Epigenetic changes during aging and their reprogramming potential

References

• Abad M, Mosteiro L, Pantoja C, Cañamero M, Rayon T, Ors I, Graña O, Megías D, Domínguez O, Martínez D, et al. 2013. Reprogramming in vivo produces teratomas and iPS cells with totipotency features. Nature. 502:340–345.
   PubMed Web of Science ®Google Scholar
• Alfego D, Rodeck U, Kriete A. 2018. Global mapping of transcription factor motifs in human aging. PLoS One. 13:e0190457.
   PubMed Web of Science ®Google Scholar
• Alvarez-Garcia O, Matsuzaki T, Olmer M, Masuda K, Lotz MK. 2017. Age-related reduction in the expression of FOXO transcription factors and correlations with intervertebral disc degeneration. J Orthop Res. 35:2682–2691.
   PubMed Web of Science ®Google Scholar
• Anckar J, Sistonen L. 2011. Regulation of HSF1 function in the heat stress response: implications in aging and disease. Annu Rev Biochem. 80:1089–1115.
   PubMed Web of Science ®Google Scholar
• Armour SM, Bennett EJ, Braun CR, Zhang X-Y, McMahon SB, Gygi SP, Harper JW, Sinclair DA. 2013. A high-confidence interaction map identifies SIRT1 as a mediator of acetylation of USP22 and the SAGA coactivator complex. Mol Cell Biol. 33:1487–1502.
   PubMed Web of Science ®Google Scholar
• Austriaco NR, Guarente LP. 1997. Changes of telomere length cause reciprocal changes in the lifespan of mother cells in Saccharomyces cerevisiae. Proc Natl Acad Sci USA. 94:9768–9772.
   PubMed Web of Science ®Google Scholar
• Avrahami D, Li C, Zhang J, Schug J, Avrahami R, Rao S, Stadler MB, Burger L, Schübeler D, Glaser B, Kaestner KH. 2016. Aging-dependent demethylation of regulatory elements correlates with chromatin state and improved β-cell function. Cell Metab. 22:619–632.
   Web of Science ®Google Scholar
• Bannister AJ, Kouzarides T. 2011. Regulation of chromatin by histone modifications. Cell Res. 21:381–395.
   PubMed Web of Science ®Google Scholar
• Baumgart M, Groth M, Priebe S, Testa G, Dix A, Ripa R, Spallotta F, Gaetano C, Ori M, Tozzini T, et al. 2014. RNA-seq of the aging brain in the short-lived fish N. furzeri – conserved pathways and novel genes associated with neurogenesis. Aging Cell. 13:965–974.
   PubMed Web of Science ®Google Scholar
• Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, et al. 2006. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 444:337–342.
   PubMed Web of Science ®Google Scholar
• Beerman I, Bock C, Garrison BS, Smith ZD, Gu H, Meissner A, Rossi DJ. 2013. Proliferation-dependent alterations of the DNA methylation landscape underlie hematopoietic stem cell aging. Cell Stem Cell. 12:413–425.
   PubMed Web of Science ®Google Scholar
• Benayoun B, Pollina EA, Brunet A. 2015. Epigenetic regulation of ageing: linking environmental inputs to genomic stability. Nat Rev Mol Cell Biol. 16:593–610.
   PubMed Web of Science ®Google Scholar
• Berdyshev G, Korotaev G, Boiarskikh G, Vaniushin B. 1967. Nucleotide composition of DNA and RNA from somatic tissues of humpback and its changes during spawning. Biokhimiia. 32:988–993.
   PubMedGoogle Scholar
• Bjornsson H, Sigurdsson MI, Fallin MD, Irizarry RA, Aspelund T, Cui H, Yu W, Rongione MA, Ekström TJ, Harris TB, et al. 2008. Intra-individual change over time in DNA methylation with familial clustering. JAMA. 299:2877–2883.
   PubMed Web of Science ®Google Scholar
• Blackwell TK, Steinbaugh MJ, Hourihan JM, Ewald CY, Isik M. 2016. SKN-1/Nrf, stress responses, and aging in Caenorhabditis elegans. Free Radic Biol Med. 88:290–301.
   Web of Science ®Google Scholar
• Bocker MT, Hellwig I, Breiling A, Eckstein V, Ho AD, Lyko F. 2011. Genome-wide promoter DNA methylation dynamics of human hematopoietic progenitor cells during differentiation and aging. Blood. 117:182–190.
   PubMed Web of Science ®Google Scholar
• Boehm M, Slack F. 2005. A developmental timing microRNA and its target regulate life span in C. elegans. Science. 310:1954–1958.
   PubMed Web of Science ®Google Scholar
• Bollati V, Schwartz J, Wright R, Litonjua A, Tarantini L, Suh H, Sparrow D, Vokonas P, Baccarelli A. 2009. Decline in genomic DNA methylation through aging in a cohort of elderly subjects. Mech Ageing Dev. 130:234–239.
   PubMed Web of Science ®Google Scholar
• Booth L, Brunet A. 2016. The aging epigenome. Mol Cell. 62:728–744.
   PubMed Web of Science ®Google Scholar
• Bormann F, Rodríguez-Paredes M, Hagemann S, Manchanda H, Kristof B, Gutekunst J, Raddatz G, Haas R, Terstegen L, Wenck H, et al. 2016. Reduced DNA methylation patterning and transcriptional connectivity define human skin aging. Aging Cell. 15:563–571.
   PubMed Web of Science ®Google Scholar
• Brack AS, Conboy MJ, Roy S, Lee M, Kuo CJ, Keller C, Rando TA. 2007. Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science. 317:807–811.
   PubMed Web of Science ®Google Scholar
• Brandt A, Krohne G, Grosshans J. 2008. The farnesylated nuclear proteins KUGELKERN and LAMIN B promote aging-like phenotypes in Drosophila flies. Aging Cell. 7:541–551.
   PubMed Web of Science ®Google Scholar
• Brunquell J, Morris S, Lu Y, Cheng F, Westerheide SD. 2016. The genome-wide role of HSF-1 in the regulation of gene expression in Caenorhabditis elegans. BMC Genomics. 17:559.
   PubMed Web of Science ®Google Scholar
• Budovskaya YV, Wu K, Southworth LK, Jiang M, Tedesco P, Johnson TE, Kim SK. 2008. An elt-3/elt-5/elt-6 GATA transcription circuit guides aging in C. elegans. Cell. 134:291–303.
   PubMed Web of Science ®Google Scholar
• Buganim Y, Faddah DA, Jaenisch R. 2013. Mechanisms and models of somatic cell reprogramming. Nat Rev Genet. 14:427–439.
   PubMed Web of Science ®Google Scholar
• Calo E, Wysocka J. 2013. Modification of enhancer chromatin: what, how and why? Mol Cell. 49:825–837.
   PubMed Web of Science ®Google Scholar
• Cecco M, De Criscione SW, Peterson AL, Neretti N, Sedivy JM, Kreiling JA. 2013. Transposable elements become active and mobile in the genomes of aging mammalian somatic tissues. Aging. 5:867–883.
   PubMedGoogle Scholar
• Cech TR, Steitz JA. 2014. The noncoding RNA revolution-trashing old rules to forge new ones. Cell. 157:77–94.
   PubMed Web of Science ®Google Scholar
• Chen H, Fan M, Pfeffer LM, Laribee RN. 2012. The histone H3 lysine 56 acetylation pathway is regulated by target of rapamycin (TOR) signaling and functions directly in ribosomal RNA biogenesis. Nucleic Acids Res. 40:6534–6546.
   PubMed Web of Science ®Google Scholar
• Chen H, Ruiz PD, McKimpson WM, Novikov L, Kitsis RN, Gamble MJ. 2015. MacroH2A1 and ATM play opposing roles in paracrine senescence and the senescence-associated secretory phenotype. Mol Cell. 59:719–731.
   PubMed Web of Science ®Google Scholar
• Chen H, Zheng X, Xiao D, Zheng Y. 2016. Age-associated de-repression of retrotransposons in the Drosophila fat body, its potential cause and consequence. Aging Cell. 15:542–552.
   PubMed Web of Science ®Google Scholar
• Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y. 2012. Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways. Mol Cell Proteomics. 11:1048–1062.
   PubMed Web of Science ®Google Scholar
• Cheung P, Vallania F, Warsinske HC, Donato M, Schaffert S, Chang SE, Dvorak M, Dekker CL, Davis MM, Utz PJ, et al. 2018. Single-cell chromatin modification profiling reveals increased epigenetic variations with aging. Cell. 173:1385–1397.e14.
   PubMed Web of Science ®Google Scholar
• Christensen BC, Houseman EA, Marsit CJ, Zheng S, Wrensch MR, Wiemels JL, Nelson HH, Karagas MR, Padbury JF, Bueno R, et al. 2009. Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CPG island context. PLoS Genet. 5:e1000602.
   PubMed Web of Science ®Google Scholar
• Clapier CR, Cairns BR. 2009. The biology of chromatin remodeling complexes. Annu Rev Biochem. 78:273–304.
   PubMed Web of Science ®Google Scholar
• Clevers H. 2006. Wnt/beta-catenin signaling in development and disease. Cell. 127:469–480.
   PubMed Web of Science ®Google Scholar
• Cole JJ, Robertson NA, Rather MI, Thomson JP, McBryan T, Sproul D, Wang T, Brock C, Clark W, Ideker T, et al. 2017. Diverse interventions that extend mouse lifespan suppress shared age-associated epigenetic changes at critical gene regulatory regions. Genome Biol. 18:1–16.
   PubMed Web of Science ®Google Scholar
• Costa F. 2010. Non-coding RNAs: meet thy masters. Bioessays. 32:599–608.
   PubMed Web of Science ®Google Scholar
• Damelin M, Simon I, Moy TI, Wilson B, Komili S, Tempst P, Roth FP, Young RA, Cairns BR, Silver PA. 2002. The genome-wide localization of Rsc9, a component of the RSC chromatin-remodeling complex, changes in response to stress. Mol Cell. 9:563–573.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Dang W, Sutphin GL, Dorsey JA, Otte GL, Cao K, Perry M, Wanat JJ, Saviolaki D, Murakami CJ, Robison B, et al. 2015. Inactivation of yeast Isw2 chromatin remodeling enzyme mimics longevity effect of calorie restriction via induction of genotoxic stress response. Cell Metab. 19:952–966.
   Web of Science ®Google Scholar
• de Lázaro I, Cossu G, Kostarelos K. 2017. Transient transcription factor (OSKM) expression is key towards clinical translation of in vivo cell reprogramming. EMBO Mol Med. 9:733–736.
   PubMed Web of Science ®Google Scholar
• Deininger P. 2011. Alu elements: Know the SINEs. Genome Biol. 12:236.
   PubMed Web of Science ®Google Scholar
• Dennis S, Sheth U, Feldman JL, English KA, Priess JR. 2012. C. elegans germ cells show temperature and age-dependent expression of Cer1, a Gypsy/Ty3-related retrotransposon. PLoS Pathog. 8:e1002591.
   PubMed Web of Science ®Google Scholar
• Dobbin MM, Madabhushi R, Pan L, Chen Y, Kim D, Gao J, Ahanonu B, Pao PC, Qiu Y, Zhao Y, et al. 2013. SIRT1 collaborates with ATM and HDAC1 to maintain genomic stability in neurons. Nat Neurosci. 16:1008–1015.
   PubMed Web of Science ®Google Scholar
• Duarte LF, Young ARJ, Wang Z, Wu H, Panda T, Kou Y, Kapoor A, Hasson D, Mills NR, Ma A. 2015. Histone H3.3 and its proteolytically processed form drive a cellular senescence program. Nat Commun. 5:5210.
   Web of Science ®Google Scholar
• Eijkelenboom A, Burgering BMT. 2013. FOXOs: signalling integrators for homeostasis maintenance. Nat Rev Mol Cell Biol. 14:83–97.
   PubMed Web of Science ®Google Scholar
• Eisenberg T, Knauer H, Schauer A, Büttner S, Ruckenstuhl C, Carmona D, Ring J, Schroeder S, Magnes C, Antonacci L, et al. 2009. Induction of autophagy by spermidine promotes longevity. Nat Cell Biol. 11:1305–1314.
   PubMed Web of Science ®Google Scholar
• El-Sharnouby S, Fischer B, Magbanua JP, Umans B, Flower R, Choo SW, Russell S, White R. 2017. Regions of very low H3K27me3 partition the Drosophila genome into topological domains. PLoS One. 12:1–23.
   Web of Science ®Google Scholar
• Esteller M. 2011. Non-coding RNAs in human disease. Nat Rev Genet. 12:861–874.
   PubMed Web of Science ®Google Scholar
• Fernández A, Bayón G. 2014. H3K4me1 marks DNA regions hypomethylated during aging in stem and differentiated cells. Genome Res. 27–40.
   PubMed Web of Science ®Google Scholar
• Feser J, Truong D, Das C, Carson JJ, Kieft J, Harkness T, Tyler JK. 2010. Elevated histone expression promotes lifespan extension. Mol Cell. 39:724–735.
   PubMed Web of Science ®Google Scholar
• Field AE, Adams PD. 2017. Targeting chromatin aging - The epigenetic impact of longevity-associated interventions. Exp Gerontol. 94:29–33.
   PubMed Web of Science ®Google Scholar
• Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Cigudosa JC, Urioste M, Benitez J, Boix-chornet M, et al. 2005. Epigenetic differences arise during the lifetime of monozygotic twins. PNAS. 102:10604–10609.
   PubMed Web of Science ®Google Scholar
• Froberg JE, Yang L, Lee JT. 2013. Guided by RNAs: X-inactivation as a model for lncRNA function. J Mol Biol. 425:3698–3706.
   PubMed Web of Science ®Google Scholar
• Fu V, Dobosy J, Desotelle J, Almassi N, Ewald J, Srinivasan R, Berres M, Svaren J, Weindruch R, Jarrard D. 2008. Aging and cancer-related loss of insulin-like growth factor 2 imprinting in the mouse and human prostate. Cancer Res. 68:6797–6802.
   PubMed Web of Science ®Google Scholar
• Gaspar-maia A, Qadeer ZA, Hasson D, Ratnakumar K, Leu NA, Leroy G, Liu S, Costanzi C, Valle-garcia D, Schaniel C, et al. 2013. MacroH2A histone variants act as a barrier upon reprogramming towards pluripotency. Nat Commun. 4:1565.
   PubMed Web of Science ®Google Scholar
• Ghiraldini FG, Crispim ACV, Mello MLS. 2013. Effects of hyperglycemia and aging on nuclear sirtuins and DNA damage of mouse hepatocytes. Mol Biol Cell. 24:2467–2476.
   PubMed Web of Science ®Google Scholar
• Gong H, Qian H, Ertl R, Astle CM, Wang GG, Harrison DE, Xu X. 2015. Histone modifications change with age, dietary restriction and rapamycin treatment in mouse brain. Oncotarget. 6:15882–15890.
   PubMedGoogle Scholar
• Gorbunova V, Boeke JD, Helfand SL, Sedivy JM. 2014. Human genomics. Sleeping dogs of the genome. Science. 346:1187–1188.
   PubMed Web of Science ®Google Scholar
• Grammatikakis I, Panda AC, Abdelmohsen K, Gorospe M. 2014. Long noncoding RNAs (lncRNAs) and the molecular hallmarks of aging. Aging (Albany NY). 6:992–1009.
   PubMedGoogle Scholar
• Greer E, Maures T, Hauswirth A, Green E, Leeman D, Maro GS, Han S, Banko MR, Gozani O, Brunet A. 2010. Members of the histone H3 lysine 4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans. Nature. 466:383–387.
   PubMed Web of Science ®Google Scholar
• Grewal SIS, Moazed D. 2003. Heterochromatin and epigenetic control of gene expression. Science. 301:798–803.
   PubMed Web of Science ®Google Scholar
• Gritsenko DA, Orlova OA, Linkova NS, Khavinson VK. 2017. Transcription factor p53 and skin aging. Adv Gerontol. 7:114–115.
   Google Scholar
• Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai M-C, Hung T, Argani P, Rinn JL, et al. 2010. Long noncoding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 464:1071–1076.
   PubMed Web of Science ®Google Scholar
• Hahn O, Grönke S, Stubbs TM, Ficz G, Hendrich O, Krueger F, Andrews S, Zhang Q, Wakelam MJ, Beyer A, et al. 2017. Dietary restriction protects from age-associated DNA methylation and induces epigenetic reprogramming of lipid metabolism. Genome Biol. 18:1–18.
   PubMed Web of Science ®Google Scholar
• Haigis MC, Sinclair DA. 2010. Mammalian sirtuins: biological insights and disease relevance. Annu Rev Pathol. 5:253–295.
   PubMed Web of Science ®Google Scholar
• Haithcock E, Dayani Y, Neufeld E, Zahand AJ, Feinstein N, Mattout A, Gruenbaum Y, Liu J. 2005. Age-related changes of nuclear architecture in Caenorhabditis elegans. Proc Natl Acad Sci USA. 102:16690–16695.
   PubMed Web of Science ®Google Scholar
• Hamilton B, Dong Y, Shindo M, Liu W, Odell I, Ruvkun G, Lee SS. 2005. A systematic RNAi screen for longevity genes in C. elegans. Genes Dev. 19:1544–1555.
   PubMed Web of Science ®Google Scholar
• Hansen JC. 2002. Conformational dynamics of the chromatin fiber in solution: determinants, mechanisms, and functions. Annu Rev Biophys Biomol Struct. 31:361–392.
   PubMedGoogle Scholar
• Hansson J, Rafiee MR, Reiland S, Polo JM, Gehring J, Okawa S, Huber W, Hochedlinger K, Krijgsveld J. 2012. Highly coordinated proteome dynamics during reprogramming of somatic cells to pluripotency. Cell Rep. 2:1579–1592.
   PubMed Web of Science ®Google Scholar
• Helin K, Dhanak D. 2013. Chromatin proteins and modifications as drug targets. Nature. 502:480–488.
   PubMed Web of Science ®Google Scholar
• Herbig U, Ferreira M, Condel L, Carey D, Sedivy JM. 2006. Cellular senescence in aging primates. Science. 311:1257.
   PubMed Web of Science ®Google Scholar
• Hooten NN, Abdelmohsen K, Gorospe M, Ejiogu N, Zonderman AB, Evans MK. 2010. microRNA expression patterns reveal differential expression of target genes with age. PLoS One. 5:e10724.
   PubMed Web of Science ®Google Scholar
• Horvath S. 2013. DNA methylation age of human tissues and cell types. Genome Biol. 14:R115.
   PubMed Web of Science ®Google Scholar
• Horvath S, Garagnani P, Bacalini MG, Pirazzini C, Salvioli S, Gentilini D, Di Blasio AM, Giuliani C, Tung S, Vinters HV, et al. 2015. Accelerated epigenetic aging in Down syndrome. Aging Cell. 14:491–495.
   PubMed Web of Science ®Google Scholar
• Horvath S, Levine AJ. 2015. HIV-1 infection accelerates age according to the epigenetic clock. J Infect Dis. 212:1563–1573.
   PubMed Web of Science ®Google Scholar
• Horvath S, Oshima J, Martin GM, Lu AT, Quach A, Felton S, Matsuyama M, Lowe D, Kabacik S, Wilson JG, et al. 2018. Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and ex vivo studies. Aging. 10:1758–1775.
   Google Scholar
• Horvath S, Raj K. 2018. DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet. 19:371–384.
   PubMed Web of Science ®Google Scholar
• Horvath S, Stein DJ, Nicole P, Heany SJ, Kobor MS, Lin DT, Myer L, Zar HJ, Evine AJ, Hoare J. 2018. Perinatally acquired HIV infection accelerates epigenetic aging in South African adolescents. Clin Sci. 32:1465–1474.
   Google Scholar
• Howitz KT, Bitterman K, Cohen H, Lamming D, Lavu S, Wood J, Zipkin R, Chung P, Kisielewski A, Zhang L, et al. 2003. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 425:191–196.
   PubMed Web of Science ®Google Scholar
• Hsu A, Murphy CT, Kenyon C. 2003. Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science. 300:5622.
   Web of Science ®Google Scholar
• Hu Z, Chen K, Xia Z, Chavez M, Pal S, Seol JH, Chen CC, Li W, Tyler JK. 2014. Nucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging. Genes Dev. 28:396–408.
   PubMed Web of Science ®Google Scholar
• Ianni A, Hoelper S, Krueger M, Braun T, Bober E. 2017. Sirt7 stabilizes rDNA heterochromatin through recruitment of DNMT1 and Sirt1. Biochem Biophys Res Commun. 492:434–440.
   PubMed Web of Science ®Google Scholar
• Ibáñez-ventoso C, Yang M, Guo S, Robins H, Padgett RW, Driscoll M. 2006. Modulated microRNA expression during adult lifespan in Caenorhabditis elegans. Aging Cell. 5:235–246.
   PubMed Web of Science ®Google Scholar
• Imai S-I, Kitano H. 1998. Heterochromatin islands and their dynamic reorganization: a hypothesis for three distinctive features of cellular aging. Exp Gerontol. 33:555–570.
   PubMed Web of Science ®Google Scholar
• Imai S, Armstrong CM, Kaeberlein M, Guarente L. 2000. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 403:795–800.
   PubMed Web of Science ®Google Scholar
• Ivanov A, Pawlikowski J, Manoharan I, Tuyn J, Van Nelson DM, Rai TS, Shah PP, Hewitt G, Korolchuk VI, Passos JF, et al. 2013. Lysosome-mediated processing of chromatin in senescence. J Cell Biol. 202:129–143.
   PubMed Web of Science ®Google Scholar
• Jiang N, Du G, Tobias E, Wood JG, Whitaker R, Neretti N, Helfand L. 2013. Dietary and genetic effects on age ‐ related loss of gene silencing reveal epigenetic plasticity of chromatin repression during aging. Aging. 5:813–824.
   PubMedGoogle Scholar
• Jin C, Li J, Green CD, Yu X, Tang X, Han D, Xian B, Wang D, Huang X, Cao X, et al. 2011. Histone demethylase UTX-1 regulates C. elegans life span by targeting the insulin/IGF-1 signaling pathway. Cell Metab. 14:161–172.
   PubMed Web of Science ®Google Scholar
• Jintaridth P, Mutirangura A. 2010. Distinctive patterns of age-dependent hypomethylation in interspersed repetitive sequences. Physiol Genomics. 41:194–200.
   PubMed Web of Science ®Google Scholar
• Jung HJ, Suh Y. 2012. MicroRNA in aging: from discovery to biology. Curr Genomics. 13:548–557.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Kamakaka RT, Biggins S. 2005. Histone variants: deviants? Genes Dev. 19:295–310.
   PubMed Web of Science ®Google Scholar
• Kato M, Chen X, Inukai S, Zhao H, Slack FJ. 2011. Age-associated changes in expression of small, noncoding RNAs, including microRNAs, in C. elegans. RNA. 17:1804–1820.
   PubMed Web of Science ®Google Scholar
• Keizer PLJ, De Laberge RM, Campisi J. 2010. p53: Pro-aging or pro-longevity? Aging (Albany NY). 2:377–379.
   PubMedGoogle Scholar
• Kennedy B, Gotta M, Sinclair D, Mills K, McNab D, Murthy M, Pak S, Laroche T, Gasser S, Guarente L. 1997. Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life span in S. cerevisiae. Cell. 89:381–391.
   PubMed Web of Science ®Google Scholar
• Kim CH, Lee EK, Choi YJ, An HJ, Jeong HO, Park D, Kim BC, Yu BP, Bhak J, Chung HY. 2016. Short-term calorie restriction ameliorates genomewide, age-related alterations in DNA methylation. Aging Cell. 15:1074–1081.
   PubMed Web of Science ®Google Scholar
• Koch CM, Joussen S, Schellenberg A, Lin Q, Zenke M, Wagner W. 2012. Monitoring of cellular senescence by DNA-methylation at specific CpG sites. Aging Cell. 11:366–369.
   PubMed Web of Science ®Google Scholar
• Kouzarides T. 2007. Chromatin modifications and their function. Cell. 128:693–705.
   PubMed Web of Science ®Google Scholar
• Kozlowski M, Ladurner AG. 2015. ATM, MacroH2A.1, and SASP: the checks and balances of cellular senescence. Mol Cell. 59:713–715.
   PubMed Web of Science ®Google Scholar
• Kreiling JA, Tamamori-adachi M, Sexton AN, Jeyapalan JC, Munoz-najar U, Peterson AL, Manivannan J, Elizabeth S, Pchelintsev NA, Adams PD, et al. 2012. Age-associated increase in heterochromatic marks in murine and primate tissues. Aging Cell. 10:292–304.
   Web of Science ®Google Scholar
• Krishnan V, Chow MZY, 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 USA. 108:12325–12330.
   PubMed Web of Science ®Google Scholar
• Kucharski R, Maleszka J, Foret S, Maleszka R. 2008. Nutritional control of reproductive status in honeybees via DNA methylation. Science. 319:1827–1831.
   PubMed Web of Science ®Google Scholar
• Kwon J, Han E, Bui CB, Shin W, Lee J, Lee S, Choi YB, Lee AH, Lee KH, Park C, et al. 2012. Assurance of mitochondrial integrity and mammalian longevity by the p62-Keap1-Nrf2-Nqo1 cascade. EMBO Rep. 13:150–156.
   PubMed Web of Science ®Google Scholar
• Labbadia J, Richard I, Labbadia J, Morimoto RI. 2015. Repression of the heat shock response is a programmed event at the onset of reproduction. Mol Cell. 59:639–650.
   PubMed Web of Science ®Google Scholar
• Lake RJ, Boetefuer EL, Won K, Fan H. 2016. The CSB chromatin remodeler and CTCF architectural protein cooperate in response to oxidative stress. Nucleic Acids Res. 44:2125–2135.
   PubMed Web of Science ®Google Scholar
• Lamming DW. 2005. HST2 mediates SIR2-independent life-span extension by calorie restriction. Science. 309:1861–1864.
   PubMed Web of Science ®Google Scholar
• Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, et al. 2001. Initial sequencing and analysis of the human genome. Nature. 409:860–921.
   PubMed Web of Science ®Google Scholar
• Lapasset L, Milhavet O, Prieur A, Besnard E, Babled A, Ait-Hamou N, Leschik J, Pellestor F, Ramirez J-M, De Vos J, et al. 2011. Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state. Genes Dev. 25:2248–2253.
   PubMed Web of Science ®Google Scholar
• Larrieu D, Britton S, Demir M, Rodriguez R, Jackson SP. 2014. Chemical inhibition of NAT10 corrects defects of laminopathic cells. Science. 344:527–532.
   PubMed Web of Science ®Google Scholar
• Larson K, Yan S, Tsurumi A, Liu J, Zhou J, Gaur K, Guo D, Eickbush TH, Li WX. 2012. Heterochromatin formation promotes longevity and represses ribosomal RNA synthesis. PLoS Genet. 8:e1002473.
   PubMed Web of Science ®Google Scholar
• Lauberth SM, Nakayama T, Wu X, Ferris A, Tang Z, Hughes SH, Roeder RG. 2013. H3K4me3 interactions with TAF3 regulate preinitiation complex assembly and selective gene activation. Cell. 152:1021–1036.
   PubMed Web of Science ®Google Scholar
• de Lázaro I, Yilmazer A, Nam Y, Qubisi S, Maizatul F, Degens H, Cossu G, Kostarelos K. 2019. Non-viral, Tumor-free Induction of Transient Cell Reprogramming in Mouse Skeletal Muscle to Enhance Tissue Regeneration. Mol Ther. 1:59–75.
   Google Scholar
• Lee C, Klopp RG, Weindruch R, Prolla TA. 1999. Gene expression profile of aging and its retardation by caloric restriction. Science. 285:1390–1394.
   PubMed Web of Science ®Google Scholar
• Lee J, Kemper JK. 2010. Controlling SIRT1 expression by microRNAs in health and metabolic disease. Aging. 2:27–34.
   Google Scholar
• Lee JT. 2009. Lessons from X-chromosome inactivation: Long ncRNA as guides and tethers to the epigenome. Genes Dev. 23:1831–1842.
   PubMed Web of Science ®Google Scholar
• Lesur I, Campbell JL. 2004. The transcriptome of prematurely aging yeast cells is similar to that of telomerase-deficient cells. Mol Biol Cell. 15:1297–1312.
   PubMed Web of Science ®Google Scholar
• Levine ME, Lu AT, Quach A, Chen BH, Assimes TL, Bandinelli S, Hou L, Baccarelli AA, Stewart JD, Li Y, et al. 2018. An epigenetic biomarker of aging for lifespan and healthspan. Aging. 10:573–591.
   PubMedGoogle Scholar
• Lewis KN, Wason E, Edrey YH, Kristan DM, Nevo E, Buffenstein R. 2015. Regulation of Nrf2 signaling and longevity in naturally long-lived rodents. Proc Natl Acad Sci USA. 112:201417566.
   Web of Science ®Google Scholar
• Li B, Choulet F, Heng Y, Hao W, Paux E, Liu Z, Yue W, Jin W, Feuillet C, Zhang X. 2013. Wheat centromeric retrotransposons: the new ones take a major role in centromeric structure. Plant J. 73:952–965.
   PubMed Web of Science ®Google Scholar
• Li L, Greer C, Eisenman RN, Secombe J. 2010. Essential functions of the histone demethylase lid. PLoS Genet. 6:e1001221.
   PubMed Web of Science ®Google Scholar
• Li S, Christiansen L, Christensen K, Kruse TA, Redmond P, Marioni RE, Deary IJ, Tan Q. 2017. Identification, replication and characterization of epigenetic remodelling in the aging genome: A cross population analysis. Sci Rep. 7:1–8.
   PubMedGoogle Scholar
• Li X, Khanna A, Li N, Wang E. 2011. Circulatory miR34a as an RNAbased, noninvasive biomarker for brain aging. Aging (Albany NY). 3:985–1002.
   PubMedGoogle Scholar
• Li Y, Daniel M, Tollefsbol TO. 2011. Epigenetic regulation of caloric restriction in aging. BMC Med. 9:1–12.
   PubMed Web of Science ®Google Scholar
• Lin M, Tang L, Reddy MN, Shen CJ. 2005. DNA methyltransferase gene dDnmt2 and longevity of Drosophila. J Biol Chem. 280:861–865.
   PubMed Web of Science ®Google Scholar
• Liu B, Wang Z, Zhang L, Ghosh S, Zheng H, Zhou Z. 2013. Depleting the methyltransferase Suv39h1 improves DNA repair and extends lifespan in a Progeria mouse model. Nat Commun. 4:1812–1868.
   PubMed Web of Science ®Google Scholar
• Liu G, Barkho BZ, Ruiz S, Diep D, Qu J, Yang S, Panopoulos AD, Suzuki K, Kurian L, Walsh C, et al. 2011. Recapitulation of premature aging with iPSCs from Hutchinson Gilford Progeria Syndrome. Nature. 472:221–225.
   PubMed Web of Science ®Google Scholar
• Liu L, Cheung T, Charville G, Marie Ceniza Hurgo B, Leavitt T, Shih J, Brunet A, Rando T. 2013. Chromatin modifications as determinants of muscle stem cell quiescence and chronological aging. Cell Rep. 4:189–204.
   PubMed Web of Science ®Google Scholar
• Liu Y, Wang D-L, Chen S, Zhao L, Sun F-L. 2012. Oncogene Ras/phosphatidylinositol 3-kinase signaling targets histone H3 acetylation at lysine 56. J Biol Chem. 287:41469–41480.
   PubMed Web of Science ®Google Scholar
• Logan CY, Nusse R. 2004. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 20:781–810.
   PubMed Web of Science ®Google Scholar
• Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G, López-otín C, Blasco MA, Partridge L, Serrano M. 2013. The hallmarks of aging. Cell. 153:1194–1217.
   PubMed Web of Science ®Google Scholar
• Lu T, Aron L, Zullo J, Pan Y, Kim H, Chen Y, Yang TH, Kim HM, Drake D, Liu XS, et al. 2014. REST and stress resistance in ageing and Alzheimer's disease. Nature. 507:448–454.
   PubMed Web of Science ®Google Scholar
• Luger K, Rechsteiner TJ, Flaus AJ, Waye MMY, Richmond TJ, Zu C. 1997. Characterization of nucleosome core particles containing histone proteins made in bacteria. J Mol Biol. 272:301–311.
   PubMed Web of Science ®Google Scholar
• Lyu G, Guan Y, Zhang C, Zong L, Sun L, Huang X, Huang L, Zhang L, Tian X, Zhou Z, Tao W. 2018. TGF-β signaling alters H4K20me3 status via miR- 29 and contributes to cellular senescence and cardiac aging. Nat Commun. 9:2560.
   PubMed Web of Science ®Google Scholar
• Madabhushi R, Pan L, Tsai LH. 2014. DNA damage and its links to neurodegeneration. Neuron. 83:266–282.
   PubMed Web of Science ®Google Scholar
• Madeo F, Eisenberg T, Pietrocola F, Kroemer G. 2018. Spermidine in health and disease. Science. 359:6374.
   PubMed Web of Science ®Google Scholar
• Maegawa S, Hinkal G, Kim HS, Shen L, Zhang L, Zhang J, Zhang N, Liang S, Donehower LA, Issa JJ. 2010. Widespread and tissue specific age-related DNA methylation changes in mice. Genome Res. 20:332–340.
   PubMed Web of Science ®Google Scholar
• Maegawa S, Lu Y, Tahara T, Lee JT, Madzo J, Liang S, Jelinek J, Colman RJ, Issa JPJ. 2017. Caloric restriction delays age-related methylation drift. Nat Commun. 8:1–11.
   PubMed Web of Science ®Google Scholar
• Maes OC, An J, Sarojini H, Wu H, Wang E. 2008. Changes in microRNA expression patterns in human fibroblasts after low-LET radiation. J Cell Biochem. 105:824–834.
   PubMed Web of Science ®Google Scholar
• Mahmoudi S, Brunet A. 2012. Aging and reprogramming: a two-way street. Curr Opin Cell Biol. 24:744–756.
   PubMed Web of Science ®Google Scholar
• Maierhofer A, Flunkert J, Oshima J, Martin GM, Haaf T, Horvath S. 2017. Accelerated epigenetic aging in Werner syndrome. Aging (Albany NY). 9:1143–1152.
   PubMedGoogle Scholar
• Mansour AA, Gafni O, Weinberger L, Zviran A, Ayyash M, Rais Y, Krupalnik V, Zerbib M, Amann-Zalcenstein D, Maza I, et al. 2012. The H3K27 demethylase Utx regulates somatic and germ cell epigenetic reprogramming. Nature. 488:409–413.
   PubMed Web of Science ®Google Scholar
• Mao Z, Hine C, Tian X, Van Meter M, Au M, Vaidya A, Seluanov A, Gorbunova V. 2011. SIRT6 promotes DNA repair under stress by activating PARP1. Science. 332:1443–1446.
   PubMed Web of Science ®Google Scholar
• Marion RM, Strati K, Li H, Tejera A, Schoeftner S, Ortega S, Serrano M, Blasco MA. 2009. Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells. Cell Stem Cell. 4:141–154.
   PubMed Web of Science ®Google Scholar
• Martin SG, Laroche T, Suka N, Grunstein M, Gasser SM, Boveresses C, Epalinges C. 1999. Relocalization of telomeric ku and SIR proteins in response to DNA strand breaks in yeast. Cell. 97:621–633.
   PubMed Web of Science ®Google Scholar
• Maures TJ, Greer EL, Hauswirth AG, Brunet A. 2011. H3K27 demethylase UTX-1 regulates C. elegans lifespan in a germline-independent, insulin-dependent, manner. Aging Cell. 10:980–990.
   PubMed Web of Science ®Google Scholar
• Maxwell PH, Burhans WC, Curcio MJ. 2011. Retrotransposition is associated with genome instability during chronological aging. PNAS. 108:20376–20381.
   PubMed Web of Science ®Google Scholar
• Maze I, Wenderski W, Noh K, Bagot RC, Purushothaman I, Elsässer SJ, Guo Y, Ionete C, Hurd YL, Tamminga CA, et al. 2015. Critical role of histone turnover in neuronal transcription and plasticity. Neuron. 87:77–94.
   PubMed Web of Science ®Google Scholar
• Mcainsh AD, Scott-drew S, Murray JAH, Jackson SP. 1999. DNA damage triggers disruption of telomeric silencing and Mec1p-dependent relocation of Sir3p. Curr Biol. 9:963–967.
   PubMed Web of Science ®Google Scholar
• Mcclay JL, Aberg KA, Clark SL, Nerella S, Kumar G, Xie LY, Hudson AD, Harada A, Hultman CM, Magnusson PKE, 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. 23:1175–1185.
   PubMed Web of Science ®Google Scholar
• McCormick MA, Delaney JR, Tsuchiya M, Tsuchiyama S, Shemorry A, Sim S, Chou AC-Z, Ahmed U, Carr D, Murakami CJ, et al. 2015. A comprehensive analysis of replicative lifespan in 4698 single-gene deletion strains uncovers conserved mechanisms of aging. Cell Metab. 22:895–906.
   PubMed Web of Science ®Google Scholar
• Mccormick MA, Mason AG, Guyenet SJ, Dang W, Garza RM, Ting MK, Moller RM, Berger SL, Kaeberlein M, Pillus L, et al. 2014. The SAGA histone deubiquitinase module controls yeast replicative lifespan via Sir2 interaction. Cell Rep. 8:477–486.
   PubMed Web of Science ®Google Scholar
• Merkwirth C, Jovaisaite V, Durieux J, Matilainen O, Jordan SD, Quiros PM, Steffen KK, Williams EG, Mouchiroud L, Tronnes SU, et al. 2016. Epigenomic profiling of young and aged HSCs reveals concerted changes during aging that reinforce self-renewal. Cell. 165:1209–1223.
   PubMed Web of Science ®Google Scholar
• Mertens J, Paquola ACM, Ku M, Hatch E, Böhnke L, Ladjevardi S, Mcgrath S, Campbell B, Lee H, JR, Gonçalves JT, et al. 2018. Directly reprogrammed human neurons retain aging- associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects. Cell Stem Cell. 17:705–718.
   Google Scholar
• Mikkelsen TS, Hanna J, Zhang X, Ku M, Wernig M, Schorderet P, Bernstein BE, Jaenisch R, Lander ES, Meissner A. 2008. Dissecting direct reprogramming through integrative genomic analysis. Nature. 454:49–55.
   PubMed Web of Science ®Google Scholar
• Mills KD, Sinclair DA, Guarente L. 1999. MEC1-dependent redistribution of the Sir3 silencing protein from telomeres to DNA double-strand breaks. Cell. 97:609–620.
   PubMed Web of Science ®Google Scholar
• Monnier P, Martinet C, Pontis J, Stancheva I, Ait-si-ali S, Dandolo L. 2013. H19 lncRNA controls gene expression of the Imprinted Gene Network by recruiting MBD1. Proc Natl Acad Sci USA. 110:20693–20698.
   PubMed Web of Science ®Google Scholar
• Mori MA, Raghavan P, Thomou T, Boucher J, Robida-Stubbs S, Macotela Y, Russell SJ, Kirkland JL, Blackwell KT, Kahn CR, et al. 2012. Role of microRNA processing in adipose tissue in stress defense and longevity. Cell Metab. 16:336–347.
   PubMed Web of Science ®Google Scholar
• Mostoslavsky R, Chua KF, Lombard DB, Pang WW, Fischer MR, Gellon L, Liu P, Mostoslavsky G, Franco S, Murphy MM, et al. 2006. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell. 124:315–329.
   PubMed Web of Science ®Google Scholar
• Narita M, Narita M, Krizhanovsky V, Nuñez 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.
   PubMed Web of Science ®Google Scholar
• Narita M, Nũnez S, Heard E, Narita M, 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.
   PubMed Web of Science ®Google Scholar
• Nashun B, Hill PW, Hajkova P. 2015. Reprogramming of cell fate: epigenetic memory and the erasure of memories past. Embo J. 34:1296–1308.
   PubMed Web of Science ®Google Scholar
• Nativio R, Donahue G, Berson A, Lan Y, Amlie-Wolf A, Tuzer F, Toledo JB, Gosai SJ, Gregory BD, Torres C, et al. 2018. Dysregulation of the epigenetic landscape of normal aging in Alzheimer’s disease. Nat Neurosci. 21:497–505.
   PubMed Web of Science ®Google Scholar
• Nelson DM, Jaber-hijazi F, Cole JJ, Robertson NA, Pawlikowski JS, Norris KT, Criscione SW, Pchelintsev NA, Piscitello D, Stong N, et al. 2016. Mapping H4K20me3 onto the chromatin landscape of senescent cells indicates a function in control of cell senescence and tumor suppression through preservation of genetic and epigenetic stability. Genome Biol. 17:158.
   PubMed Web of Science ®Google Scholar
• Ni Z, Ebata A, Alipanahiramandi E, Lee SS. 2012. Two SET domain containing genes link epigenetic changes and aging in Caenorhabditis elegans. Aging Cell. 11:315–325.
   PubMed Web of Science ®Google Scholar
• Nikolaev LG, Akopov SB, Didych DA, Sverdlov ED. 2009. Vertebrate protein CTCF and its multiple roles in a large-scale regulation of genome activity. CG Genomics. 10:294–302.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Oberdoerffer P, Michan S, Mcvay M, Mostoslavsky R, Park S, Hartlerode A, Stegmuller J, Hafner A, Wright SM, Mills KD, et al. 2008. SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging. Cell. 135:907–918.
   PubMed Web of Science ®Google Scholar
• Oberdoerffer P, Sinclair DA. 2007. The role of nuclear architecture in genomic instability and ageing. Nat Rev Mol Cell Biol. 8:692–702.
   PubMed Web of Science ®Google Scholar
• Ocampo A, Reddy P, Belmonte JCI. 2016. Anti-aging strategies based on cellular reprogramming. Trends Mol Med. 22:725–738.
   PubMed Web of Science ®Google Scholar
• Ocampo A, Reddy P, Martinez-Redondo P, Platero-Luengo A, Hatanaka F, Hishida T, Li M, Lam D, Kurita M, Beyret E, et al. 2016. In vivo amelioration of age-associated hallmarks by partial reprogramming. Cell. 167:1719–1733.e12.
   PubMed Web of Science ®Google Scholar
• Ohnishi K, Semi K, Yamamoto T, Shimizu M, Tanaka A, Mitsunaga K, Okita K, Osafune K, Arioka Y, Maeda T, et al. 2014. Premature termination of reprogramming in vivo leads to cancer development through altered epigenetic regulation. Cell. 156:663–677.
   PubMed Web of Science ®Google Scholar
• Pal S, Tyler J. 2016. Epigenetics and aging. Sci Adv. 2:e1600584.
   PubMed Web of Science ®Google Scholar
• Paredes S, Angulo-ibanez M, Tasselli L, Carlson SM, Zheng W, Li T, Chua KF. 2018. The epigenetic regulator SIRT7 guards against mammalian cellular senescence induced by ribosomal DNA instability. J Biol Chem. 293:11242–11250.
   PubMed Web of Science ®Google Scholar
• Pasque V, Gillich A, Garrett N, Gurdon JB. 2011. Histone variant macroH2A confers resistance to nuclear reprogramming. EMBO J. 30:2373–2387.
   PubMed Web of Science ®Google Scholar
• Pegoraro G, Kubben N, Wickert U, Göhler H, Hoffmann K, Misteli T. 2009. Ageing-related chromatin defects through loss of the NURD complex. Nat Cell Biol. 11:1261–1267.
   PubMed Web of Science ®Google Scholar
• Peleg S, Sananbenesi F, Zovoilis A, Burkhardt S, Bahari-javan S, Agis-balboa RC, Cota P, Wittnam JL, Gogol-doering A, Opitz L, et al. 2010. Associated with age-dependent memory impairment in mice. Science. 328:3–8.
   Web of Science ®Google Scholar
• Petkovich DA, Podolskiy DI, Lobanov AV, Lee SG, Miller RA, Gladyshev VN. 2017. Using DNA methylation profiling to evaluate biological age and longevity interventions. Cell Metab. 25:954–960.e6.
   PubMed Web of Science ®Google Scholar
• Polo JM, Anderssen E, Walsh RM, Schwarz BA, Nefzger CM, Lim SM, Borkent M, Apostolou E, Alaei S, Cloutier J, et al. 2012. A molecular roadmap of reprogramming somatic cells into iPS cells. Cell. 151:1617–1632.
   PubMed Web of Science ®Google Scholar
• Pruitt K, Zinn RL, Ohm JE, Mcgarvey KM, Kang SL, Watkins DN, Herman JG, Baylin SB. 2006. Inhibition of SIRT1 reactivates silenced cancer genes without loss of promoter DNA hypermethylation. PLoS Genet. 2:e40.
   PubMed Web of Science ®Google Scholar
• Pu M, Ni Z, Wang M, Wang X, Wood JG, Helfand SL, Yu H, Lee SS. 2015. Trimethylation of Lys36 on H3 restricts gene expression change during aging and impacts life span. Genes Dev. 29:718–731.
   PubMed Web of Science ®Google Scholar
• Quach A, Levine ME, Tanaka T, Lu AT, Chen BH, Ferrucci L, Ritz B, Bandinelli S, Neuhouser ML, Beasley JM, et al. 2017. Epigenetic clock analysis of diet, exercise, education, and lifestyle factors. Aging (Albany NY). 9:419–446.
   PubMedGoogle Scholar
• Raddatz G, Hagemann S, Aran D, Söhle J, Kulkarni PP, Kaderali L, Hellman A, Winnefeld M, Lyko F. 2013. Aging is associated with highly defined epigenetic changes in the human epidermis. Epigenetics Chromatin. 6.
   PubMed Web of Science ®Google Scholar
• Rakyan VK, Down TA, Maslau S, Andrew T, Yang T, Beyan H, Whittaker P, Mccann OT, Finer S, Valdes AM, et al. 2010. Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains. Genome Res. 20:434–439.
   PubMed Web of Science ®Google Scholar
• Rando TA, Chang HY. 2012. Aging, rejuvenation, and epigenetic reprogramming: resetting the aging clock. Cell. 148:46–57.
   PubMed Web of Science ®Google Scholar
• Ren R, Deng L, Xue Y, Suzuki K, Zhang W, Yu Y, Wu J, Sun L, Gong X, Luan H, et al. 2017. Visualization of aging-associated chromatin alterations with an engineered TALE system. Cell Res. 27:483–504.
   PubMed Web of Science ®Google Scholar
• Riedel CG, Dowen RH, Lourenco GF, Kirienko NV, Heimbucher T, West JA, Bowman SK, Kingston RE, Dillin A, Asara JM, et al. 2013. DAF-16 employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity. Nat Cell Biol. 15:491–501.
   PubMed Web of Science ®Google Scholar
• Rohde JR, Cardenas ME. 2003. The tor pathway regulates gene expression by linking nutrient sensing to histone acetylation. Society. 23:629–635.
   Google Scholar
• Romanov G, Vanyushin B. 1981. Methylation of reiterated sequences in mammalian DNAs. Effects of the tissue type, age, malignancy and hormonal induction. Biochim Biophys Acta. 653:204–218.
   PubMed Web of Science ®Google Scholar
• Ryu SH, Kang K, Yoo T, Joe CO, Chung JH. 2011. Transcriptional repression of repeat-derived transcripts correlates with histone hypoacetylation at repetitive DNA elements in aged mice brain. Exp Gerontol. 46:811–818.
   PubMed Web of Science ®Google Scholar
• Sado T, Brockdorff N. 2013. Advances in understanding chromosome silencing by the long non-coding RNA Xist. Philos Trans R Soc B Biol Sci. 368:160.
   PubMedGoogle Scholar
• Saka K, Ide S, Ganley ARD, Kobayashi T. 2013. Cellular senescence in yeast is regulated by rDNA noncoding transcription. Curr Biol. 23:1794–1798.
   PubMed Web of Science ®Google Scholar
• Salih D, Brunet A. 2008. FoxO transcription factors in the maintenance of cellular homeostasis during aging. Curr Opin Cell Biol. 20:126–136.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Sarkar S, Jun S, Rellick S, Quintana D, Cavendish J, Simpkins J. 2016. Expression of microRNA-34a in Alzheimer's disease brain targets genes linked to synaptic plasticity, energy metabolism, and resting state network activity. Brain Res. 1646:139–151.
   PubMed Web of Science ®Google Scholar
• Scaffidi P, Misteli T. 2006. Lamin A-dependent nuclear defects in human aging. Science. 312:1059–1063.
   PubMed Web of Science ®Google Scholar
• Schaefer M, Pollex T, Hanna K, Tuorto F, Meusburger M, Helm M, Lyko F. 2010. RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage. Genes Dev. 24:1590–1595.
   PubMed Web of Science ®Google Scholar
• Schwoerer S, Becker F, Feller C, Baig A, Koeber U, Henze H, Kraus J, Xin B, Lechel A, Lipka D, et al. 2016. Epigenetic stress responses induce muscle stem cell aging by Hoxa9 developmental signals. Nature. 540:428–432.
   PubMed Web of Science ®Google Scholar
• Sedivy J, Banumathy G, Adams P. 2008. Aging by epigenetics-a consequence of chromatin damage? Exp Cell Res. 314:1909–1917.
   PubMed Web of Science ®Google Scholar
• Sen P, Dang W, Donahue G, Dai J, Dorsey J, Cao X, Liu W, Cao K, Perry R, Lee JY, et al. 2015. H3K36 methylation promotes longevity by enhancing transcriptional fidelity. Genes Dev. 29:1362–1376.
   PubMed Web of Science ®Google Scholar
• Sen P, Shah PP, Nativio R, Berger SL. 2016. Epigenetic mechanisms of longevity and aging. Cell. 166:822–839.
   PubMed Web of Science ®Google Scholar
• Shah K, McCormack CE, Bradbury NA. 2014. Do you know the sex of your cells? Am J Physiol Cell Physiol. 306:C3–C18.
   PubMed Web of Science ®Google Scholar
• Shah PP, Donahue G, Otte GL, Capell BC, Nelson DM, Cao K, Aggarwala V, Cruickshanks HA, Rai TS, McBryan T, et al. 2013. Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape. Genes Dev. 27:1787–1799.
   PubMed Web of Science ®Google Scholar
• Shevchenko AI, Grigor’eva EV, Medvedev SP, Zakharova IS, Dementyeva EV, Elisaphenko EA, Malakhova AA, Pavlova SV, Zakian SM. 2018. Impact of Xist RNA on chromatin modifications and transcriptional silencing maintenance at different stages of imprinted X chromosome inactivation in vole Microtus levis. Chromosoma. 127:129–139.
   PubMed Web of Science ®Google Scholar
• Shumaker DK, Dechat T, Kohlmaier A, Adam SA, Bozovsky MR, Erdos MR, Eriksson M, Goldman AE, Khuon S, Collins FS, et al. 2006. Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. PNAS. 103:8703–8708.
   PubMed Web of Science ®Google Scholar
• Siebold AP, Banerjee R, Tie F, Kiss DL, Moskowitz J, Harte PJ. 2010. Polycomb repressive complex 2 and trithorax modulate Drosophila longevity and stress resistance. PNAS. 107:169–174.
   PubMed Web of Science ®Google Scholar
• Sinclair D, Mills K, Guarente L. 1998. Aging in Saccharomyces cerevisiae. Annu Rev Microbiol. 52:533–560.
   PubMed Web of Science ®Google Scholar
• Sinclair DA, Guarente L. 1997. Extrachromosomal rDNA circles-a cause of aging in yeast. Cell. 91:1033–1042.
   PubMed Web of Science ®Google Scholar
• Sinclair DA, Mills K, Guarente L. 1997. Accelerated aging and nucleolar fragmentation in yeast SGS1 mutants. Science. 277:1313–1316.
   PubMed Web of Science ®Google Scholar
• Sinclair DA, Mills K, Guarente L. 1998. Molecular mechanisms of yeast aging. Trends Biochem Sci. 23:131–134.
   PubMed Web of Science ®Google Scholar
• Sinclair DA, Oberdoerffer P. 2009. The ageing epigenome: damaged beyond repair? Ageing Res Rev. 8:189–198.
   PubMed Web of Science ®Google Scholar
• Singh GM, Danaei G, Farzadfar F, Stevens GA, Woodward M, Wormser D, Kaptoge S, Whitlock G, Qiao Q, Lewington S, et al. 2013. The age-specific quantitative effects of metabolic risk factors on cardiovascular diseases and diabetes: a pooled analysis. PLoS One. 8:e65174.
   PubMed Web of Science ®Google Scholar
• Singh P, Thakur MK. 2018. Histone deacetylase 2 inhibition attenuates downregulation of hippocampal plasticity gene expression during aging. Mol Neurobiol. 55:2432–2442.
   PubMed Web of Science ®Google Scholar
• Skene PJ, Henikoff S. 2013. Histone variants in pluripotency and disease. Development. 140:2513–2524.
   PubMed Web of Science ®Google Scholar
• Slotkin RK, Martienssen R. 2007. Transposable elements and the epigenetic regulation of the genome. Nat Rev Genet. 8:272–285.
   PubMed Web of Science ®Google Scholar
• Sridharan R, Gonzales-Cope M, Chronis C, Bonora G, McKee R, Huang C, Patel S, Lopez D, Mishra N, Pellegrini M, et al. 2013. Proteomic and genomic approaches reveal critical functions of H3K9 methylation and heterochromatin protein-1γ in reprogramming to pluripotency. Nat Cell Biol. 15:872–882.
   PubMed Web of Science ®Google Scholar
• Stubbs TM, Bonder MJ, Stark AK, Krueger F, von Meyenn F, Stegle O, Reik W, Bolland D, Butcher G, Chandra T, et al. 2017. Multi-tissue DNA methylation age predictor in mouse. Genome Biol. 18:1–14.
   PubMed Web of Science ®Google Scholar
• Sun D, Luo M, Jeong M, Rodriguez B, Xia Z, Hannah R, Wang H, Le T, Faull K, Chen R, et al. 2014. Epigenomic profiling of young and aged HSCs reveals concerted changes during aging that reinforce self-renewal. Cell Stem Cell. 14:673–688.
   PubMed Web of Science ®Google Scholar
• Sykiotis G, Bohmann D. 2008. Keap1/Nrf2 signaling regulates oxidative stress tolerance and lifespan in Drosophila. Dev Cell. 14:76–85.
   PubMed Web of Science ®Google Scholar
• Szafranski K, Abraham K, Mekhail K. 2015. Non-coding RNA in neural function, disease, and aging. Front Genet. 6:87.
   PubMed Web of Science ®Google Scholar
• Takahashi K, Yamanaka S. 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 126:663–676.
   PubMed Web of Science ®Google Scholar
• Tan L, Ke Z, Tombline G, Macoretta N, Hayes K, Tian X, Lv R, Ablaeva J, Gilbert M, Bhanu NV, et al. 2017. Naked mole rat cells have a stable epigenome that resists iPSC reprogramming. Stem Cell Rep. 9:1721–1734.
   PubMed Web of Science ®Google Scholar
• Tan M, Luo H, Lee S, Jin F, Yang JS, Montellier E, Buchou T, Cheng Z, Rousseaux S, Rajagopal N, et al. 2011. Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell. 146:1016–1028.
   PubMed Web of Science ®Google Scholar
• Tebey L, Robertson H, Durant S, Vitale S, Penning T, Dinkova-Kostova A, Hayes J. 2016. Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease. Free Radic Biol Med. 88:108–146.
   Web of Science ®Google Scholar
• Teschendorff AE, Menon U, Gentry-maharaj A, Ramus SJ, Weisenberger DJ, Shen H, Campan M, Noushmehr H, Bell CG, Maxwell AP, et al. 2010. Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer. Genome Res. 20:440–446.
   PubMed Web of Science ®Google Scholar
• Thompson MJ, von Holdt B, Horvath S, Pellegrini M. 2017. An epigenetic aging clock for dogs and wolves. Aging (Albany NY). 9:1055–1068.
   PubMedGoogle Scholar
• Tsuchiya M, Dang N, Kerr EO, Hu D, Steffen KK, Oakes JA, Kennedy BK, Kaeberlein M. 2006. Sirtuin-independent effects of nicotinamide on lifespan extension from calorie restriction in yeast. Aging Cell. 5:505–514.
   PubMed Web of Science ®Google Scholar
• Tsurumi A, Li WX. 2012. Global heterochromatin loss: a unifying theory of aging? Epigenetics. 7:680–688.
   PubMed Web of Science ®Google Scholar
• Tullet JMA, Green JW, Au C, Benedetto A, Thompson MA, Clark E, Gilliat AF, Young A, Schmeisser K, Gems D. 2017. The SKN-1/Nrf2 transcription factor can protect against oxidative stress and increase lifespan in C. elegans by distinct mechanisms. Aging Cell. 16:1191–1194.
   PubMed Web of Science ®Google Scholar
• Ungvari Z, Tucsek Z, Sosnowska D, Toth P, Gautam T, Podlutsky A, Csiszar A, Losonczy G, Valcarcel-ares MN, Sonntag WE, Csiszar A. 2013. Aging-induced dysregulation of dicer1-dependent microRNA expression impairs angiogenic capacity of rat cerebromicrovascular endothelial cells. J Gerontol - Ser A Biol Sci Med Sci. 68:877–891.
   PubMed Web of Science ®Google Scholar
• van Meter M, Kashyap M, SR, Geneva A, Morello T, Seluanov A, Gorbunova V. 2014. SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age. Nat Commun. 5:5011.
   PubMed Web of Science ®Google Scholar
• Vanyushin B, Nemirovsky L, Klimenko V, Vasiliev V, Belozersky A. 1973. The 5-methylcytosine in DNA of rats. Tissue and age specificity and the changes induced by hydrocortisone and other agents. Gerontologia. 19:138–152.
   PubMedGoogle Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Vaux D, Pfefferli C, Passannante M, Belhaj K, Essen A, Von Sprecher SG, Mu F, Wicky C. 2013. The Caenorhabditis elegans LET-418/Mi2 plays a conserved role in lifespan regulation. Aging Cell. 12:1012–1020.
   PubMed Web of Science ®Google Scholar
• Venkatraman A, He X, Thorvaldsen J, Sugimura R, Perry J, Tao F, Zhao M, Christenson M, Sanchez R, Yu J, et al. 2013. Maternal imprinting at the H19-Igf2 locus maintains adult haematopoietic stem cell quiescence . Nature. 500:345–349.
   PubMed Web of Science ®Google Scholar
• Villeponteau B. 1997. The heterochromatin loss model of aging. Exp Gerontol. 32:383–394.
   PubMed Web of Science ®Google Scholar
• Wagner W. 2017. Epigenetic aging clocks in mice and men. Genome Biol. 18:17–19.
   PubMed Web of Science ®Google Scholar
• Wahlestedt M, Norddahl GL, Sten G, Ugale A, Frisk MM, Mattsson R, Deierborg T, Sigvardsson M, Bryder D. 2013. An epigenetic component of hematopoietic stem cell aging amenable to reprogramming into a young state. Blood. 121:4257–4265.
   PubMed Web of Science ®Google Scholar
• Wallrath LL. 1998. Unfolding the mysteries of heterochromatin. Curr Opin Genet Dev. 8:147–153.
   PubMed Web of Science ®Google Scholar
• Wang CM, Tsai SN, Yew TW, Kwan YW, Ngai SM. 2010. Identification of histone methylation multiplicities patterns in the brain of senescence-accelerated prone mouse 8. Biogerontology. 11:87–102.
   PubMed Web of Science ®Google Scholar
• Wang J, Geesman GJ, Hostikka SL, Atallah M, Blackwell B, Lee E, Cook PJ, Pasaniuc B, Shariat G, Halperin E, et al. 2011. Inhibition of activated pericentromeric SINE/Alu repeat transcription in senescent human adult stem cells reinstates self-renewal. Cell Cycle. 10:3016–3030.
   PubMed Web of Science ®Google Scholar
• Wang T, Tsui B, Kreisberg JF, Robertson NA, Gross AM, Yu MK, Carter H, Brown-borg HM, Adams PD, Ideker T. 2017. Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment. Genome Biol. 18:1–11.
   PubMed Web of Science ®Google Scholar
• Wang W, Huang Q, Hu Y, Stromberg AJ, Nelson PT. 2011. Patterns of microRNA expression in normal and early Alzheimer’s disease human temporal cortex: white matter versus gray matter. Acta Neuropathol. 121:193–205.
   PubMed Web of Science ®Google Scholar
• Wang WY, Pan L, Su SC, Quinn EJ, Sasaki M, Jimenez JC, MacKenzie IRA, Huang EJ, Tsai LH. 2013. Interaction of FUS and HDAC1 regulates DNA damage response and repair in neurons. Nat Neurosci. 16:1383–1391.
   PubMed Web of Science ®Google Scholar
• Wang X, Liu P, Zhu H, Xu Y, Ma C, Dai X, Huang L, Liu Y, Zhang L, Qin C. 2009. miR-34a, a microRNA up-regulated in a double transgenic mouse model of Alzheimer ’ s disease, inhibits bcl2 translation. Brain Res Bull. 80:268–273.
   PubMed Web of Science ®Google Scholar
• Webb AE, Kundaje A, Brunet A. 2016. Characterization of the direct targets of FOXO transcription factors throughout evolution. Aging Cell. 15:673–685.
   PubMed Web of Science ®Google Scholar
• Wei L, Liu B, Tuo J, Shen D, Chen P, Li Z, Ni J, Dagur P, Sen HN, Jawad S, et al. 2012. Hypomethylation of the IL17RC promoter associates with age-related macular degeneration. Cell Rep. 2:1151–1158.
   PubMed Web of Science ®Google Scholar
• Welstead GG, Creyghton MP, Bilodeau S, Cheng AW, Markoulaki S, Young RA, Jaenisch R. 2012. X-linked H3K27me3 demethylase Utx is required for embryonic development in a sex-specific manner. Proc Natl Acad Sci USA. 109:13004–13009.
   PubMed Web of Science ®Google Scholar
• Williams SK, Truong D, Tyler JK. 2008. Acetylation in the globular core of histone H3 on lysine-56 promotes chromatin disassembly during transcriptional activation. PNAS. 105:9000–9005.
   PubMed Web of Science ®Google Scholar
• Wilson VL, Smith RA, Ma S, Cutler RG. 1987. Genomic 5-methyldeoxycytidine decreases with age. J Biol Chem. 262:9948–9951.
   PubMed Web of Science ®Google Scholar
• Wilusz JE, Sunwoo H, Spector DL. 2009. Long noncoding RNAs: functional surprises from the RNA world. Genes Dev. 23:1494–1504.
   PubMed Web of Science ®Google Scholar
• Wood JG, Helfand SL. 2013. Chromatin structure and transposable elements in organismal aging. Front Endocrinol (Lausanne). 4:274.
   Google Scholar
• Wood JG, Hillenmeyer S, Lawrence C, Chang C, Hosier S, Lightfoot W, Mukherjee E, Jiang N, Schorl C, Brodsky AS, et al. 2010. Chromatin remodeling in the aging genome of Drosophila. Aging Cell. 9:971–978.
   PubMed Web of Science ®Google Scholar
• Wood SH, Dam SV, Craig T, Tacutu R, Toole AO, Merry BJ. 2015. Transcriptome analysis in calorie-restricted rats implicates epigenetic and post- translational mechanisms in neuroprotection and aging. Genome Biol. 16:1–18.
   PubMed Web of Science ®Google Scholar
• Yagi T, Kosakai A, Ito D, Okada Y, Akamatsu W, Nihei Y, Nabetani A, Ishikawa F, Arai Y, Hirose N, et al. 2012. Establishment of induced pluripotent stem cells from centenarians for neurodegenerative disease research. PLoS One. 7:1–7.
   Web of Science ®Google Scholar
• Yan H, Bonasio R, Simola DF, Liebig J, Berger SL, Reinberg D. 2015. DNA methylation in social insects: how epigenetics can control behavior and longevity. Annu Rev Entomol. 60:435–452.
   PubMed Web of Science ®Google Scholar
• Yilmazer A, de Lázaro I, Bussy C, Kostarelos K. 2013. In vivo cell reprogramming towards pluripotency by virus-free overexpression of defined factors. PLoS One. 8:e54754.
   PubMed Web of Science ®Google Scholar
• Yuan T, Jiao Y, Jong SD, Ophoff RA, Beck S. 2015. An integrative multi-scale analysis of the dynamic DNA methylation landscape in aging. PLoS Genet. 11:e10014996.
   Web of Science ®Google Scholar
• Zahn JM, Poosala S, Owen AB, Ingram DK, Lustig A, Carter A, Weeraratna AT, Taub DD, Gorospe M, Mazan-mamczarz K, et al. 2007. AGEMAP: a gene expression database for aging in mice. PLoS Genet. 3:e201.
   PubMed Web of Science ®Google Scholar
• Zampieri M, Ciccarone F, Calabrese R, Franceschi C, Bürkle A, Caiafa P. 2015. Reconfiguration of DNA methylation in aging. Mech Ageing Dev. 151:60–70.
   PubMed Web of Science ®Google Scholar
• Zaret KS, Carroll JS. 2011. Pioneer transcription factors: establishing competence for gene expression. Genes Dev. 25:2227–2241.
   PubMed Web of Science ®Google Scholar
• Zentner GE, Tesar PJ, Scacheri PC. 2011. Epigenetic signatures distinguish multiple classes of enhancers with distinct cellular functions. Genome Res. 21:1273–1283.
   PubMed Web of Science ®Google Scholar
• Zhang R, Chen W, Adams PD. 2007. Molecular dissection of formation of senescence-associated heterochromatin foci. Mol Cell Biol. 27:2343–2358.
   PubMed Web of Science ®Google Scholar
• Zhang R, Poustovoitov MV, Ye X, Santos HA, Chen W, Daganzo SM, Erzberger JP, Serebriiskii IG, Canutescu AA, Dunbrack RL, et al. 2005. Formation of macroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. Dev Cell. 8:19–30.
   PubMed Web of Science ®Google Scholar
• Zhang W, Li J, Suzuki K, Qu J, Wang P, Zhou J, Liu X, Ren R, Xu X, Ocampo A, et al. 2015. A Werner syndrome stem cell model\nunveils heterochromatin alterations\nas a driver of human aging. Science. 348:1160–1163.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Fan M, Zhang XUE, Huang F, Wu K, Zhang J, Liu JUN, Huang Z, Luo H, Tao L, Zhang HUI. 2014. Cellular microRNAs up-regulate transcription via interaction with promoter TATA-box motifs. RNA. 20:1878–1889.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Smith CL, Saha A, Grill SW, Mihardja S, Smith SB, Cairns BR, Peterson CL, Bustamante C. 2006. DNA translocation and loop formation mechanism of chromatin remodeling by SWI/SNF and RSC. Mol Cell. 24:559–568.
   PubMed Web of Science ®Google Scholar
• Zhang Z, Deng C, Lu Q, Richardson B. 2002. Age-dependent DNA methylation changes in the ITGAL (CD11a) promoter. Mech Ageing Dev. 123:1257–1268.
   PubMed Web of Science ®Google Scholar
• Zhao Y, Wu D, Fei C, Guo J, Gu S, Zhu Y, Xu F, Zhang Z, Wu L, Li X, Chang C. 2015. Down-regulation of Dicer1 promotes cellular senescence and decreases the differentiation and stem cell-supporting capacities of mesenchymal stromal cells in patients with myelodysplastic syndrome. Haematologica. 100:194–204.
   PubMed Web of Science ®Google Scholar
• Zupkovitz G, Lagger S, Martin D, Steiner M, Hagelkruys A, Seiser C, Schöfer C, Pusch O. 2018. Histone deacetylase 1 expression is inversely correlated with age in the short-lived fish Nothobranchius furzeri. Histochem Cell Biol. 150:225–269.
   Web of Science ®Google Scholar