{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:30:09Z","timestamp":1791433809245,"version":"4.3.3"},"reference-count":254,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T00:00:00Z","timestamp":1714953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["23-75-01141"],"award-info":[{"award-number":["23-75-01141"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vitamin B12 (cobalamin) is an essential nutrient for humans and animals. Metabolically active forms of B12-methylcobalamin and 5-deoxyadenosylcobalamin are cofactors for the enzymes methionine synthase and mitochondrial methylmalonyl-CoA mutase. Malfunction of these enzymes due to a scarcity of vitamin B12 leads to disturbance of one-carbon metabolism and impaired mitochondrial function. A significant fraction of the population (up to 20%) is deficient in vitamin B12, with a higher rate of deficiency among elderly people. B12 deficiency is associated with numerous hallmarks of aging at the cellular and organismal levels. Cellular senescence is characterized by high levels of DNA damage by metabolic abnormalities, increased mitochondrial dysfunction, and disturbance of epigenetic regulation. B12 deficiency could be responsible for or play a crucial part in these disorders. In this review, we focus on a comprehensive analysis of molecular mechanisms through which vitamin B12 influences aging. We review new data about how deficiency in vitamin B12 may accelerate cellular aging. Despite indications that vitamin B12 has an important role in health and healthy aging, knowledge of the influence of vitamin B12 on aging is still limited and requires further research.<\/jats:p>","DOI":"10.3390\/ijms25095044","type":"journal-article","created":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T15:05:01Z","timestamp":1715007901000},"page":"5044","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Emerging Roles of Vitamin B12 in Aging and Inflammation"],"prefix":"10.3390","volume":"25","author":[{"given":"Sergey Yu.","family":"Simonenko","sequence":"first","affiliation":[{"name":"Research Center for Translational Medicine, Sirius University of Science and Technology, 354340 Sochi, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2851-3775","authenticated-orcid":false,"given":"Daria A.","family":"Bogdanova","sequence":"additional","affiliation":[{"name":"Division of Immunobiology and Biomedicine, Center for Genetics and Life Sciences, Sirius University of Science and Technology, 354340 Sochi, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8718-7100","authenticated-orcid":false,"given":"Nikita A.","family":"Kuldyushev","sequence":"additional","affiliation":[{"name":"Research Center for Translational Medicine, Sirius University of Science and Technology, 354340 Sochi, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s13148-015-0154-5","article-title":"The Effects of Long-Term Daily Folic Acid and Vitamin B12 Supplementation on Genome-Wide DNA Methylation in Elderly Subjects","volume":"7","author":"Kok","year":"2015","journal-title":"Clin. Epigenet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"eabn4772","DOI":"10.1126\/scitranslmed.abn4772","article-title":"Aberrant Methylmalonylation Underlies Methylmalonic Acidemia and Is Attenuated by an Engineered Sirtuin","volume":"14","author":"Head","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.cmet.2014.10.002","article-title":"Vitamin B12 as a Modulator of Gut Microbial Ecology","volume":"20","author":"Degnan","year":"2014","journal-title":"Cell Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"13361","DOI":"10.1038\/s41598-021-92945-y","article-title":"Persistent Elevation of Plasma Vitamin B12 Is Strongly Associated with Solid Cancer","volume":"11","author":"Lacombe","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1002\/jsfa.12976","article-title":"Higher Circulating Vitamin B12 Is Associated with Lower Levels of Inflammatory Markers in Individuals at High Cardiovascular Risk and in Naturally Aged Mice","volume":"104","author":"Kovatcheva","year":"2024","journal-title":"J. Sci. Food Agric."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1177\/0004563212473279","article-title":"Vitamin B12 and Ageing: Current Issues and Interaction with Folate","volume":"50","author":"Hughes","year":"2013","journal-title":"Ann. Clin. Biochem."},{"key":"ref_7","first-page":"451","article-title":"B Vitamins and Ageing","volume":"Volume 90","author":"Harris","year":"2018","journal-title":"Biochemistry and Cell Biology of Ageing: Part I Biomedical Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1351\/pac197333010145","article-title":"The Total Synthesis of Vitamin B12","volume":"33","author":"Woodward","year":"1973","journal-title":"Pure Appl. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s00253-001-0902-7","article-title":"Microbial Production of Vitamin B12","volume":"58","author":"Martens","year":"2002","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.chom.2013.12.007","article-title":"Human Gut Microbes Use Multiple Transporters to Distinguish Vitamin B12 Analogs and Compete in the Gut","volume":"15","author":"Degnan","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e02117-19","DOI":"10.1128\/AEM.02117-19","article-title":"Comparative Genomics Guides Elucidation of Vitamin B12 Biosynthesis in Novel Human-Associated Akkermansia Strains","volume":"86","author":"Kirmiz","year":"2020","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Balabanova, L., Averianova, L., Marchenok, M., Son, O., and Tekutyeva, L. (2021). Microbial and Genetic Resources for Cobalamin (Vitamin B12) Biosynthesis: From Ecosystems to Industrial Biotechnology. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094522"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6446","DOI":"10.1021\/bi062063l","article-title":"Mechanisms of Discrimination between Cobalamins and Their Natural Analogues during Their Binding to the Specific B12-Transporting Proteins","volume":"46","author":"Fedosov","year":"2007","journal-title":"Biochemistry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nrgastro.2012.76","article-title":"Vitamin B12 Transport from Food to the Body\u2019s Cells\u2014A Sophisticated, Multistep Pathway","volume":"9","author":"Nielsen","year":"2012","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1182\/blood-2008-05-158949","article-title":"The Protein and the Gene Encoding the Receptor for the Cellular Uptake of Transcobalamin-Bound Cobalamin","volume":"113","author":"Quadros","year":"2009","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.molcel.2017.05.021","article-title":"Heterogeneous Ribosomes Preferentially Translate Distinct Subpools of MRNAs Genome-Wide","volume":"67","author":"Shi","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"F408","DOI":"10.1152\/ajprenal.00206.2000","article-title":"Megalin Is Essential for Renal Proximal Tubule Reabsorption and Accumulation of Transcobalamin-B12","volume":"282","author":"Birn","year":"2002","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/ng.294","article-title":"Identification of a Putative Lysosomal Cobalamin Exporter Altered in the CblF Defect of Vitamin B12 Metabolism","volume":"41","author":"Rutsch","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1038\/ng.2386","article-title":"Mutations in ABCD4 Cause a New Inborn Error of Vitamin B12 Metabolism","volume":"44","author":"Coelho","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"14551","DOI":"10.1073\/pnas.0805989105","article-title":"Decyanation of Vitamin B12 by a Trafficking Chaperone","volume":"105","author":"Kim","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.ymgme.2009.04.005","article-title":"Processing of Alkylcobalamins in Mammalian Cells: A Role for the MMACHC (CblC) Gene Product","volume":"97","author":"Hannibal","year":"2009","journal-title":"Mol. Genet. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"42742","DOI":"10.1074\/jbc.M407733200","article-title":"The CblD Defect Causes Either Isolated or Combined Deficiency of Methylcobalamin and Adenosylcobalamin Synthesis","volume":"279","author":"Suormala","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/nchembio.67","article-title":"Adenosyltransferase Tailors and Delivers Coenzyme B12","volume":"4","author":"Padovani","year":"2008","journal-title":"Nat. Chem. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"21567","DOI":"10.1073\/pnas.0908106106","article-title":"A G-Protein Editor Gates Coenzyme B12 Loading and Is Corrupted in Methylmalonic Aciduria","volume":"106","author":"Padovani","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Rodionov, D.A., Arzamasov, A.A., Khoroshkin, M.S., Iablokov, S.N., Leyn, S.A., Peterson, S.N., Novichkov, P.S., and Osterman, A.L. (2019). Micronutrient Requirements and Sharing Capabilities of the Human Gut Microbiome. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.01316"},{"key":"ref_26","first-page":"129714","article-title":"Systematic Genome Assessment of B-Vitamin Biosynthesis Suggests Co-Operation among Gut Microbes","volume":"6","author":"Ravcheev","year":"2015","journal-title":"Front. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1093\/ajcn\/68.2.328","article-title":"Role of Cobalamin Intake and Atrophic Gastritis in Mild Cobalamin Deficiency in Older Dutch Subjects","volume":"68","author":"Blom","year":"1998","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/jcsm.12260","article-title":"Vitamin B12 Deficiency and Impaired Expression of Amnionless during Aging","volume":"9","author":"Migliavacca","year":"2018","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Hodgson, N.W., Trivedi, M.S., Abdolmaleky, H.M., Fournier, M., Cuenod, M., Do, K.Q., and Deth, R.C. (2016). Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146797"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3249","DOI":"10.1016\/S0021-9258(18)97211-X","article-title":"Metabolism of Propionic Acid in Animal Tissues","volume":"240","author":"Cannata","year":"1965","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1111\/j.1365-2141.1975.tb00885.x","article-title":"Intracellular Localization of Hepatic Propionyl-CoA Carboxylase and Methylmalonyl-CoA Mutase in Humans and Normal and Vitamin B12 Deficient Rats","volume":"31","author":"Frenkel","year":"1975","journal-title":"Br. J. Haematol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1111\/j.1432-1033.1986.tb09614.x","article-title":"On the Mechanism of Action of Methylmalonyl-CoA Mutase. Change of the Steric Course on Isotope Substitution","volume":"156","author":"Wolfle","year":"1986","journal-title":"Eur. J. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"38204","DOI":"10.1074\/jbc.M110.177717","article-title":"Structures of the Human GTPase MMAA and Vitamin B12-Dependent Methylmalonyl-CoA Mutase and Insight into Their Complex Formation","volume":"285","author":"Froese","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1016\/j.bbapap.2012.03.012","article-title":"Adenosylcobalamin Enzymes: Theory and Experiment Begin to Converge","volume":"1824","author":"Marsh","year":"2012","journal-title":"Biochim. Biophys. Acta BBA Proteins Proteom."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.bbadis.2016.10.016","article-title":"Methionine Synthase and Methionine Synthase Reductase Interact with MMACHC and with MMADHC","volume":"1863","author":"Bassila","year":"2017","journal-title":"Biochim. Biophys. Acta BBA Mol. Basis Dis."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"The GTEx Consortium, Aguet, F., Anand, S., Ardlie, K.G., Gabriel, S., Getz, G.A., Graubert, A., Hadley, K., Handsaker, R.E., and Huang, K.H. (2020). The GTEx Consortium Atlas of Genetic Regulatory Effects across Human Tissues. Science, 369, 1318\u20131330.","DOI":"10.1126\/science.aaz1776"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"32662","DOI":"10.1074\/jbc.M501964200","article-title":"A B12-Responsive Internal Ribosome Entry Site (IRES) Element in Human Methionine Synthase","volume":"280","author":"Oltean","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3628","DOI":"10.1074\/jbc.272.6.3628","article-title":"Human Methionine Synthase","volume":"272","author":"Chen","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6365","DOI":"10.1038\/s41467-023-42037-4","article-title":"Structure of Full-Length Cobalamin-Dependent Methionine Synthase and Cofactor Loading Captured in Crystallo","volume":"14","author":"Mendoza","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e2302531120","DOI":"10.1073\/pnas.2302531120","article-title":"Conformational Switching and Flexibility in Cobalamin-Dependent Methionine Synthase Studied by Small-Angle X-Ray Scattering and Cryoelectron Microscopy","volume":"120","author":"Watkins","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nsb738","article-title":"Domain Alternation Switches B(12)-Dependent Methionine Synthase to the Activation Conformation","volume":"9","author":"Bandarian","year":"2002","journal-title":"Nat. Struct. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2464","DOI":"10.1021\/bi952389m","article-title":"Mutations in the B12-Binding Region of Methionine Synthase: How the Protein Controls Methylcobalamin Reactivity","volume":"35","author":"Jarrett","year":"1996","journal-title":"Biochemistry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"16044","DOI":"10.1021\/jp4093145","article-title":"Mechanistic Insights for Formation of an Organometallic Co\u2013C Bond in the Methyl Transfer Reaction Catalyzed by Methionine Synthase","volume":"117","author":"Kumar","year":"2013","journal-title":"J. Phys. Chem. B"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"13880","DOI":"10.1021\/bi001431x","article-title":"Protonation State of Methyltetrahydrofolate in a Binary Complex with Cobalamin-Dependent Methionine Synthase","volume":"39","author":"Smith","year":"2000","journal-title":"Biochemistry"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"9290","DOI":"10.1021\/bi00087a005","article-title":"Assignment of Enzymic Function to Specific Protein Regions of Cobalamin-Dependent Methionine Synthase from Escherichia Coli","volume":"32","author":"Drummond","year":"1993","journal-title":"Biochemistry"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1038\/s42255-021-00486-5","article-title":"Methionine Synthase Is Essential for Cancer Cell Proliferation in Physiological Folate Environments","volume":"3","author":"Sullivan","year":"2021","journal-title":"Nat. Metab."},{"key":"ref_47","unstructured":"West, A.A., Caudill, M.A., and Bailey, L.B. (2020). Present Knowledge in Nutrition, Elsevier."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"657","DOI":"10.2217\/epi.10.44","article-title":"Molecular Coupling of DNA Methylation and Histone Methylation","volume":"2","author":"Hashimoto","year":"2010","journal-title":"Epigenomics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/j.tem.2018.06.002","article-title":"Sink into the Epigenome: Histones as Repositories That Influence Cellular Metabolism","volume":"29","author":"Ye","year":"2018","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.molcel.2017.02.026","article-title":"A Metabolic Function for Phospholipid and Histone Methylation","volume":"66","author":"Ye","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1126\/science.1226603","article-title":"Influence of Threonine Metabolism on S -Adenosylmethionine and Histone Methylation","volume":"339","author":"Locasale","year":"2013","journal-title":"Science"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/sj.mp.4000522","article-title":"D4 Dopamine Receptor-Mediated Phospholipid Methylation and Its Implications for Mental Illnesses Such as Schizophrenia","volume":"4","author":"Sharma","year":"1999","journal-title":"Mol. Psychiatry"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41398-019-0630-3","article-title":"Methylation-Related Metabolic Effects of D4 Dopamine Receptor Expression and Activation","volume":"9","author":"Hodgson","year":"2019","journal-title":"Transl. Psychiatry"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Wang, X., and Pan, T. (2015). Methionine Mistranslation Bypasses the Restraint of the Genetic Code to Generate Mutant Proteins with Distinct Activities. PLoS Genet., 11.","DOI":"10.1371\/journal.pgen.1005745"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.bbagen.2013.04.038","article-title":"Methionine Oxidation and Reduction in Proteins","volume":"1840","author":"Kim","year":"2014","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0014-5793(99)00917-5","article-title":"Molecular Cloning and Functional Expression of a Human Peptide Methionine Sulfoxide Reductase (HMsrA)","volume":"456","author":"Kuschel","year":"1999","journal-title":"FEBS Lett."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1146\/annurev.bi.52.070183.003431","article-title":"Glutathione","volume":"52","author":"Meister","year":"1983","journal-title":"Annu. Rev. Biochem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/978-1-60761-756-3_18","article-title":"Measurement of Oxidized\/Reduced Glutathione Ratio","volume":"Volume 648","author":"Bross","year":"2010","journal-title":"Protein Misfolding and Cellular Stress in Disease and Aging"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Li, E., and Zhang, Y. (2014). DNA Methylation in Mammals. Cold Spring Harb. Perspect. Biol., 6.","DOI":"10.1101\/cshperspect.a019133"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1126\/science.6262918","article-title":"5-Methylcytosine in Eukaryotic DNA","volume":"212","author":"Ehrlich","year":"1981","journal-title":"Science"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1002\/ejic.202000898","article-title":"Formation of Cisplatin Adducts with the Epigenetically Relevant Nucleobase 5-Methylcytosine","volume":"2021","author":"Menke","year":"2021","journal-title":"Eur. J. Inorg. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5237","DOI":"10.1073\/pnas.97.10.5237","article-title":"Non-CpG Methylation Is Prevalent in Embryonic Stem Cells and May Be Mediated by DNA Methyltransferase 3a","volume":"97","author":"Ramsahoye","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nature17640","article-title":"DNA Methylation on N6-Adenine in Mammalian Embryonic Stem Cells","volume":"532","author":"Wu","year":"2016","journal-title":"Nature"},{"key":"ref_64","first-page":"85","article-title":"DNA N6-Methyladenine Epigenetic Modification Elevated in Human Esophageal Squamous Cell Carcinoma: A Potential Prognostic Marker","volume":"29","author":"Chen","year":"2020","journal-title":"Discov. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"110265","DOI":"10.1016\/j.ygeno.2022.01.002","article-title":"DNA N6-Methyladenine Involvement and Regulation of Hepatocellular Carcinoma Development","volume":"114","author":"Lin","year":"2022","journal-title":"Genomics"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/npp.2012.112","article-title":"DNA Methylation and Its Basic Function","volume":"38","author":"Moore","year":"2013","journal-title":"Neuropsychopharmacology"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Brenet, F., Moh, M., Funk, P., Feierstein, E., Viale, A.J., Socci, N.D., and Scandura, J.M. (2011). DNA Methylation of the First Exon Is Tightly Linked to Transcriptional Silencing. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0014524"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.ccr.2014.07.028","article-title":"Gene Body Methylation Can Alter Gene Expression and Is a Therapeutic Target in Cancer","volume":"26","author":"Yang","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Singh, A., Rappolee, D.A., and Ruden, D.M. (2023). Epigenetic Reprogramming in Mice and Humans: From Fertilization to Primordial Germ Cell Development. Cells, 12.","DOI":"10.3390\/cells12141874"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.mad.2008.12.003","article-title":"Decline in Genomic DNA Methylation through Aging in a Cohort of Elderly Subjects","volume":"130","author":"Bollati","year":"2009","journal-title":"Mech. Ageing Dev."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Kuznetsov, N.A., Kanazhevskaya, L.Y., and Fedorova, O.S. (2021). DNA Demethylation in the Processes of Repair and Epigenetic Regulation Performed by 2-Ketoglutarate-Dependent DNA Dioxygenases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910540"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ccr.2010.12.014","article-title":"Oncometabolite 2-Hydroxyglutarate Is a Competitive Inhibitor of \u03b1-Ketoglutarate-Dependent Dioxygenases","volume":"19","author":"Xu","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.cell.2016.09.038","article-title":"ALKBH1-Mediated TRNA Demethylation Regulates Translation","volume":"167","author":"Liu","year":"2016","journal-title":"Cell"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/acel.12047","article-title":"Genomes of Replicatively Senescent Cells Undergo Global Epigenetic Changes Leading to Gene Silencing and Activation of Transposable Elements","volume":"12","author":"Criscione","year":"2013","journal-title":"Aging Cell"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1042\/EBC20190039","article-title":"DNA Methylation Dynamics at Transposable Elements in Mammals","volume":"63","author":"Jansz","year":"2019","journal-title":"Essays Biochem."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Yang, Z., Xu, F., Wang, H., Teschendorff, A.E., Xie, F., and He, Y. (2021). Pan-Cancer Characterization of Long Non-Coding RNA and DNA Methylation Mediated Transcriptional Dysregulation. EBioMedicine, 68.","DOI":"10.1016\/j.ebiom.2021.103399"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"377","DOI":"10.4161\/cc.8.3.7526","article-title":"How Epigenetics Can Explain Human Metastasis: A New Role for MicroRNAs","volume":"8","author":"Lujambio","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.molonc.2012.07.007","article-title":"DNA Methylation and MicroRNA Dysregulation in Cancer","volume":"6","author":"Suzuki","year":"2012","journal-title":"Mol. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/bs.ircmb.2017.03.008","article-title":"Senescence-Associated MicroRNAs","volume":"334","author":"Munk","year":"2017","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Horvath, S. (2013). DNA Methylation Age of Human Tissues and Cell Types. Genome Biol., 14.","DOI":"10.1186\/gb-2013-14-10-r115"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.bbagrm.2014.03.001","article-title":"Interpreting the Language of Histone and DNA Modifications","volume":"1839","author":"Rothbart","year":"2014","journal-title":"Biochim. Biophys. Acta BBA Gene Regul. Mech."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1007\/s00109-010-0668-4","article-title":"Histone Methyltransferases: Regulation of Transcription and Contribution to Human Disease","volume":"88","author":"Nimura","year":"2010","journal-title":"J. Mol. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.cell.2007.05.009","article-title":"High-Resolution Profiling of Histone Methylations in the Human Genome","volume":"129","author":"Barski","year":"2007","journal-title":"Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2825","DOI":"10.1128\/MCB.02076-07","article-title":"DOT1L\/KMT4 Recruitment and H3K79 Methylation Are Ubiquitously Coupled with Gene Transcription in Mammalian Cells","volume":"28","author":"Steger","year":"2008","journal-title":"Mol. Cell. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.15252\/embr.201540945","article-title":"The Interplay of Histone Modifications\u2014Writers That Read","volume":"16","author":"Zhang","year":"2015","journal-title":"EMBO Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/s41556-023-01299-2","article-title":"Vitamin B12 Produced by Gut Bacteria Modulates Cholinergic Signalling","volume":"26","author":"Kang","year":"2024","journal-title":"Nat. Cell Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/ng.322","article-title":"Differential Chromatin Marking of Introns and Expressed Exons by H3K36me3","volume":"41","author":"Down","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/nature21373","article-title":"Intragenic DNA Methylation Prevents Spurious Transcription Initiation","volume":"543","author":"Neri","year":"2017","journal-title":"Nature"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/nature05987","article-title":"DNMT3L Connects Unmethylated Lysine 4 of Histone H3 to de Novo Methylation of DNA","volume":"448","author":"Ooi","year":"2007","journal-title":"Nature"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3375","DOI":"10.1093\/hmg\/ddp277","article-title":"Histone Methylation Is Mechanistically Linked to DNA Methylation at Imprinting Control Regions in Mammals","volume":"18","author":"Henckel","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1139\/O07-057","article-title":"Histone H3K4 Demethylases Are Essential in Development and Differentiation","volume":"85","author":"Benevolenskaya","year":"2007","journal-title":"Biochem. Cell Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1101\/gr.5704207","article-title":"The Landscape of Histone Modifications across 1% of the Human Genome in Five Human Cell Lines","volume":"17","author":"Koch","year":"2007","journal-title":"Genome Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"21931","DOI":"10.1073\/pnas.1016071107","article-title":"Histone H3K27ac Separates Active from Poised Enhancers and Predicts Developmental State","volume":"107","author":"Creyghton","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/ng.3550","article-title":"Histone H3 Globular Domain Acetylation Identifies a New Class of Enhancers","volume":"48","author":"Pradeepa","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1093\/nar\/gkg332","article-title":"The DNA Methyltransferases Associate with HP1 and the SUV39H1 Histone Methyltransferase","volume":"31","author":"Fuks","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1002\/jcb.22185","article-title":"Histone Deacetylase Inhibitors: Potential in Cancer Therapy","volume":"107","author":"Marks","year":"2009","journal-title":"J. Cell. Biochem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"31350","DOI":"10.1074\/jbc.C113.511261","article-title":"Activation of the Protein Deacetylase SIRT6 by Long-Chain Fatty Acids and Widespread Deacylation by Mammalian Sirtuins","volume":"288","author":"Feldman","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1126\/science.1207861","article-title":"Sirt5 Is a NAD-Dependent Protein Lysine Demalonylase and Desuccinylase","volume":"334","author":"Du","year":"2011","journal-title":"Science"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"M111.012658","DOI":"10.1074\/mcp.M111.012658","article-title":"The First Identification of Lysine Malonylation Substrates and Its Regulatory Enzyme","volume":"10","author":"Peng","year":"2011","journal-title":"Mol. Cell. Proteom."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"24","DOI":"10.5483\/BMBRep.2019.52.1.290","article-title":"Sirtuin Signaling in Cellular Senescence and Aging","volume":"52","author":"Lee","year":"2019","journal-title":"BMB Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.cell.2022.11.001","article-title":"Hallmarks of Aging: An Expanding Universe","volume":"186","author":"Blasco","year":"2023","journal-title":"Cell"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Paluvai, H., Di Giorgio, E., and Brancolini, C. (2020). The Histone Code of Senescence. Cells, 9.","DOI":"10.3390\/cells9020466"},{"key":"ref_103","unstructured":"Harrington, D.J. (2019). Laboratory Assessment of Vitamin Status, Elsevier."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1080\/10408363.2021.1885339","article-title":"Vitamin B12 Status in Health and Disease: A Critical Review. Diagnosis of Deficiency and Insufficiency\u2014Clinical and Laboratory Pitfalls","volume":"58","author":"Delvin","year":"2021","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_105","first-page":"1205","article-title":"Comparison of Four Automated Serum Vitamin B12 Assays","volume":"53","author":"Serdar","year":"2015","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1515\/CCLM.2008.356","article-title":"Accurate Assessment and Identification of Naturally Occurring Cellular Cobalamins","volume":"46","author":"Hannibal","year":"2008","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"17040","DOI":"10.1038\/nrdp.2017.40","article-title":"Vitamin B12 Deficiency","volume":"3","author":"Green","year":"2017","journal-title":"Nat. Rev. Dis. Primer"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Kulkarni, A., Dangat, K., Kale, A., Sable, P., Chavan-Gautam, P., and Joshi, S. (2011). Effects of Altered Maternal Folic Acid, Vitamin B12 and Docosahexaenoic Acid on Placental Global DNA Methylation Patterns in Wistar Rats. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017706"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Kumar, K.A., Lalitha, A., Reddy, U., Chandak, G.R., Sengupta, S., and Raghunath, M. (2014). Chronic Maternal Vitamin B12 Restriction Induced Changes in Body Composition & Glucose Metabolism in the Wistar Rat Offspring Are Partly Correctable by Rehabilitation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112991"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s11010-020-03713-x","article-title":"Maternal Vitamin B12 Deficiency in Rats Alters DNA Methylation in Metabolically Important Genes in Their Offspring","volume":"468","author":"Tanwar","year":"2020","journal-title":"Mol. Cell. Biochem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"19351","DOI":"10.1073\/pnas.0707258104","article-title":"DNA Methylation, Insulin Resistance, and Blood Pressure in Offspring Determined by Maternal Periconceptional B Vitamin and Methionine Status","volume":"104","author":"Sinclair","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Sharma, G.S., Kumar, T., and Singh, L.R. (2014). N-Homocysteinylation Induces Different Structural and Functional Consequences on Acidic and Basic Proteins. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0116386"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"3436","DOI":"10.1038\/s41467-018-05451-7","article-title":"Elevated H3K79 Homocysteinylation Causes Abnormal Gene Expression during Neural Development and Subsequent Neural Tube Defects","volume":"9","author":"Zhang","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1080\/1028415X.2018.1548676","article-title":"Increased Stress and Altered Expression of Histone Modifying Enzymes in Brain Are Associated with Aberrant Behaviour in Vitamin B12 Deficient Female Mice","volume":"23","author":"Ghosh","year":"2020","journal-title":"Nutr. Neurosci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"15078","DOI":"10.1021\/ja904670x","article-title":"Vitamin B12 and Redox Homeostasis: Cob(II)Alamin Reacts with Superoxide at Rates Approaching Superoxide Dismutase (SOD)","volume":"131","author":"Yun","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Li, F., Bahnson, E.M., Wilder, J., Siletzky, R., Hagaman, J., Nickekeit, V., Hiller, S., Ayesha, A., Feng, L., and Levine, J.S. (2020). Oral High Dose Vitamin B12 Decreases Renal Superoxide and Post-Ischemia\/Reperfusion Injury in Mice. Redox Biol., 32.","DOI":"10.1016\/j.redox.2020.101504"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1007\/s10545-008-0839-4","article-title":"Causes of and Diagnostic Approach to Methylmalonic Acidurias","volume":"31","author":"Fowler","year":"2008","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ymgme.2016.07.013","article-title":"Ammonium Accumulation Is a Primary Effect of 2-Methylcitrate Exposure in an in Vitro Model for Brain Damage in Methylmalonic Aciduria","volume":"119","author":"Zavadakova","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/2464","article-title":"Abnormal Maternal Behaviour and Growth Retardation Associated with Loss of the Imprinted Gene Mest","volume":"20","author":"Lefebvre","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Sapehia, D., Mahajan, A., Singh, P., and Kaur, J. (2023). High Dietary Folate and Low Vitamin B12 in Parental Diet Disturbs the Epigenetics of Imprinted Genes MEST and PHLDA2 in Mice Placenta. J. Nutr. Biochem., 118.","DOI":"10.1016\/j.jnutbio.2023.109354"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s12974-020-01763-y","article-title":"Vitamin B12 Is Neuroprotective in Experimental Pneumococcal Meningitis through Modulation of Hippocampal DNA Methylation","volume":"17","author":"Lopes","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1093\/nutrit\/nuab092","article-title":"The Role of Vitamin B12 in Viral Infections: A Comprehensive Review of Its Relationship with the Muscle\u2013Gut\u2013Brain Axis and Implications for SARS-CoV-2 Infection","volume":"80","author":"Batista","year":"2022","journal-title":"Nutr. Rev."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/s12031-013-9996-5","article-title":"Neuroprotective Effects of NMDA and Group I Metabotropic Glutamate Receptor Antagonists Against Neurodegeneration Induced by Homocysteine in Rat Hippocampus: In Vivo Study","volume":"50","author":"Yeganeh","year":"2013","journal-title":"J. Mol. Neurosci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"32","DOI":"10.22540\/JFSF-07-032","article-title":"B12 Levels and Frailty Syndrome","volume":"7","author":"Pyrgioti","year":"2022","journal-title":"J. Frailty Sarcopenia Falls"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.neurobiolaging.2007.07.020","article-title":"DNA Methylation Impacts on Learning and Memory in Aging","volume":"30","author":"Liu","year":"2009","journal-title":"Neurobiol. Aging"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1038\/nn.3151","article-title":"Rescue of Aging-Associated Decline in Dnmt3a2 Expression Restores Cognitive Abilities","volume":"15","author":"Oliveira","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"4830","DOI":"10.1073\/pnas.1524857113","article-title":"Stress-Induced Gene Expression and Behavior Are Controlled by DNA Methylation and Methyl Donor Availability in the Dentate Gyrus","volume":"113","author":"Saunderson","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_128","unstructured":"Loenen, W.A. (2018). Epigenetics of Aging and Longevity, Elsevier."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"777","DOI":"10.3233\/JAD-150140","article-title":"Associations between Homocysteine, Folic Acid, Vitamin B12 and Alzheimer\u2019s Disease: Insights from Meta-Analyses","volume":"46","author":"Shen","year":"2015","journal-title":"J. Alzheimers Dis."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.mayocp.2019.01.039","article-title":"Low Vitamin B12 and Parkinson Disease","volume":"94","author":"McCarter","year":"2019","journal-title":"Mayo Clin. Proc."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1093\/qjmed\/hct051","article-title":"The Pathophysiology of Elevated Vitamin B12 in Clinical Practice","volume":"106","author":"Serraj","year":"2013","journal-title":"QJM Int. J. Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1179\/1476830515Y.0000000041","article-title":"Novel Relationships between B12, Folate and Markers of Inflammation, Oxidative Stress and NAD(H) Levels, Systemically and in the CNS of a Healthy Human Cohort","volume":"18","author":"Guest","year":"2015","journal-title":"Nutr. Neurosci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The Hallmarks of Aging","volume":"153","author":"Blasco","year":"2013","journal-title":"Cell"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1134\/S000629792402010X","article-title":"AgeMeta: Quantitative Gene Expression Database of Mammalian Aging","volume":"89","author":"Tikhonov","year":"2024","journal-title":"Biochem. Mosc."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.2147\/TCRM.S164200","article-title":"Elevated Levels of Vitamin B12 in Chronic Stable Heart Failure: A Marker for Subclinical Liver Damage and Impaired Prognosis","volume":"14","author":"Argan","year":"2018","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1093\/gerona\/gly035","article-title":"Elevated Total Homocysteine in All Participants and Plasma Vitamin B12 Concentrations in Women Are Associated With All-Cause and Cardiovascular Mortality in the Very Old: The Newcastle 85+ Study","volume":"73","author":"Jagger","year":"2018","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.clnu.2011.08.010","article-title":"Increased Vitamin B12 Levels Are Associated with Mortality in Critically Ill Medical Patients","volume":"31","author":"Sviri","year":"2012","journal-title":"Clin. Nutr."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"e13338","DOI":"10.1111\/acel.13338","article-title":"Cellular Aging beyond Cellular Senescence: Markers of Senescence Prior to Cell Cycle Arrest in Vitro and in Vivo","volume":"20","author":"Ogrodnik","year":"2021","journal-title":"Aging Cell"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Liu, J., Wang, L., Wang, Z., and Liu, J.-P. (2019). Roles of Telomere Biology in Cell Senescence, Replicative and Chronological Ageing. Cells, 8.","DOI":"10.3390\/cells8010054"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.cell.2019.10.005","article-title":"Cellular Senescence: Defining a Path Forward","volume":"179","author":"Gorgoulis","year":"2019","journal-title":"Cell"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/s41588-023-01627-0","article-title":"Distinguishing between Driver and Passenger Mechanisms of Aging","volume":"56","year":"2024","journal-title":"Nat. Genet."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1038\/nprot.2009.191","article-title":"Protocols to Detect Senescence-Associated Beta-Galactosidase (SA-\u0392gal) Activity, a Biomarker of Senescent Cells in Culture and in Vivo","volume":"4","author":"Erusalimsky","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.1474-9726.2006.00199.x","article-title":"Senescence-Associated \u03b2-Galactosidase Is Lysosomal \u03b2-Galactosidase","volume":"5","author":"Lee","year":"2006","journal-title":"Aging Cell"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/368753a0","article-title":"Deletions of the Cyclin-Dependent Kinase-4 Inhibitor Gene in Multiple Human Cancers","volume":"368","author":"Nobori","year":"1994","journal-title":"Nature"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1111\/j.1474-9726.2009.00489.x","article-title":"Expression of P16  INK4a  in Peripheral Blood T-cells Is a Biomarker of Human Aging","volume":"8","author":"Liu","year":"2009","journal-title":"Aging Cell"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.bbrc.2014.08.123","article-title":"Reactive Oxygen Species Promotes Cellular Senescence in Normal Human Epidermal Keratinocytes through Epigenetic Regulation of P16INK4a","volume":"452","author":"Sasaki","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1097\/CCO.0b013e32835b639e","article-title":"P21WAF1 and Tumourigenesis: 20 Years After","volume":"25","author":"Warfel","year":"2013","journal-title":"Curr. Opin. Oncol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1007\/s11357-023-00929-9","article-title":"Bleomycin-Treated Myoblasts Undergo P21-Associated Cellular Senescence and Have Severely Impaired Differentiation","volume":"46","author":"Kamal","year":"2023","journal-title":"GeroScience"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1128\/MCB.19.3.2109","article-title":"Differential Roles for Cyclin-Dependent Kinase Inhibitors P21 and P16 in the Mechanisms of Senescence and Differentiation in Human Fibroblasts","volume":"19","author":"Stein","year":"1999","journal-title":"Mol. Cell. Biol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/S0344-0338(96)80088-4","article-title":"The Role of P53 in Cell Cycle Regulation","volume":"192","author":"Shaw","year":"1996","journal-title":"Pathol.-Res. Pract."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"3722","DOI":"10.1038\/s41467-022-31239-x","article-title":"Senescent Cells Limit P53 Activity via Multiple Mechanisms to Remain Viable","volume":"13","author":"Sturmlechner","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"4212","DOI":"10.1093\/emboj\/cdg417","article-title":"Reversal of Human Cellular Senescence: Roles of the P53 and P16 Pathways","volume":"22","author":"Beausejour","year":"2003","journal-title":"EMBO J."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1146\/annurev-pathol-121808-102144","article-title":"The Senescence-Associated Secretory Phenotype: The Dark Side of Tumor Suppression","volume":"5","author":"Desprez","year":"2010","journal-title":"Annu. Rev. Pathol."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Cuollo, L., Antonangeli, F., Santoni, A., and Soriani, A. (2020). The Senescence-Associated Secretory Phenotype (SASP) in the Challenging Future of Cancer Therapy and Age-Related Diseases. Biology, 9.","DOI":"10.3390\/biology9120485"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.bbi.2022.05.016","article-title":"Stress-Induced Biological Aging: A Review and Guide for Research Priorities","volume":"104","author":"Polsky","year":"2022","journal-title":"Brain. Behav. Immun."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nature10599","article-title":"Senescence Surveillance of Pre-Malignant Hepatocytes Limits Liver Cancer Development","volume":"479","author":"Kang","year":"2011","journal-title":"Nature"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1016\/j.cell.2008.03.038","article-title":"Chemokine Signaling via the CXCR2 Receptor Reinforces Senescence","volume":"133","author":"Acosta","year":"2008","journal-title":"Cell"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.ccr.2013.06.005","article-title":"A Senescence-Inflammatory Switch from Cancer-Inhibitory to Cancer-Promoting Mechanism","volume":"24","author":"Pribluda","year":"2013","journal-title":"Cancer Cell"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.ccell.2016.09.003","article-title":"Distinct Functions of Senescence-Associated Immune Responses in Liver Tumor Surveillance and Tumor Progression","volume":"30","author":"Eggert","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"3148","DOI":"10.1038\/onc.2011.485","article-title":"SASP Mediates Chemoresistance and Tumor-Initiating-Activity of Mesothelioma Cells","volume":"31","author":"Canino","year":"2012","journal-title":"Oncogene"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s12307-011-0069-4","article-title":"Epithelial-Mesenchymal Transition Induced by Senescent Fibroblasts","volume":"5","author":"Laberge","year":"2012","journal-title":"Cancer Microenviron."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/nature25167","article-title":"Senescence-Associated Reprogramming Promotes Cancer Stemness","volume":"553","author":"Milanovic","year":"2018","journal-title":"Nature"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1158\/0008-5472.CAN-19-2830","article-title":"NAMPT Inhibition Suppresses Cancer Stem-like Cells Associated with Therapy-Induced Senescence in Ovarian Cancer","volume":"80","author":"Nacarelli","year":"2020","journal-title":"Cancer Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"15208","DOI":"10.1038\/ncomms15208","article-title":"Senescent Tumor Cells Lead the Collective Invasion in Thyroid Cancer","volume":"8","author":"Kim","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"29568","DOI":"10.1074\/jbc.M603307200","article-title":"Secretion of Vascular Endothelial Growth Factor by Primary Human Fibroblasts at Senescence","volume":"281","author":"Kauser","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1158\/1541-7786.MCR-15-0348","article-title":"Chemotherapy-Induced Inflammatory Gene Signature and Protumorigenic Phenotype in Pancreatic CAFs via Stress-Associated MAPK","volume":"14","author":"Toste","year":"2016","journal-title":"Mol. Cancer Res."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"11762","DOI":"10.1038\/ncomms11762","article-title":"Stromal Senescence Establishes an Immunosuppressive Microenvironment That Drives Tumorigenesis","volume":"7","author":"Ruhland","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1158\/0008-5472.CAN-12-2301","article-title":"Constitutive HER2 Signaling Promotes Breast Cancer Metastasis through Cellular Senescence","volume":"73","author":"Angelini","year":"2013","journal-title":"Cancer Res."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1158\/2159-8290.CD-16-0241","article-title":"Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse","volume":"7","author":"Demaria","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.ccell.2018.06.007","article-title":"PTBP1-Mediated Alternative Splicing Regulates the Inflammatory Secretome and the Pro-Tumorigenic Effects of Senescent Cells","volume":"34","author":"Georgilis","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.ccr.2012.04.027","article-title":"P53-Mediated Senescence Impairs the Apoptotic Response to Chemotherapy and Clinical Outcome in Breast Cancer","volume":"21","author":"Jackson","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1038\/nm.2890","article-title":"Treatment-Induced Damage to the Tumor Microenvironment Promotes Prostate Cancer Therapy Resistance through WNT16B","volume":"18","author":"Sun","year":"2012","journal-title":"Nat. Med."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1111\/febs.16381","article-title":"The Role of Cellular Senescence and SASP in Tumour Microenvironment","volume":"290","author":"Takasugi","year":"2023","journal-title":"FEBS J."},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Carpenter, V.J., Saleh, T., and Gewirtz, D.A. (2021). Senolytics for Cancer Therapy: Is All That Glitters Really Gold?. Cancers, 13.","DOI":"10.3390\/cancers13040723"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/s43587-023-00365-6","article-title":"Senescent Cells, Senolytics and Tissue Repair: The Devil May Be in the Dosing","volume":"3","author":"Khosla","year":"2023","journal-title":"Nat. Aging"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1101\/gad.173922.111","article-title":"Rejuvenating Senescent and Centenarian Human Cells by Reprogramming through the Pluripotent State","volume":"25","author":"Lapasset","year":"2011","journal-title":"Genes Dev."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1038\/s41556-023-01214-9","article-title":"P16High Senescence Restricts Cellular Plasticity during Somatic Cell Reprogramming","volume":"25","author":"Grigorash","year":"2023","journal-title":"Nat. Cell Biol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1038\/s42255-023-00916-6","article-title":"Vitamin B12 Is a Limiting Factor for Induced Cellular Plasticity and Tissue Repair","volume":"5","author":"Kovatcheva","year":"2023","journal-title":"Nat. Metab."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/S0092-8674(03)00401-X","article-title":"Rb-Mediated Heterochromatin Formation and Silencing of E2F Target Genes during Cellular Senescence","volume":"113","author":"Narita","year":"2003","journal-title":"Cell"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.molcel.2012.06.010","article-title":"Independence of Repressive Histone Marks and Chromatin Compaction during Senescent Heterochromatic Layer Formation","volume":"47","author":"Chandra","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"23","DOI":"10.4161\/nucl.23189","article-title":"High-Order Chromatin Structure and the Epigenome in SAHFs","volume":"4","author":"Chandra","year":"2013","journal-title":"Nucleus"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1017\/S0029665111003302","article-title":"Nutritional Influences on Epigenetics and Age-Related Disease","volume":"71","author":"Park","year":"2012","journal-title":"Proc. Nutr. Soc."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/ncb2170","article-title":"Interplay between Oncogene-Induced DNA Damage Response and Heterochromatin in Senescence and Cancer","volume":"13","author":"Sulli","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"138","DOI":"10.3389\/fgene.2017.00138","article-title":"Epigenetic Regulation of Cellular Senescence and Aging","volume":"8","author":"Sidler","year":"2017","journal-title":"Front. Genet."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"39195","DOI":"10.1074\/jbc.M205166200","article-title":"Postsynthetic Trimethylation of Histone H4 at Lysine 20 in Mammalian Tissues Is Associated with Aging","volume":"277","author":"Sarg","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_187","doi-asserted-by":"crossref","unstructured":"Ramponi, V., Richart, L., Kovatcheva, M., Stephan-Otto Attolini, C., Capellades, J., Lord, A.E., Yanes, O., Ficz, G., and Serrano, M. (2024). Persister Cancer Cells Are Characterized by H4K20me3 Heterochromatin That Defines a Low Inflammatory Profile. bioRxiv.","DOI":"10.1101\/2024.01.26.577389"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1038\/ncomms2885","article-title":"Depleting the Methyltransferase Suv39h1 Improves DNA Repair and Extends Lifespan in a Progeria Mouse Model","volume":"4","author":"Liu","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/nm1204","article-title":"Reversal of the Cellular Phenotype in the Premature Aging Disease Hutchinson-Gilford Progeria Syndrome","volume":"11","author":"Scaffidi","year":"2005","journal-title":"Nat. Med."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"8703","DOI":"10.1073\/pnas.0602569103","article-title":"Mutant Nuclear Lamin A Leads to Progressive Alterations of Epigenetic Control in Premature Aging","volume":"103","author":"Shumaker","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"7083","DOI":"10.18632\/aging.102238","article-title":"Telomere Length, Vitamin B12 and Mortality in Persons Undergoing Coronary Angiography: The Ludwigshafen Risk and Cardiovascular Health Study","volume":"11","author":"Pusceddu","year":"2019","journal-title":"Aging"},{"key":"ref_192","doi-asserted-by":"crossref","unstructured":"Xin, H., Liu, D., and Songyang, Z. (2008). The Telosome\/Shelterin Complex and Its Functions. Genome Biol., 9.","DOI":"10.1186\/gb-2008-9-9-232"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.3945\/ajcn.2008.26986","article-title":"Multivitamin Use and Telomere Length in Women","volume":"89","author":"Xu","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3945\/an.111.000992","article-title":"Folate and DNA Methylation: A Review of Molecular Mechanisms and the Evidence for Folate\u2019s Role","volume":"3","author":"Crider","year":"2012","journal-title":"Adv. Nutr."},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"Rzepka, Z., Rok, J., Kowalska, J., Banach, K., and Wrze\u015bniok, D. (2022). Cobalamin Deficiency May Induce Astrosenescence\u2014An In Vitro Study. Cells, 11.","DOI":"10.3390\/cells11213408"},{"key":"ref_196","first-page":"1829","article-title":"P53 and P21 Expression in Bone Marrow Clots of Megaloblastic Anemia Patients","volume":"13","author":"Kwan","year":"2020","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.nupar.2021.07.002","article-title":"Restrictions and Supplementations Effects of Vitamins B6, B9 and B12 on Growth, Vasculogenesis and Senescence of BG01V Human Embryonic Stem Cell Derived Embryoid Bodies","volume":"35","author":"Bhanothu","year":"2021","journal-title":"Nutr. Clin. M\u00e9tab."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/bs.vh.2022.01.014","article-title":"Chapter Eleven\u2014Telomere Length and Vitamin B12","volume":"Volume 119","author":"Litwack","year":"2022","journal-title":"Vitamins and Hormones"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"106193","DOI":"10.1016\/j.isci.2023.106193","article-title":"Histone Malonylation Is Regulated by SIRT5 and KAT2A","volume":"26","author":"Zhang","year":"2023","journal-title":"iScience"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"e553","DOI":"10.1038\/cddis.2013.69","article-title":"Decreased Vitamin B12 Availability Induces ER Stress through Impaired SIRT1-Deacetylation of HSF1","volume":"4","author":"Ghemrawi","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"657","DOI":"10.3389\/fendo.2018.00657","article-title":"Metformin Is a Direct SIRT1-Activating Compound: Computational Modeling and Experimental Validation","volume":"9","author":"Verdura","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1126\/science.289.5487.2126","article-title":"Requirement of NAD and SIR2 for Life-Span Extension by Calorie Restriction in Saccharomyces cerevisiae","volume":"289","author":"Lin","year":"2000","journal-title":"Science"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41586-020-2630-0","article-title":"Age-Induced Accumulation of Methylmalonic Acid Promotes Tumour Progression","volume":"585","author":"Gomes","year":"2020","journal-title":"Nature"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"101743","DOI":"10.1016\/j.arr.2022.101743","article-title":"Epigenetic Clock: A Promising Biomarker and Practical Tool in Aging","volume":"81","author":"Duan","year":"2022","journal-title":"Ageing Res. Rev."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.cell.2022.12.027","article-title":"Loss of Epigenetic Information as a Cause of Mammalian Aging","volume":"186","author":"Yang","year":"2023","journal-title":"Cell"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s43587-023-00384-3","article-title":"Spurious Intragenic Transcription Is a Feature of Mammalian Cellular Senescence and Tissue Aging","volume":"3","author":"Sen","year":"2023","journal-title":"Nat. Aging"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1159\/000211967","article-title":"The 5-Methylcytosine in DNA of Rats","volume":"19","author":"Vanyushin","year":"1973","journal-title":"Gerontology"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"9948","DOI":"10.1016\/S0021-9258(18)61057-9","article-title":"Genomic 5-Methyldeoxycytidine Decreases with Age","volume":"262","author":"Wilson","year":"1987","journal-title":"J. Biol. Chem."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/0921-8734(89)90038-6","article-title":"Human Lymphocytes Aged in Vivo Have Reduced Levels of Methylation in Transcriptionally Active and Inactive DNA","volume":"219","author":"Drinkwater","year":"1989","journal-title":"Mutat. Res."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1743-7075-9-41","article-title":"Vitamin B12 Deficiency in the Brain Leads to DNA Hypomethylation in the TCblR\/CD320 Knockout Mouse","volume":"9","author":"Lai","year":"2012","journal-title":"Nutr. Metab."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1093\/nutrit\/nuz094","article-title":"Influence of Nutrients Involved in One-Carbon Metabolism on DNA Methylation in Adults\u2014A Systematic Review and Meta-Analysis","volume":"78","author":"Amenyah","year":"2020","journal-title":"Nutr. Rev."},{"key":"ref_212","doi-asserted-by":"crossref","unstructured":"Weidner, C.I., Lin, Q., Koch, C.M., Eisele, L., Beier, F., Ziegler, P., Bauerschlag, D.O., J\u00f6ckel, K.H., Erbel, R., and M\u00fchleisen, T.W. (2014). Aging of Blood Can Be Tracked by DNA Methylation Changes at Just Three CpG Sites. Genome Biol., 15.","DOI":"10.1186\/gb-2014-15-2-r24"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.numecd.2017.12.006","article-title":"Effect of Adding B-Vitamins to Vitamin D and Calcium Supplementation on CpG Methylation of Epigenetic Aging Markers","volume":"28","author":"Obeid","year":"2018","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"1800092","DOI":"10.1002\/mnfr.201800092","article-title":"Dietary Intervention Modifies DNA Methylation Age Assessed by the Epigenetic Clock","volume":"62","author":"Corsi","year":"2018","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"2718","DOI":"10.1016\/j.devcel.2023.08.019","article-title":"Mitochondrial GTP Metabolism Controls Reproductive Aging in C. Elegans","volume":"58","author":"Lee","year":"2023","journal-title":"Dev. Cell"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s13148-021-01065-x","article-title":"Associations of Circulating Folate, Vitamin B12 and Homocysteine Concentrations in Early Pregnancy and Cord Blood with Epigenetic Gestational Age: The Generation R Study","volume":"13","author":"Monasso","year":"2021","journal-title":"Clin. Epigenet."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"3820","DOI":"10.1038\/s41467-020-17636-0","article-title":"Associations of Cardiovascular Biomarkers and Plasma Albumin with Exceptional Survival to the Highest Ages","volume":"11","author":"Hirata","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_218","doi-asserted-by":"crossref","unstructured":"Bogdanova, D.A., Kolosova, E.D., Pukhalskaia, T.V., Levchuk, K.A., Demidov, O.N., and Belotserkovskaya, E.V. (2024). The Differential Effect of Senolytics on SASP Cytokine Secretion and Regulation of EMT by CAFs. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25074031"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s12964-017-0172-3","article-title":"Senescence-Associated IL-6 and IL-8 Cytokines Induce a Self- and Cross-Reinforced Senescence\/Inflammatory Milieu Strengthening Tumorigenic Capabilities in the MCF-7 Breast Cancer Cell Line","volume":"15","author":"Vernot","year":"2017","journal-title":"Cell Commun. Signal."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"e008517","DOI":"10.1161\/JAHA.117.008517","article-title":"Effect of Combined Treatment With Folic Acid, Vitamin B 6, and Vitamin B12 on Plasma Biomarkers of Inflammation and Endothelial Dysfunction in Women","volume":"7","author":"Christen","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1080\/10520290701791839","article-title":"The Return of the Scarlet Pimpernel: Cobalamin in Inflammation II\u2014Cobalamins Can Both Selectively Promote All Three Nitric Oxide Synthases (NOS), Particularly INOS and ENOS, and, as Needed, Selectively Inhibit INOS and NNOS","volume":"16","author":"Wheatley","year":"2007","journal-title":"J. Nutr. Environ. Med."},{"key":"ref_222","doi-asserted-by":"crossref","unstructured":"Lee, Y.-J., Wang, M.-Y., Lin, M.-C., and Lin, P.-T. (2016). Associations between Vitamin B-12 Status and Oxidative Stress and Inflammation in Diabetic Vegetarians and Omnivores. Nutrients, 8.","DOI":"10.3390\/nu8030118"},{"key":"ref_223","doi-asserted-by":"crossref","unstructured":"Gubernatorova, E.O., Polinova, A.I., Petropavlovskiy, M.M., Namakanova, O.A., Medvedovskaya, A.D., Zvartsev, R.V., Telegin, G.B., Drutskaya, M.S., and Nedospasov, S.A. (2021). Dual Role of TNF and LT\u03b1 in Carcinogenesis as Implicated by Studies in Mice. Cancers, 13.","DOI":"10.3390\/cancers13081775"},{"key":"ref_224","first-page":"441","article-title":"Transcobalamin II","volume":"12","author":"Rothenberg","year":"1999","journal-title":"Chem. Biochem. Vitam. B"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1002\/ana.20325","article-title":"High Tumor Necrosis Factor-\u03b1 in Levels in Cerebrospinal Fluid of Cobalamin-deficient Patients","volume":"56","author":"Scalabrino","year":"2004","journal-title":"Ann. Neurol."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.abb.2007.03.011","article-title":"Cobalamin-Mediated Regulation of Transcobalamin Receptor Levels in Rat Organs","volume":"463","author":"Kalra","year":"2007","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1002\/jnr.21599","article-title":"Indirect Down-regulation of Nuclear NF-\u03baB Levels by Cobalamin in the Spinal Cord and Liver of the Rat","volume":"86","author":"Veber","year":"2008","journal-title":"J. Neurosci. Res."},{"key":"ref_228","doi-asserted-by":"crossref","unstructured":"Homann, L., Rentschler, M., Brenner, E., B\u00f6hm, K., R\u00f6cken, M., and Wieder, T. (2022). IFN-\u03b3 and TNF Induce Senescence and a Distinct Senescence-Associated Secretory Phenotype in Melanoma. Cells, 11.","DOI":"10.3390\/cells11091514"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"e13646","DOI":"10.1111\/acel.13646","article-title":"TNF -\u03b1\/ IFN -\u03b3 Synergy Amplifies Senescence-associated Inflammation and SARS-CoV -2 Receptor Expression via Hyper-activated JAK \/ STAT1","volume":"21","author":"Yang","year":"2022","journal-title":"Aging Cell"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"7820","DOI":"10.1073\/pnas.1218599110","article-title":"Immune-Responsive Gene 1 Protein Links Metabolism to Immunity by Catalyzing Itaconic Acid Production","volume":"110","author":"Michelucci","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.cell.2017.09.051","article-title":"The Human Knockout Gene CLYBL Connects Itaconate to Vitamin B12","volume":"171","author":"Shen","year":"2017","journal-title":"Cell"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1126\/science.aay0934","article-title":"Itaconyl-CoA Forms a Stable Biradical in Methylmalonyl-CoA Mutase and Derails Its Activity and Repair","volume":"366","author":"Ruetz","year":"2019","journal-title":"Science"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/j.1749-6632.2000.tb06651.x","article-title":"Inflamm-aging: An Evolutionary Perspective on Immunosenescence","volume":"908","author":"Franceschi","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"885879","DOI":"10.3389\/fendo.2022.885879","article-title":"Aging Relevant Metabolite Itaconate Inhibits Inflammatory Bone Loss","volume":"13","author":"Wang","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_235","doi-asserted-by":"crossref","unstructured":"Martucci, M., Conte, M., Bucci, L., Giampieri, E., Fabbri, C., Palmas, M., Izzi, M., Salvioli, S., Zambrini, A., and Orsi, C. (2020). Twelve-Week Daily Consumption of Ad Hoc Fortified Milk with \u03c9-3, D, and Group B Vitamins Has a Positive Impact on Inflammaging Parameters: A Randomized Cross-Over Trial. Nutrients, 12.","DOI":"10.3390\/nu12113580"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1038\/s43587-022-00306-9","article-title":"Toward an Improved Definition of a Healthy Microbiome for Healthy Aging","volume":"2","author":"Ghosh","year":"2022","journal-title":"Nat. Aging"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/nature11319","article-title":"Gut Microbiota Composition Correlates with Diet and Health in the Elderly","volume":"488","author":"Claesson","year":"2012","journal-title":"Nature"},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"2025016","DOI":"10.1080\/19490976.2021.2025016","article-title":"Human Gut Microbiome Aging Clocks Based on Taxonomic and Functional Signatures through Multi-View Learning","volume":"14","author":"Chen","year":"2022","journal-title":"Gut Microbes"},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.0954-6820.1968.tb02452.x","article-title":"Oral treatment of pernicious anemia with high doses of vitamin b12 without intrinsic factor","volume":"184","author":"Berlin","year":"1968","journal-title":"Acta Med. Scand."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1182\/blood.V92.4.1191","article-title":"Effective Treatment of Cobalamin Deficiency With Oral Cobalamin","volume":"92","author":"Kuzminski","year":"1998","journal-title":"Blood"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1146\/annurev.nu.02.070182.002015","article-title":"Absorption and Transport of Cobalamin (Vitamin B12)","volume":"2","author":"Seetharam","year":"1982","journal-title":"Annu. Rev. Nutr."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1093\/ajcn\/87.5.1324","article-title":"Identification and Quantitation of Cobalamin and Cobalamin Analogues in Human Feces","volume":"87","author":"Allen","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1038\/s41591-019-0504-5","article-title":"Healthspan and Lifespan Extension by Fecal Microbiota Transplantation into Progeroid Mice","volume":"25","author":"Mayoral","year":"2019","journal-title":"Nat. Med."},{"key":"ref_244","doi-asserted-by":"crossref","unstructured":"Parker, A., Romano, S., Ansorge, R., Aboelnour, A., Le Gall, G., Savva, G.M., Pontifex, M.G., Telatin, A., Baker, D., and Jones, E. (2022). Fecal Microbiota Transfer between Young and Aged Mice Reverses Hallmarks of the Aging Gut, Eye, and Brain. Microbiome, 10.","DOI":"10.1186\/s40168-022-01243-w"},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1016\/j.cub.2016.04.016","article-title":"Gut Microbiota and Extreme Longevity","volume":"26","author":"Biagi","year":"2016","journal-title":"Curr. Biol."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/s41586-021-03832-5","article-title":"Novel Bile Acid Biosynthetic Pathways Are Enriched in the Microbiome of Centenarians","volume":"599","author":"Sato","year":"2021","journal-title":"Nature"},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/s41556-023-01145-5","article-title":"Bacterial Induction of B Cell Senescence Promotes Age-Related Changes in the Gut Microbiota","volume":"25","author":"Kawamoto","year":"2023","journal-title":"Nat. Cell Biol."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cmet.2020.04.001","article-title":"Benefits of Metformin in Attenuating the Hallmarks of Aging","volume":"32","author":"Kulkarni","year":"2020","journal-title":"Cell Metab."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1038\/onc.2017.367","article-title":"Metformin Regulates Global DNA Methylation via Mitochondrial One-Carbon Metabolism","volume":"37","author":"Verdura","year":"2018","journal-title":"Oncogene"},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1210\/jc.2015-3754","article-title":"Long-Term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study","volume":"101","author":"Aroda","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1038\/s41467-023-36525-w","article-title":"Evolutionary Conservation of the Fidelity of Transcription","volume":"14","author":"Chung","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/s41586-023-05922-y","article-title":"Ageing-Associated Changes in Transcriptional Elongation Influence Longevity","volume":"616","author":"Papadakis","year":"2023","journal-title":"Nature"},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.snb.2017.11.030","article-title":"Live Cell Imaging of Vitamin B12 Dynamics by Genetically Encoded Fluorescent Nanosensor","volume":"257","author":"Ahmad","year":"2018","journal-title":"Sens. Actuators B Chem."},{"key":"ref_254","doi-asserted-by":"crossref","unstructured":"Soleja, N., Agrawal, N., Nazir, R., Ahmad, M., and Mohsin, M. (2020). Enhanced Sensitivity and Detection Range of FRET-Based Vitamin B12 Nanosensor. 3 Biotech, 10.","DOI":"10.1007\/s13205-020-2073-1"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/9\/5044\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:40:14Z","timestamp":1760107214000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/9\/5044"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,6]]},"references-count":254,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["ijms25095044"],"URL":"https:\/\/doi.org\/10.3390\/ijms25095044","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,6]]}}}