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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Individual DNA Methylation Profile is Correlated with Age and can be Targeted to Modulate Healthy Aging and Longevity

Author(s): Francesco Guarasci, Patrizia D'Aquila, Alberto Montesanto, Andrea Corsonello, Dina Bellizzi* and Giuseppe Passarino*

Volume 25 , Issue 39 , 2019

Page: [4139 - 4149] Pages: 11

DOI: 10.2174/1381612825666191112095655

Price: $65


Patterns of DNA methylation, the best characterized epigenetic modification, are modulated by aging. In humans, different studies at both site-specific and genome-wide levels have reported that modifications of DNA methylation are associated with the chronological aging process but also with the quality of aging (or biological aging), providing new perspectives for establishing powerful biomarkers of aging.

In this article, the role of DNA methylation in aging and longevity has been reviewed by analysing literature data about DNA methylation variations occurring during the lifetime in response to environmental factors and genetic background, and their association with the aging process and, in particular, with the quality of aging. Special attention has been devoted to the relationship between nuclear DNA methylation patterns, mitochondrial DNA epigenetic modifications, and longevity. Mitochondrial DNA has recently been reported to modulate global DNA methylation levels of the nuclear genome during the lifetime, and, in spite of the previous belief, it has been found to be the target of methylation modifications.

Analysis of DNA methylation profiles across lifetime shows that a remodeling of the methylome occurs with age and/or with age-related decline. Thus, it can be an excellent biomarker of aging and of the individual decline and frailty status. The knowledge about the mechanisms underlying these modifications is crucial since it might allow the opportunity for targeted treatment to modulate the rate of aging and longevity.

Keywords: Aging, longevity, DNA methylation, mitochondrial DNA methylation, epigenetic clock, nutrition.

Kennedy BK, Berger SL, Brunet A, et al. Geroscience: linking aging to chronic disease. Cell 2014; 159(4): 709-13.
[] [PMID: 25417146]
Huang B, Jiang C, Zhang R. Epigenetics: the language of the cell? Epigenomics 2014; 6(1): 73-88.
[] [PMID: 24579948]
Allis CD, Jenuwein T. The molecular hallmarks of epigenetic control. Nat Rev Genet 2016; 17(8): 487-500.
[] [PMID: 27346641]
Barros SP, Offenbacher S. Epigenetics: connecting environment and genotype to phenotype and disease. J Dent Res 2009; 88(5): 400-8.
[] [PMID: 19493882]
Robertson KD. DNA methylation and human disease. Nat Rev Genet 2005; 6(8): 597-610.
[] [PMID: 16136652]
Liu L, Jin G, Zhou X. Modeling the relationship of epigenetic modifications to transcription factor binding. Nucleic Acids Res 2015; 43(8): 3873-85.
[] [PMID: 25820421]
Okano M, Bell DW, Haber DA, Li E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 1999; 99(3): 247-57.
[] [PMID: 10555141]
Lyko F. The DNA methyltransferase family: a versatile toolkit for epigenetic regulation. Nat Rev Genet 2018; 19(2): 81-92.
[] [PMID: 29033456]
Laisné M, Gupta N, Kirsh O, Pradhan S, Defossez PA. Mechanisms of DNA methyltransferase recruitment in mammals. Genes (Basel) 2018; 9(12)E617
[] [PMID: 30544749]
Tan L, Shi YG. Tet family proteins and 5-hydroxymethylcytosine in development and disease. Development 2012; 139(11): 1895-902.
[] [PMID: 22569552]
Wu X, Zhang Y. TET-mediated active DNA demethylation: mechanism, function and beyond. Nat Rev Genet 2017; 18(9): 517-34.
[] [PMID: 28555658]
Luo G-Z, Blanco MA, Greer EL, He C, Shi Y. DNA N(6)-methyladenine: a new epigenetic mark in eukaryotes? Nat Rev Mol Cell Biol 2015; 16(12): 705-10.
[] [PMID: 26507168]
Xiao CL, Zhu S, He M, et al. N6-methyladenine DNA modification in the human genome. Mol Cell 2018; 71(2): 306-18.e7.
[] [PMID: 30017583]
Pinney SE. Mammalian non-CpG methylation: stem cells and beyond. Biology (Basel) 2014; 3(4): 739-51.
[] [PMID: 25393317]
Lee JH, Park SJ, Nakai K. Differential landscape of non-CpG methylation in embryonic stem cells and neurons caused by DNMT3s. Sci Rep 2017; 7(1): 11295.
[] [PMID: 28900200]
Deaton AM, Bird A. CpG islands and the regulation of transcription. Genes Dev 2011; 25(10): 1010-22.
[] [PMID: 21576262]
Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 2012; 13(7): 484-92.
[] [PMID: 22641018]
Jeziorska DM, Murray RJS, De Gobbi M, et al. DNA methylation of intragenic CpG islands depends on their transcriptional activity during differentiation and disease. Proc Natl Acad Sci USA 2017; 114(36): E7526-35.
[] [PMID: 28827334]
Bellizzi D, D’Aquila P, Scafone T, et al. The control region of mitochondrial DNA shows an unusual CpG and non-CpG methylation pattern. DNA Res 2013; 20(6): 537-47.
[] [PMID: 23804556]
Iacobazzi V, Castegna A, Infantino V, Andria G. Mitochondrial DNA methylation as a next-generation biomarker and diagnostic tool. Mol Genet Metab 2013; 110(1-2): 25-34.
[] [PMID: 23920043]
D’Aquila P, Giordano M, Montesanto A, De Rango F, Passarino G, Bellizzi D. Age-and gender-related pattern of methylation in the MT-RNR1 gene. Epigenomics 2015; 7(5): 707-16.
[] [PMID: 26343273]
Liu B, Du Q, Chen L, et al. CpG methylation patterns of human mitochondrial DNA. Sci Rep 2016; 6: 23421.
[] [PMID: 26996456]
D’Aquila P, Montesanto A, Guarasci F, Passarino G, Bellizzi D. Mitochondrial genome and epigenome: two sides of the same coin. Front Biosci 2017; 22: 888-908.
[] [PMID: 27814653]
Whitelaw NC, Whitelaw E. How lifetimes shape epigenotype within and across generations. Hum Mol Genet 2006; 15(Spec No 2): R131-7.
[] [PMID: 16987876]
Kanherkar RR, Bhatia-Dey N, Csoka AB. Epigenetics across the human lifespan. Front Cell Dev Biol 2014; 2: 49.
[] [PMID: 25364756]
Montesanto A, Dato S, Bellizzi D, Rose G, Passarino G. Epidemiological, genetic and epigenetic aspects of the research on healthy ageing and longevity. Immun Ageing 2012; 9(1): 6.
[] [PMID: 22524317]
Christensen K, Vaupel JW. Determinants of longevity: genetic, environmental and medical factors. J Intern Med 1996; 240(6): 333-41.
[] [PMID: 9010380]
Giuliani C, Pirazzini C, Delledonne M, et al. Centenarians as extreme phenotypes: An ecological perspective to get insight into the relationship between the genetics of longevity and age-associated diseases. Mech Ageing Dev 2017; 165(Pt B): 195-201.
D’Aquila P, Rose G, Bellizzi D, Passarino G. Epigenetics and aging. Maturitas 2013; 74(2): 130-6.
[] [PMID: 23245587]
Li Y, Tollefsbol TO. Age-related epigenetic drift and phenotypic plasticity loss: implications in prevention of age-related human diseases. Epigenomics 2016; 8(12): 1637-51.
[] [PMID: 27882781]
Issa JP. Aging and epigenetic drift: a vicious cycle. J Clin Invest 2014; 124(1): 24-9.
[] [PMID: 24382386]
Zampieri M, Ciccarone F, Calabrese R, Franceschi C, Bürkle A, Caiafa P. Reconfiguration of DNA methylation in aging. Mech Ageing Dev 2015; 151: 60-70.
[] [PMID: 25708826]
Martin GM. Epigenetic drift in aging identical twins. Proc Natl Acad Sci USA 2005; 102(30): 10413-4.
[] [PMID: 16027353]
Lipman T, Tiedje LB. Epigenetic differences arise during the lifetime of monozygotic twins. Am J Matern Nurs 2006; 31: 204.
Tan Q, Heijmans BT, Hjelmborg JV, Soerensen M, Christensen K, Christiansen L. Epigenetic drift in the aging genome: a ten-year follow-up in an elderly twin cohort. Int J Epidemiol 2016; 45(4): 1146-58.
[] [PMID: 27498152]
Fraga MF, Ballestar E, Paz MF, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA 2005; 102(30): 10604-9.
[] [PMID: 16009939]
Bjornsson HT, Sigurdsson MI, Fallin MD, et al. Intra-individual change over time in DNA methylation with familial clustering. JAMA 2008; 299(24): 2877-83.
[] [PMID: 18577732]
Wong CC, Caspi A, Williams B, et al. A longitudinal study of epigenetic variation in twins. Epigenetics 2010; 5(6): 516-26.
[] [PMID: 20505345]
Rakyan VK, Down TA, Maslau S, et al. Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains. Genome Res 2010; 20(4): 434-9.
[] [PMID: 20219945]
Vijg J, Dollé ME. Genome instability: cancer or aging? Mech Ageing Dev 2007; 128(7-8): 466-8.
[] [PMID: 17617443]
Bollati V, Schwartz J, Wright R, et al. Decline in genomic DNA methylation through aging in a cohort of elderly subjects. Mech Ageing Dev 2009; 130(4): 234-9.
[] [PMID: 19150625]
Luo Y, Lu X, Xie H. Dynamic Alu methylation during normal development, aging, and tumorigenesis. BioMed Res Int 2014; 2014784706
[] [PMID: 25243180]
Heyn H, Li N, Ferreira HJ, et al. Distinct DNA methylomes of newborns and centenarians. Proc Natl Acad Sci USA 2012; 109(26): 10522-7.
[] [PMID: 22689993]
Gentilini D, Mari D, Castaldi D, et al. Role of epigenetics in human aging and longevity: genome-wide DNA methylation profile in centenarians and centenarians’ offspring. Age (Dordr) 2013; 35(5): 1961-73.
[] [PMID: 22923132]
McClay JL, Aberg KA, Clark SL, et al. 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 2014; 23(5): 1175-85.
[] [PMID: 24135035]
Florath I, Butterbach K, Müller H, Bewerunge-Hudler M, Brenner H. Cross-sectional and longitudinal changes in DNA methylation with age: an epigenome-wide analysis revealing over 60 novel age-associated CpG sites. Hum Mol Genet 2014; 23(5): 1186-201.
[] [PMID: 24163245]
Ashapkin VV, Kutueva LI, Vanyushin BF. Aging as an epigenetic phenomenon. Curr Genomics 2017; 18(5): 385-407.
[] [PMID: 29081695]
Reynolds LM, Taylor JR, Ding J, et al. Age-related variations in the methylome associated with gene expression in human monocytes and T cells. Nat Commun 2014; 5: 5366.
[] [PMID: 25404168]
Matsubayashi H, Sato N, Brune K, et al. Age- and disease-related methylation of multiple genes in nonneoplastic duodenum and in duodenal juice. Clin Cancer Res 2005; 11(2 Pt 1): 573-83.
[PMID: 15701843]
Porter LF, Saptarshi N, Fang Y, et al. Whole-genome methylation profiling of the retinal pigment epithelium of individuals with age-related macular degeneration reveals differential methylation of the SKI, GTF2H4, and TNXB genes. Clin Epigenetics 2019; 11(1): 6.
[] [PMID: 30642396]
Issa JP, Vertino PM, Boehm CD, Newsham IF, Baylin SB. Switch from monoallelic to biallelic human IGF2 promoter methylation during aging and carcinogenesis. Proc Natl Acad Sci USA 1996; 93(21): 11757-62.
[] [PMID: 8876210]
Christensen BC, Houseman EA, Marsit CJ, et al. Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet 2009; 5(8)e1000602
[] [PMID: 19680444]
Ahuja N, Li Q, Mohan AL, Baylin SB, Issa JP. Aging and DNA methylation in colorectal mucosa and cancer. Cancer Res 1998; 58(23): 5489-94.
[PMID: 9850084]
Maegawa S, Hinkal G, Kim HS, et al. Widespread and tissue specific age-related DNA methylation changes in mice. Genome Res 2010; 20(3): 332-40.
[] [PMID: 20107151]
Silva PN, Gigek CO, Leal MF, et al. Promoter methylation analysis of SIRT3, SMARCA5, HTERT and CDH1 genes in aging and Alzheimer’s disease. J Alzheimers Dis 2008; 13(2): 173-6.
[] [PMID: 18376059]
Nakagawa H, Nuovo GJ, Zervos EE, et al. Age-related hypermethylation of the 5′ region of MLH1 in normal colonic mucosa is associated with microsatellite-unstable colorectal cancer development. Cancer Res 2001; 61(19): 6991-5.
[PMID: 11585722]
Madrigano J, Baccarelli A, Mittleman MA, et al. Aging and epigenetics: longitudinal changes in gene-specific DNA methylation. Epigenetics 2012; 7(1): 63-70.
[] [PMID: 22207354]
Tohgi H, Utsugisawa K, Nagane Y, Yoshimura M, Genda Y, Ukitsu M. Reduction with age in methylcytosine in the promoter region -224 approximately -101 of the amyloid precursor protein gene in autopsy human cortex. Brain Res Mol Brain Res 1999; 70(2): 288-92.
[] [PMID: 10407177]
Fuso A, Seminara L, Cavallaro RA, D’Anselmi F, Scarpa S. S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production. Mol Cell Neurosci 2005; 28(1): 195-204.
[] [PMID: 15607954]
Rönn T, Poulsen P, Hansson O, et al. Age influences DNA methylation and gene expression of COX7A1 in human skeletal muscle. Diabetologia 2008; 51(7): 1159-68.
[] [PMID: 18488190]
Garagnani P, Bacalini MG, Pirazzini C, et al. Methylation of ELOVL2 gene as a new epigenetic marker of age. Aging Cell 2012; 11(6): 1132-4.
[] [PMID: 23061750]
Kim SJ, Chun M, Wan J, Lee C, Yen K, Cohen P. GRSF1 is an age-related regulator of senescence. Sci Rep 2019; 9(1): 5546.
[] [PMID: 30944385]
Yeh SH, Liu CL, Chang RC, Wu CC, Lin CH, Yang KD. Aging-dependent DNA hypermethylation and gene expression of GSTM1 involved in T cell differentiation. Oncotarget 2017; 8(30): 48591-602.
[] [PMID: 28596482]
Bell JT, Tsai PC, Yang TP, et al. Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population. PLoS Genet 2012; 8(4)e1002629
[] [PMID: 22532803]
D’Aquila P, Montesanto A, De Rango F, Guarasci F, Passarino G, Bellizzi D. Epigenetic signature: implications for mitochondrial quality control in human aging. Aging (Albany NY) 2019; 11(4): 1240-51.
[] [PMID: 30787202]
Mawlood SK, Dennany L, Watson N, Dempster J, Pickard BS. Quantification of global mitochondrial DNA methylation levels and inverse correlation with age at two CpG sites. Aging (Albany NY) 2016; 8(4): 636-41.
[] [PMID: 26887692]
D’Aquila P, Montesanto A, Mandalà M, et al. Methylation of the ribosomal RNA gene promoter is associated with aging and age-related decline. Aging Cell 2017; 16(5): 966-75.
[] [PMID: 28625020]
D’Aquila P, Bellizzi D, Passarino G. rRNA-gene methylation and biological aging. Aging (Albany NY) 2018; 10(1): 7-8.
[] [PMID: 29365326]
Wang M, Lemos B. Ribosomal DNA harbors an evolutionarily conserved clock of biological aging. Genome Res 2019; 29(3): 325-33.
[] [PMID: 30765617]
Choi EK, Uyeno S, Nishida N, et al. Alterations of c-fos gene methylation in the processes of aging and tumorigenesis in human liver. Mutat Res 1996; 354(1): 123-8.
[] [PMID: 8692198]
Gaudet MM, Campan M, Figueroa JD, et al. DNA hypermethylation of ESR1 and PGR in breast cancer: pathologic and epidemiologic associations. Cancer Epidemiol Biomarkers Prev 2009; 18(11): 3036-43.
[] [PMID: 19861523]
Zbieć-Piekarska R, Spólnicka M, Kupiec T, et al. Development of a forensically useful age prediction method based on DNA methylation analysis. Forensic Sci Int Genet 2015; 17: 173-9.
[] [PMID: 26026729]
Virmani AK, Rathi A, Sathyanarayana UG, et al. Aberrant methylation of the Adenomatous polyposis coli (APC) gene promoter 1A in breast and lung carcinomas. Clin Cancer Res 2001; 7(7): 1998-2004.
[PMID: 11448917]
Waki T, Tamura G, Sato M, Motoyama T. Age-related methylation of tumor suppressor and tumor-related genes: an analysis of autopsy samples. Oncogene 2003; 22(26): 4128-33.
[] [PMID: 12821947]
Fujii H, Biel MA, Zhou W, Weitzman SA, Baylin SB, Gabrielson E. Methylation of the HIC-1 candidate tumor suppressor gene in human breast cancer. Oncogene 1998; 16(16): 2159-64.
[] [PMID: 9572497]
Nishida N, Nagasaka T, Nishimura T, Ikai I, Boland CR, Goel A. Aberrant methylation of multiple tumor suppressor genes in aging liver, chronic hepatitis, and hepatocellular carcinoma. Hepatology 2008; 47(3): 908-18.
[] [PMID: 18161048]
So K, Tamura G, Honda T, et al. Multiple tumor suppressor genes are increasingly methylated with age in non-neoplastic gastric epithelia. Cancer Sci 2006; 97(11): 1155-8.
[] [PMID: 16952303]
Cody DT II, Huang Y, Darby CJ, Johnson GK, Domann FE. Differential DNA methylation of the p16 INK4A/CDKN2A promoter in human oral cancer cells and normal human oral keratinocytes. Oral Oncol 1999; 35(5): 516-22.
[] [PMID: 10694953]
López V, Fernández AF, Fraga MF. The role of 5-hydroxymethylcytosine in development, aging and age-related diseases. Ageing Res Rev 2017; 37: 28-38.
[] [PMID: 28499883]
Szulwach KE, Li X, Li Y, et al. 5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging. Nat Neurosci 2011; 14(12): 1607-16.
[] [PMID: 22037496]
Chen H, Dzitoyeva S, Manev H. Effect of aging on 5-hydroxymethylcytosine in the mouse hippocampus. Restor Neurol Neurosci 2012; 30(3): 237-45.
[PMID: 22426040]
Valentini E, Zampieri M, Malavolta M, et al. Analysis of the machinery and intermediates of the 5hmC-mediated DNA demethylation pathway in aging on samples from the MARK-AGE Study. Aging (Albany NY) 2016; 8(9): 1896-922.
[] [PMID: 27587280]
Buscarlet M, Tessier A, Provost S, Mollica L, Busque L. Human blood cell levels of 5-hydroxymethylcytosine (5hmC) decline with age, partly related to acquired mutations in TET2. Exp Hematol 2016; 44(11): 1072-84.
[] [PMID: 27475703]
Trifunovic A. Mitochondrial DNA and ageing. Biochim Biophys Acta 2006; 1757(5-6): 611-7.
[] [PMID: 16624248]
Minocherhomji S, Tollefsbol TO, Singh KK. Mitochondrial regulation of epigenetics and its role in human diseases. Epigenetics 2012; 7(4): 326-34.
[] [PMID: 22419065]
Ramani K, Lu SC. Methionine adenosyltransferases in liver health and diseases. Liver Res 2017; 1(2): 103-11.
[] [PMID: 29170720]
Matilainen O, Quirós PM, Auwerx J. Mitochondria and epigenetics - crosstalk in homeostasis and stress. Trends Cell Biol 2017; 27(6): 453-63.
[] [PMID: 28274652]
Smiraglia DJ, Kulawiec M, Bistulfi GL, Gupta SG, Singh KK. A novel role for mitochondria in regulating epigenetic modification in the nucleus. Cancer Biol Ther 2008; 7(8): 1182-90.
[] [PMID: 18458531]
Bellizzi D, D’Aquila P, Giordano M, Montesanto A, Passarino G. Global DNA methylation levels are modulated by mitochondrial DNA variants. Epigenomics 2012; 4(1): 17-27.
[] [PMID: 22332655]
Shmookler Reis RJ, Goldstein S. Mitochondrial DNA in mortal and immortal human cells. Genome number, integrity, and methylation. J Biol Chem 1983; 258(15): 9078-85.
[PMID: 6307991]
Dzitoyeva S, Chen H, Manev H. Effect of aging on 5-hydroxymethylcytosine in brain mitochondria. Neurobiol Aging 2012; 33(12): 2881-91.
[] [PMID: 22445327]
D’Aquila P, Bellizzi D, Passarino G. Mitochondria in health, aging and diseases: the epigenetic perspective. Biogerontology 2015; 16(5): 569-85.
[] [PMID: 25711915]
Bocklandt S, Lin W, Sehl ME, et al. Epigenetic predictor of age. PLoS One 2011; 6(6)e14821
[] [PMID: 21731603]
Bellizzi D, D’Aquila P, Montesanto A, et al. Global DNA methylation in old subjects is correlated with frailty. Age (Dordr) 2012; 34(1): 169-79.
[] [PMID: 21336567]
Zheng SC, Widschwendter M, Teschendorff AE. Epigenetic drift, epigenetic clocks and cancer risk. Epigenomics 2016; 8(5): 705-19.
[] [PMID: 27104983]
Levine ME, Lu AT, Quach A, et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY) 2018; 10(4): 573-91.
[] [PMID: 29676998]
Montesanto A, Lagani V, Martino C, et al. A novel, population-specific approach to define frailty. Age (Dordr) 2010; 32(3): 385-95.
[] [PMID: 20640550]
Kim S, Jazwinski SM. Quantitative measures of healthy aging and biological age. Healthy Aging Res 2015; 4: 26.
[PMID: 26005669]
Montesanto A, De Rango F, Pirazzini C, et al. Demographic, genetic and phenotypic characteristics of centenarians in Italy: focus on gender differences Mech Ageing Dev 2017; 165(Pt B): 68-74.
[] [PMID: 28461103]
Gravina S, Vijg J. Epigenetic factors in aging and longevity. Pflugers Arch 2010; 459(2): 247-58.
[] [PMID: 19768466]
Horvath S. DNA methylation age of human tissues and cell types. Genome Biol 2013; 14(10): R115.
[] [PMID: 24138928]
Hannum G, Guinney J, Zhao L, et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell 2013; 49(2): 359-67.
[] [PMID: 23177740]
Marioni RE, Shah S, McRae AF, et al. DNA methylation age of blood predicts all-cause mortality in later life. Genome Biol 2015; 16: 25.
[] [PMID: 25633388]
Christiansen L, Lenart A, Tan Q, et al. DNA methylation age is associated with mortality in a longitudinal Danish twin study. Aging Cell 2016; 15(1): 149-54.
[] [PMID: 26594032]
Perna L, Zhang Y, Mons U, Holleczek B, Saum KU, Brenner H. Epigenetic age acceleration predicts cancer, cardiovascular, and all-cause mortality in a German case cohort. Clin Epigenetics 2016; 8: 64.
[] [PMID: 27274774]
Bacalini MG, D’Aquila P, Marasco E, et al. The methylation of nuclear and mitochondrial DNA in ageing phenotypes and longevity Mech Ageing Dev 2017; 165(Pt B): 156-61.
[] [PMID: 28115210]
Horvath S, Pirazzini C, Bacalini MG, et al. Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring. Aging (Albany NY) 2015; 7(12): 1159-70.
[] [PMID: 26678252]
Horvath S, Garagnani P, Bacalini MG, et al. Accelerated epigenetic aging in Down syndrome. Aging Cell 2015; 14(3): 491-5.
[] [PMID: 25678027]
Zheng Y, Joyce BT, Colicino E, et al. Blood epigenetic age may predict cancer incidence and mortality. EBioMedicine 2016; 5: 68-73.
[] [PMID: 27077113]
Breitling LP, Saum KU, Perna L, Schöttker B, Holleczek B, Brenner H. Frailty is associated with the epigenetic clock but not with telomere length in a German cohort. Clin Epigenetics 2016; 8: 21.
[] [PMID: 26925173]
Lu AT, Quach A, Wilson JG, et al. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging (Albany NY) 2019; 11(2): 303-27.
[] [PMID: 30669119]
Hannon E, Knox O, Sugden K, et al. Characterizing genetic and environmental influences on variable DNA methylation using monozygotic and dizygotic twins. PLoS Genet 2018; 14(8)e1007544
[] [PMID: 30091980]
Martin EM, Fry RC. Environmental Influences on the Epigenome: exposure-associated DNA methylation in human populations. Annu Rev Public Health 2018; 39: 309-33.
[] [PMID: 29328878]
de F C Lichtenfels AJ, van der Plaat DA, de Jong K, et al. Long-term air pollution exposure, genome-wide DNA methylation and lung function in the LifeLines Cohort Study. Environ Health Perspect 2018; 126(2)027004
[] [PMID: 29410382]
Fang M, Chen D, Yang CS. Dietary polyphenols may affect DNA methylation. J Nutr 2007; 137(1)(Suppl.): 223S-8S.
[] [PMID: 17182830]
Lee KW, Pausova Z. Cigarette smoking and DNA methylation. Front Genet 2013; 4: 132.
[] [PMID: 23882278]
Sillanpää E, Ollikainen M, Kaprio J, et al. Leisure-time physical activity and DNA methylation age-a twin study. Clin Epigenetics 2019; 11(1): 12.
[] [PMID: 30660189]
Lambrou A, Baccarelli A, Wright RO, et al. Arsenic exposure and DNA methylation among elderly men. Epidemiology 2012; 23(5): 668-76.
[] [PMID: 22833016]
Sae-Lee C, Corsi S, Barrow TM, et al. Dietary intervention modifies DNA methylation age assessed by the epigenetic clock. Mol Nutr Food Res 2018; 62(23)e1800092
[] [PMID: 30350398]
Ryan J, Wrigglesworth J, Loong J, Fransquet PD, Woods RL. A systematic review and meta-analysis of environmental, lifestyle and health factors associated with DNA methylation age. J Gerontol A Biol Sci Med Sci 2019.pii: glz099
[] [PMID: 31001624]
Zhang N. Role of methionine on epigenetic modification of DNA methylation and gene expression in animals. Anim Nutr 2018; 4(1): 11-6.
[] [PMID: 30167479]
McKay JA, Mathers JC. Diet induced epigenetic changes and their implications for health. Acta Physiol (Oxf) 2011; 202(2): 103-18.
[] [PMID: 21401888]
Sinclair KD, Lea RG, Rees WD, Young LE. The developmental origins of health and disease: current theories and epigenetic mechanisms. Soc Reprod Fertil Suppl 2007; 64: 425-43.
[] [PMID: 17491163]
Lillycrop KA, Hoile SP, Grenfell L, Burdge GC. DNA methylation, ageing and the influence of early life nutrition. Proc Nutr Soc 2014; 73(3): 413-21.
[] [PMID: 25027290]
Vickers MH. Early life nutrition, epigenetics and programming of later life disease. Nutrients 2014; 6(6): 2165-78.
[] [PMID: 24892374]
Wu Y, Cheng Z, Bai Y, Ma X. Epigenetic mechanisms of maternal dietary protein and amino acids affecting growth and development of offspring. Curr Protein Pept Sci 2019; 20(7): 727-35.
[] [PMID: 30678627]
Park JH, Kim SH, Lee MS, Kim MS. Epigenetic modification by dietary factors: implications in metabolic syndrome. Mol Aspects Med 2017; 54: 58-70.
[] [PMID: 28216432]
Pauwels S, Ghosh M, Duca RC, et al. Maternal intake of methyl-group donors affects DNA methylation of metabolic genes in infants. Clin Epigenetics 2017; 9: 16.
[] [PMID: 28191262]
Heijmans BT, Tobi EW, Stein AD, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci USA 2008; 105(44): 17046-9.
[] [PMID: 18955703]
Tobi EW, Lumey LH, Talens RP, et al. DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum Mol Genet 2009; 18(21): 4046-53.
[] [PMID: 19656776]
Tobi EW, Goeman JJ, Monajemi R, et al. DNA methylation signatures link prenatal famine exposure to growth and metabolism. Nat Commun 2014; 5: 5592.
[] [PMID: 25424739]
Guarasci F, D’Aquila P, Mandalà M, et al. Aging and nutrition induce tissue-specific changes on global DNA methylation status in rats. Mech Ageing Dev 2018; 174: 47-54.
[] [PMID: 29427568]
Athanasopoulos D, Karagiannis G, Tsolaki M. Recent findings in Alzheimer disease and nutrition focusing on epigenetics. Adv Nutr 2016; 7(5): 917-27.
[] [PMID: 27633107]
Román GC, Mancera-Páez O, Bernal C. Epigenetic factors in late-onset Alzheimer’s disease: MTHFR and CTH gene polymorphisms, metabolic transsulfuration and methylation pathways, and B vitamins. Int J Mol Sci 2019; 20(2)E319
[] [PMID: 30646578]
Fuso A, Nicolia V, Ricceri L, et al. S-adenosylmethionine reduces the progress of the Alzheimer-like features induced by B-vitamin deficiency in mice. Neurobiol Aging 2012; 33(7): 1482.e1-e16.
[] [PMID: 22221883]
Petkovich DA, Podolskiy DI, Lobanov AV, Lee SG, Miller RA, Gladyshev VN. Using DNA methylation profiling to evaluate biological age and longevity interventions. Cell Metab 2017; 25(4): 954-960.e6.
[] [PMID: 28380383]
Wang T, Tsui B, Kreisberg JF, et al. Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment. Genome Biol 2017; 18(1): 57.
[] [PMID: 28351423]
Gensous N, Franceschi C, Santoro A, Milazzo M, Garagnani P, Bacalini MG. The impact of caloric restriction on the epigenetic signatures of aging. Int J Mol Sci 2019; 20(8)E2022
[] [PMID: 31022953]
Maegawa S, Lu Y, Tahara T, et al. Caloric restriction delays age-related methylation drift. Nat Commun 2017; 8(1): 539.
[] [PMID: 28912502]
Kirchner H, Osler ME, Krook A, Zierath JR. Epigenetic flexibility in metabolic regulation: disease cause and prevention? Trends Cell Biol 2013; 23(5): 203-9.
[] [PMID: 23277089]
Remely M, Lovrecic L, de la Garza AL, et al. Therapeutic perspectives of epigenetically active nutrients. Br J Pharmacol 2015; 172(11): 2756-68.
[] [PMID: 25046997]
Fang MZ, Wang Y, Ai N, et al. Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res 2003; 63(22): 7563-70.
[PMID: 14633667]
Fang MZ, Chen D, Sun Y, Jin Z, Christman JK, Yang CS. Reversal of hypermethylation and reactivation of p16INK4a, RARbeta, and MGMT genes by genistein and other isoflavones from soy. Clin Cancer Res 2005; 11(19 Pt 1): 7033-41.
[] [PMID: 16203797]
Meeran SM, Patel SN, Tollefsbol TO. Sulforaphane causes epigenetic repression of hTERT expression in human breast cancer cell lines. PLoS One 2010; 5(7)e11457
[] [PMID: 20625516]
Greco T, Shafer J, Fiskum G. Sulforaphane inhibits mitochondrial permeability transition and oxidative stress. Free Radic Biol Med 2011; 51(12): 2164-71.
[] [PMID: 21986339]
Hardy TM, Tollefsbol TO. Epigenetic diet: impact on the epigenome and cancer. Epigenomics 2011; 3(4): 503-18.
[] [PMID: 22022340]
Daniel M, Tollefsbol TO. Epigenetic linkage of aging, cancer and nutrition. J Exp Biol 2015; 218(Pt 1): 59-70.
[] [PMID: 25568452]
Lillycrop KA, Phillips ES, Jackson AA, Hanson MA, Burdge GC. Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. J Nutr 2005; 135(6): 1382-6.
[] [PMID: 15930441]
Lillycrop KA, Phillips ES, Torrens C, Hanson MA, Jackson AA, Burdge GC. Feeding pregnant rats a protein-restricted diet persistently alters the methylation of specific cytosines in the hepatic PPAR alpha promoter of the offspring. Br J Nutr 2008; 100(2): 278-82.
[] [PMID: 18186951]
Howard TD, Ho SM, Zhang L, et al. Epigenetic changes with dietary soy in cynomolgus monkeys. PLoS One 2011; 6(10)e26791
[] [PMID: 22046358]
Boqué N, de la Iglesia R, de la Garza AL, et al. Prevention of diet-induced obesity by apple polyphenols in Wistar rats through regulation of adipocyte gene expression and DNA methylation patterns. Mol Nutr Food Res 2013; 57(8): 1473-8.
[] [PMID: 23529981]
Szarc vel Szic K, Declerck K, Vidaković M, Vanden Berghe W. From inflammaging to healthy aging by dietary lifestyle choices: is epigenetics the key to personalized nutrition? Clin Epigenetics 2015; 7: 33.
[] [PMID: 25861393]
Szarc vel Szic K, Ndlovu MN, Haegeman G, Vanden Berghe W. Nature or nurture: let food be your epigenetic medicine in chronic inflammatory disorders. Biochem Pharmacol 2010; 80(12): 1816-32.
[] [PMID: 20688047]
Xu Z, Li H, Jin P. Epigenetics-based therapeutics for neurodegenerative disorders. Curr Transl Geriatr Exp Gerontol Rep 2012; 1(4): 229-36.
[] [PMID: 23526405]
Liu X, Jiao B, Shen L. The epigenetics of Alzheimer’s disease: factors and therapeutic implications. Front Genet 2018; 9: 579.
[] [PMID: 30555513]
Mastroeni D, Grover A, Delvaux E, Whiteside C, Coleman PD, Rogers J. Epigenetic changes in Alzheimer’s disease: decrements in DNA methylation. Neurobiol Aging 2010; 31(12): 2025-37.
[] [PMID: 19117641]
Essa MM, Vijayan RK, Castellano-Gonzalez G, Memon MA, Braidy N, Guillemin GJ. Neuroprotective effect of natural products against Alzheimer’s disease. Neurochem Res 2012; 37(9): 1829-42.
[] [PMID: 22614926]
Ebrahimi A, Schluesener H. Natural polyphenols against neurodegenerative disorders: potentials and pitfalls. Ageing Res Rev 2012; 11(2): 329-45.
[] [PMID: 22336470]
Fuso A, Nicolia V, Cavallaro RA, Scarpa S. DNA methylase and demethylase activities are modulated by one-carbon metabolism in Alzheimer’s disease models. J Nutr Biochem 2011; 22(3): 242-51.
[] [PMID: 20573497]
Ivanov M, Kacevska M, Ingelman-Sundberg M. Epigenomics and interindividual differences in drug response. Clin Pharmacol Ther 2012; 92(6): 727-36.
[] [PMID: 23093317]

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