe SW (2006) A novel role for high-mobility group a proteins in cellular senescence and heterochromatin formation. Cell 126:503–514
Newman BL, Lundblad JR, Chen Y, Smolik SM (2002) A Drosophila homologue of Sir2 modifies position-effect variegation but does not affect life span. Genetics 162:1675–1685
O’Hagan HM, Mohammad HP, Baylin SB (2008) Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island. PLoS Genet 4:e1000155
O’Sullivan RJ, Kubicek S, Schreiber SL, Karlseder J (2010) Reduced histone biosynthesis and chromatin changes arising from a damage signal at telomeres. Nat Struct Mol Biol 17:1218–1225
Oakes CC, Smiraglia DJ, Plass C, Trasler JM, Robaire B (2003) Aging results in hypermethylation of ribosomal DNA in sperm and liver of male rats. Proc Natl Acad Sci U S A 100:1775–1780
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 135:907–918
Ota H, Tokunaga E, Chang K, Hikasa M, Iijima K, Eto M, Kozaki K, Akishita M, Ouchi Y, Kaneki M (2006) Sirt1 inhibitor, Sirtinol, induces senescence-like growth arrest with attenuated Ras-MAPK signaling in human cancer cells. Oncogene 25:176–185
Ota H, Akishita M, Eto M, Iijima K, Kaneki M, Ouchi Y (2007) Sirt1 modulates premature senescence-like phenotype in human endothelial cells. J Mol Cell Cardiol 43:571–579
Ozaki T, Saijo M, Murakami K, Enomoto H, Taya Y, Sakiyama S (1994) Complex formation between lamin A and the retinoblastoma gene product: identification of the domain on lamin A required for its interaction. Oncogene 9:2649–2653
Palacios JA, Herranz D, De Bonis ML, Velasco S, Serrano M, Blasco MA (2010) SIRT1 contributes to telomere maintenance and augments global homologous recombination. J Cell Biol 191:1299–1313
Paull TT, Haykinson MJ, Johnson RC (1993) The nonspecific DNA-binding and -bending proteins HMG1 and HMG2 promote the assembly of complex nucleoprotein structures. Genes Dev 7:1521–1534
Pedeux R, Sengupta S, Shen JC, Demidov ON, Saito S, Onogi H, Kumamoto K, Wincovitch S, Garfield SH, McMenamin M, Nagashima M, Grossman SR, Appella E, Harris CC (2005) ING2 regulates the onset of replicative senescence by induction of p300-dependent p53 acetylation. Mol Cell Biol 25:6639–6648
Peterson CL, Laniel MA (2004) Histones and histone modifications. Curr Biol 14:R546–R551
Prieur A, Besnard E, Babled A, Lemaitre JM (2011) p53 and p16(INK4A) independent induction of senescence by chromatin-dependent alteration of S-phase progression. Nat Commun 2:473
Rakyan VK, Down TA, Maslau S, Andrew T, Yang TP, Beyan H, Whittaker P, McCann OT, Finer S, Valdes AM, Leslie RD, Deloukas P, Spector TD (2010) Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains. Genome Res 20:434–439
Rastogi S, Joshi B, Dasgupta P, Morris M, Wright K, Chellappan S (2006) Prohibitin facilitates cellular senescence by recruiting specific corepressors to inhibit E2F target genes. Mol Cell Biol 26:4161–4171
Rathbone CR, Booth FW, Lees SJ (2008) FoxO3a preferentially induces p27Kip1 expression while impairing muscle precursor cell-cycle progression. Muscle Nerve 37:84–89
Rodier F, Campisi J (2011) Four faces of cellular senescence. J Cell Biol 192:547–556
Rodriguez RM, Fraga MF (2010) Aging and cancer: are sirtuins the link? Future Oncol 6:905–915
Rogina B, Helfand SL (2004) Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci U S A 101:15998–16003
Romanov GA, Vanyushin BF (1981) Methylation of reiterated sequences in mammalian DNAs. Effects of the tissue type, age, malignancy and hormonal induction. Biochim Biophys Acta 653:204–218
Rusche LN, Kirchmaier AL, Rine J (2003) The establishment, inheritance, and function of silenced chromatin in Saccharomyces cerevisiae. Annu Rev Biochem 72:481–516
Saito Y, Jones PA (2006) Epigenetic activation of tumor suppressor microRNAs in human cancer cells. Cell Cycle 5:2220–2222
Sarg B, Koutzamani E, Helliger W, Rundquist I, Lindner HH (2002) Postsynthetic trimethylation of histone H4 at lysine 20 in mammalian tissues is associated with aging. J Biol Chem 277:39195–39201
Sayed D, Abdellatif M (2011) MicroRNAs in development and disease. Physiol Rev 91:827–887
Sedivy JM, Banumathy G, Adams PD (2008) Aging by epigenetics–a consequence of chromatin damage? Exp Cell Res 314:1909–1917
Seviour EG, Lin SY (2010) The DNA damage response: balancing the scale between cancer and ageing. Aging (Albany NY) 2:900–907
Shin DM, Kucia M, Ratajczak MZ (2011a) Nuclear and chromatin reorganization during cell senescence and aging – a mini-review. Gerontology 57:76–84
Shin KH, Pucar A, Kim RH, Bae SD, Chen W, Kang MK, Park NH (2011b) Identification of senescence-inducing microRNAs in normal human keratinocytes. Int J Oncol 39:1205–1211
Shumaker DK, Dechat T, Kohlmaier A, Adam SA, Bozovsky MR, Erdos MR, Eriksson M, Goldman AE, Khuon S, Collins FS, Jenuwein T, Goldman RD (2006) Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. Proc Natl Acad Sci U S A 103:8703–8708
Sinclair DA, Guarente L (1997) Extrachromosomal rDNA circles–a cause of aging in yeast. Cell 91:1033–1042
Singhal RP, Mays-Hoopes LL, Eichhorn GL (1987) DNA methylation in aging of mice. Mech Ageing Dev 41:199–210
So K, Tamura G, Honda T, Homma N, Waki T, Togawa N, Nishizuka S, Motoyama T (2006) Multiple tumor suppressor genes are increasingly methylated with age in non-neoplastic gastric epithelia. Cancer Sci 97:1155–1158
So AY, Jung JW, Lee S, Kim HS, Kang KS (2011) DNA methyltransferase controls stem cell aging by regulating BMI1 and EZH2 through microRNAs. PLoS One 6:e19503
Song JZ, Stirzaker C, Harrison J, Melki JR, Clark SJ (2002) Hypermethylation trigger of the glutathione-S-transferase gene (GSTP1) in prostate cancer cells. Oncogene 21:1048–1061
Steuerwald NM, Parsons JC, Bennett K, Bates TC, Bonkovsky HL (2010) Parallel microRNA and mRNA expression profiling of (genotype 1b) human hepatoma cells expressing hepatitis C virus. Liver Int 30:1490–1504
Stirzaker C, Song JZ, Davidson B, Clark SJ (2004) Transcriptional gene silencing promotes DNA hypermethylation through a sequential change in chromatin modifications in cancer cells. Cancer Res 64:3871–3877
Swisshelm K, Disteche CM, Thorvaldsen J, Nelson A, Salk D (1990) Age-related increase in methylation of ribosomal genes and inactivation of chromosome-specific rRNA gene clusters in mouse. Mutat Res 237:131–146
Tao D, Lu J, Sun H, Zhao YM, Yuan ZG, Li XX, Huang BQ (2004) Trichostatin A extends the lifespan of Drosophila melanogaster by elevating hsp22 expression. Acta Biochim Biophys Sin (Shanghai) 36:618–622
Thevenet L, Mejean C, Moniot B, Bonneaud N, Galeotti N, Aldrian-Herrada G, Poulat F, Berta P, Benkirane M, Boizet-Bonhoure B (2004) Regulation of human SRY subcellular distribution by its acetylation/deacetylation. EMBO J 23:3336–3345
Trimarchi JM, Lees JA (2002) Sibling rivalry in the E2F family. Nat Rev Mol Cell Biol 3:11–20
Vaquero A, Scher M, Lee D, Erdjument-Bromage H, Tempst P, Reinberg D (2004) Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin. Mol Cell 16:93–105
Vaquero A, Scher M, Erdjument-Bromage H, Tempst P, Serrano L, Reinberg D (2007) SIRT1 regulates the histone methyl-transferase SUV39H1 during heterochromatin formation. Nature 450:440–444
Villa R, Morey L, Raker VA, Buschbeck M, Gutierrez A, De Santis F, Corsaro M, Varas F, Bossi D, Minucci S, Pelicci PG, Di Croce L (2006) The methyl-CpG binding protein MBD1 is required for PML-RARalpha function. Proc Natl Acad Sci U S A 103:1400–1405
Vogt M, Haggblom C, Yeargin J, Christiansen-Weber T, Haas M (1998) Independent induction of senescence by p16INK4a and p21CIP1 in spontaneously immortalized human fibroblasts. Cell Growth Differ 9:139–146
Waki T, Tamura G, Sato M, Motoyama T (2003) Age-related methylation of tumor suppressor and tumor-related genes: an analysis of autopsy samples. Oncogene 22:4128–4133
Walter D, Matter A, Fahrenkrog B (2010) Bre1p-mediated histone H2B ubiquitylation regulates apoptosis in Saccharomyces cerevisiae. J Cell Sci 123:1931–1939
Wilson VL, Jones PA (1983) DNA methylation decreases in aging but not in immortal cells. Science 220:1055–1057
Wilson VL, Smith RA, Ma S, Cutler RG (1987) Genomic 5-methyldeoxycytidine decreases with age. J Biol Chem 262:9948–9951
Xu WS, Perez G, Ngo L, Gui CY, Marks PA (2005) Induction of polyploidy by histone deacetylase inhibitor: a pathway for antitumor effects. Cancer Res 65:7832–7839
Yamakuchi M, Ferlito M, Lowenstein CJ (2008) miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci U S A 105:13421–13426
Yang X, Phillips DL, Ferguson AT, Nelson WG, Herman JG, Davidson NE (2001) Synergistic activation of functional estrogen receptor (ER)-alpha by DNA methyltransferase and histone deacetylase inhibition in human ER-alpha-negative breast cancer cells. Cancer Res 61:7025–7029
Ye X, Zerlanko B, Zhang R, Somaiah N, Lipinski M, Salomoni P, Adams PD (2007) Definition of pRB- and p53-dependent and -independent steps in HIRA/ASF1a-mediated formation of senescence-associated heterochromatin foci. Mol Cell Biol 27:2452–2465
Yoshimi A, Kurokawa M (2011) Key roles of histone methyltransferase and demethylase in leukemogenesis. J Cell Biochem 112:415–424
Yuan F, Xie Q, Wu J, Bai Y, Mao B, Dong Y, Bi W, Ji G, Tao W, Wang Y, Yuan Z (2011) MST1 promotes apoptosis through regulating Sirt1-dependent p53 deacetylation. J Biol Chem 286:6940–6945
Zhang T, Kraus WL (2010) SIRT1-dependent regulation of chromatin and transcription: linking NAD(+) metabolism and signaling to the control of cellular functions. Biochim Biophys Acta 1804:1666–1675
Zhang R, Poustovoitov MV, Ye X, Santos HA, Chen W, Daganzo SM, Erzberger JP, Serebriiskii IG, Canutescu AA, Dunbrack RL, Pehrson JR, Berger JM, Kaufman PD, Adams PD (2005) Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. Dev Cell 8:19–30
Zhang J, Liu Q, Zhang W, Li J, Li Z, Tang Z, Li Y, Han C, Hall SH, Zhang Y (2010) Comparative profiling of genes and miRNAs expressed in the newborn, young adult, and aged human epididymides. Acta Biochim Biophys Sin (Shanghai) 42:145–153
Zhao Y, Sun H, Lu J, Li X, Chen X, Tao D, Huang W, Huang B (2005) Lifespan extension and elevated hsp gene expression in Drosophila caused by histone deacetylase inhibitors. J Exp Biol 208:697–705
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Lazarus, A., Banerjee, K.K., Kolthur-Seetharam, U. (2013). Small Changes, Big Effects: Chromatin Goes Aging. In: Kundu, T. (eds) Epigenetics: Development and Disease. Subcellular Biochemistry, vol 61. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4525-4_8
Download citation
DOI: https://doi.org/10.1007/978-94-007-4525-4_8
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-4524-7
Online ISBN: 978-94-007-4525-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)