{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:24:11Z","timestamp":1792092251105,"version":"4.4.0"},"reference-count":132,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronological age is a poor indicator of interindividual differences in biological aging. DNA methylation-based epigenetic clocks provide a reliable measure of biological age and epigenetic age acceleration (EAA). Although modifiable behavioral, environmental, and social factors appear to influence EAA, the magnitude, consistency, and potential preventability of these associations have never been systematically quantified. We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. PubMed\/MEDLINE and Scopus were searched from inception to 7 April 2026 for English-language observational and interventional studies reporting quantitative associations between modifiable determinants and EAA measured using validated clocks (Horvath, PhenoAge, GrimAge, DunedinPACE). Effect sizes were harmonized into four analytical pools. Random-effects meta-analyses were performed using the DerSimonian\u2013Laird estimator, with pre-specified subgroup analyses by exposure category. Heterogeneity, publication bias, and robustness were thoroughly assessed. A novel Modifiable Epigenetic Aging Burden Index (MEAB-Index) was developed to quantify the cumulative preventable burden. Only studies conducted in adult populations (\u226518 years) were eligible. Eighty-three studies providing 118 distinct exposure\u2013clock associations were included. In the primary analysis (Pool A, n = 60), adverse modifiable exposures were associated with accelerated EAA (pooled \u03b2 = +0.310 years per unit exposure, 95% CI 0.255\u20130.366). The strongest associations were observed for metabolic and inflammatory markers (\u03b2 = +0.913) and environmental exposures (\u03b2 = +0.466). The MEAB-Index yielded a Cumulative Preventable Burden of +1.566 years (bootstrap 95% CI 1.011\u20132.123). Findings were robust across sensitivity analyses and remained directionally consistent in secondary pools (B\u2013D). This study provides the most comprehensive quantitative synthesis to date on the modifiability of epigenetic aging. Our findings demonstrate that EAA is meaningfully shaped by behavioral, environmental, and social determinants. The MEAB-Index introduces a novel framework for estimating the preventable burden of biological aging and for prioritizing interventions. Reducing key modifiable risk factors, particularly metabolic\/inflammatory and environmental exposures, could substantially slow biological aging at the population level and support the transition toward ageing-centered preventive strategies.<\/jats:p>","DOI":"10.3390\/ijms27115032","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:38:42Z","timestamp":1780411122000},"page":"5032","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Epigenetic Age Acceleration as a Modifiable Public Health Target: A Systematic Review and Meta-Analysis of Environmental, Behavioral, and Social Determinants with Development of the MEAB-Index"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3462-6151","authenticated-orcid":false,"given":"Silvana Mirella","family":"Aliberti","sequence":"first","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, 84081 Salerno, Italy"},{"name":"Division of Preventive Medicine, Dresden International University (DIU), 01067 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1370-3057","authenticated-orcid":false,"given":"Piergiorgio","family":"Marigliano","sequence":"additional","affiliation":[{"name":"Department of Economics, eCampus University, 22060 Como, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Capunzo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, 84081 Salerno, Italy"},{"name":"Complex Operational Unit of Health and Hygiene, University Hospital \u201cSan Giovanni di Dio e Ruggi d\u2019Aragona\u201d, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"ref_1","unstructured":"WPP, World Population Prospects, United Nations, Department of Economic and Social Affairs (2026, April 15). Population Division. Available online: https:\/\/population.un.org\/wpp\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/s43856-025-01222-w","article-title":"Synergistic and heterogeneous aging using composite phenotypes and multiple organ systems aging clocks","volume":"5","author":"Li","year":"2025","journal-title":"Commun. Med."},{"key":"ref_3","first-page":"3520","article-title":"Epigenetic Clocks: Beyond Biological Age, Using the Past to Predict the Present and Future","volume":"16","author":"Liang","year":"2024","journal-title":"Aging Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3156","DOI":"10.1186\/gb-2013-14-10-r115","article-title":"DNA methylation age of human tissues and cell types","volume":"14","author":"Horvath","year":"2013","journal-title":"Genome Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"573","DOI":"10.18632\/aging.101414","article-title":"An epigenetic biomarker of aging for lifespan and healthspan","volume":"10","author":"Levine","year":"2018","journal-title":"Aging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"303","DOI":"10.18632\/aging.101684","article-title":"DNA methylation GrimAge strongly predicts lifespan and healthspan","volume":"11","author":"Lu","year":"2019","journal-title":"Aging"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e73420","DOI":"10.7554\/eLife.73420","article-title":"DunedinPACE, a DNA methylation biomarker of the pace of aging","volume":"11","author":"Belsky","year":"2022","journal-title":"eLife"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s13148-019-0656-7","article-title":"The epigenetic clock as a predictor of disease and mortality risk: A systematic review and meta-analysis","volume":"11","author":"Fransquet","year":"2019","journal-title":"Clin. Epigenet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"101348","DOI":"10.1016\/j.arr.2021.101348","article-title":"A systematic review of biological, social and environmental factors associated with epigenetic clock acceleration","volume":"69","author":"Oblak","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"afae127","DOI":"10.1093\/ageing\/afae127","article-title":"Epigenetic age acceleration and the risk of frailty, and persistent activities of daily living (ADL) disability","volume":"53","author":"Phyo","year":"2024","journal-title":"Age Ageing"},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1093\/gerona\/glz099","article-title":"A Systematic Review and Meta-analysis of Environmental, Lifestyle, and Health Factors Associated with DNA Methylation Age","volume":"75","author":"Ryan","year":"2020","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"419","DOI":"10.18632\/aging.101168","article-title":"Epigenetic clock analysis of diet, exercise, education, and lifestyle factors","volume":"9","author":"Quach","year":"2017","journal-title":"Aging"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"39936","DOI":"10.1038\/srep39936","article-title":"Very Early Colorectal Anastomotic Leakage within 5 Post-operative Days: A More Severe Subtype Needs Relaparatomy","volume":"7","author":"Li","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1057\/s41599-024-02730-1","article-title":"Exploring socioeconomic similarity-inequality: A regional perspective","volume":"11","year":"2024","journal-title":"Humanit. Soc. Sci. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1038\/s41440-025-02470-y","article-title":"Accelerated epigenetic age in hypertension: A systematic review and meta-analysis","volume":"49","author":"Dollin","year":"2026","journal-title":"Hypertens. Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Aliberti, S.M., De Caro, F., Funk, R.H.W., Schiavo, L., Gonnella, J., Boccia, G., and Capunzo, M. (2022). Extreme Longevity: Analysis of the Direct or Indirect Influence of Environmental Factors on Old, Nonagenarians, and Centenarians in Cilento, Italy. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19031589"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Aliberti, S.M., Funk, R.H.W., Schiavo, L., Giudice, A., Ciaglia, E., Puca, A.A., Gonnella, J., and Capunzo, M. (2022). Clinical Status, Nutritional Behavior, and Lifestyle, and Determinants of Community Well-Being of Patients from the Perspective of Physicians: A Cross-Sectional Study of Young Older Adults, Nonagenarians, and Centenarians in Salerno and Province, Italy. Nutrients, 14.","DOI":"10.3390\/nu14173665"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Aliberti, S.M., Donato, A., Funk, R.H.W., and Capunzo, M. (2024). A Narrative Review Exploring the Similarities between Cilento and the Already Defined \u201cBlue Zones\u201d in Terms of Environment, Nutrition, and Lifestyle: Can Cilento Be Considered an Undefined \u201cBlue Zone\u201d?. Nutrients, 16.","DOI":"10.3390\/nu16050729"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_21","unstructured":"NIHR. National Institute for Health and Care Research (2026, May 28). PROSPERO 2026 CRD420261371271, Available online: https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420261371271."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","article-title":"Meta-analysis in clinical trials","volume":"7","author":"DerSimonian","year":"1986","journal-title":"Control. Clin. Trials"},{"key":"ref_23","unstructured":"R Core Team (2024). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: https:\/\/www.R-project.org\/."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v036.i03","article-title":"Conducting meta-analyses in R with the metafor package","volume":"36","author":"Viechtbauer","year":"2010","journal-title":"J. Stat. Softw."},{"key":"ref_25","unstructured":"Python Software Foundation (2026, April 21). Python Language Reference, Available online: https:\/\/www.python.org\/."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s10522-025-10195-1","article-title":"Associations between lifestyle factors, physiological conditions, and epigenetic age acceleration in an Asian population","volume":"26","author":"Wu","year":"2025","journal-title":"Biogerontology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e2427889","DOI":"10.1001\/jamanetworkopen.2024.27889","article-title":"Sociodemographic and Lifestyle Factors and Epigenetic Aging in US Young Adults: NIMHD Social Epigenomics Program","volume":"7","author":"Harris","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4277","DOI":"10.1038\/s41598-022-08160-w","article-title":"Epigenome-wide association study and epigenetic age acceleration associated with cigarette smoking among Costa Rican adults","volume":"12","author":"Cardenas","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s13148-023-01480-2","article-title":"DNA methylation age at birth and childhood: Performance of epigenetic clocks and characteristics associated with epigenetic age acceleration in the Project Viva cohort","volume":"15","author":"Bozack","year":"2023","journal-title":"Clin. Epigenet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"eadl3747","DOI":"10.1126\/sciadv.adl3747","article-title":"Early-life exposure to tobacco, genetic susceptibility, and accelerated biological aging in adulthood","volume":"10","author":"Cui","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9350","DOI":"10.18632\/aging.205943","article-title":"Associations of childhood, adolescence, and midlife cognitive function with DNA methylation age acceleration in midlife","volume":"16","author":"Chen","year":"2024","journal-title":"Aging"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"116067","DOI":"10.1016\/j.envres.2023.116067","article-title":"Associations between prenatal phthalate exposure and childhood epigenetic age acceleration","volume":"231","author":"Khodasevich","year":"2023","journal-title":"Environ. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"L456","DOI":"10.1152\/ajplung.00171.2024","article-title":"Epigenetic age acceleration in idiopathic pulmonary fibrosis revealed by DNA methylation clocks","volume":"328","author":"Kurbanov","year":"2025","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12979-025-00500-4","article-title":"The relationship between biological aging and psoriasis: Evidence from three observational studies","volume":"22","author":"Lin","year":"2025","journal-title":"Immun. Ageing"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13148-025-01827-x","article-title":"Timing of menarche and menopause and epigenetic aging among U.S. adults: Results from the National Health and Nutrition Examination Survey 1999\u20132002","volume":"17","author":"Daredia","year":"2025","journal-title":"Clin. Epigenet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7752","DOI":"10.18632\/aging.204327","article-title":"Association between work characteristics and epigenetic age acceleration: Cross-sectional results from UK\u2014Understanding Society study","volume":"14","author":"Fiorito","year":"2022","journal-title":"Aging"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"108109","DOI":"10.1016\/j.envint.2023.108109","article-title":"Associations between medium- and long-term exposure to air temperature and epigenetic age acceleration","volume":"178","author":"Ni","year":"2023","journal-title":"Environ. Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"123371","DOI":"10.1016\/j.envres.2025.123371","article-title":"Occupational exposure to pesticides and epigenetic age acceleration in the Lifelines cohort study","volume":"289","author":"Zuo","year":"2026","journal-title":"Environ. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"108270","DOI":"10.1016\/j.envint.2023.108270","article-title":"Air pollution and epigenetic aging among Black and White women in the US","volume":"181","author":"Koenigsberg","year":"2023","journal-title":"Environ. Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"108041","DOI":"10.1016\/j.envint.2023.108041","article-title":"Household air pollution and epigenetic aging in Xuanwei, China","volume":"178","author":"Blechter","year":"2023","journal-title":"Environ. Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"107501","DOI":"10.1016\/j.envint.2022.107501","article-title":"Life-course exposure to air pollution and biological ageing in the Lothian Birth Cohort 1936","volume":"169","author":"Baranyi","year":"2022","journal-title":"Environ. Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"123284","DOI":"10.1016\/j.envres.2025.123284","article-title":"Long-term exposure to traffic-related air pollution is associated with epigenetic age acceleration","volume":"288","author":"Yao","year":"2026","journal-title":"Environ. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"114383","DOI":"10.1016\/j.isci.2025.114383","article-title":"Ambient temperature exposure on inflammatory blood proteins\u2014A longitudinal self-sampling survey in young Swedish adults","volume":"29","author":"Yu","year":"2025","journal-title":"iScience"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"105071","DOI":"10.1016\/j.envint.2019.105071","article-title":"Air pollution, particulate matter composition and methylation-based biologic age","volume":"132","author":"White","year":"2019","journal-title":"Environ. Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3558","DOI":"10.1038\/s41598-024-82747-3","article-title":"Greater residential greenness is associated with reduced epigenetic aging in adults","volume":"15","author":"Egorov","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e46152","DOI":"10.1097\/MD.0000000000046152","article-title":"Sex differences in the association between fatty liver index and biological aging: A mediation analysis of insulin resistance in a cross-sectional study","volume":"104","author":"Yang","year":"2025","journal-title":"Medicine"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Liu, N., Peng, S., Wei, K., Chen, Q., Chen, X., He, L., Wu, B., and Lin, Y. (2025). Association between cardiometabolic index and biological ageing among adults: A population-based study. BMC Public Health, 25.","DOI":"10.1186\/s12889-025-22053-3"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9987170","DOI":"10.1155\/mi\/9987170","article-title":"Association between neutrophil percentage\u2013albumin ratio and biological aging in rheumatoid arthritis in the United States: A cross-sectional study of NHANES","volume":"2026","author":"Xu","year":"2026","journal-title":"Mediat. Inflamm."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"113017","DOI":"10.1016\/j.exger.2025.113017","article-title":"Bidirectional associations between metabolic syndrome and epigenetic age acceleration: A 20-year longitudinal study in midlife adults","volume":"214","author":"Park","year":"2026","journal-title":"Exp. Gerontol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2541248","DOI":"10.1080\/15592294.2025.2541248","article-title":"Association of systemic immune-inflammation index (SII) with epigenetic age acceleration in adults: Insights from NHANES","volume":"20","author":"Liu","year":"2025","journal-title":"Epigenetics"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s41043-026-01255-4","article-title":"Epigenetic age and cardiometabolic disease in Guatemalan adults: A cross-sectional analysis","volume":"45","author":"Chapnick","year":"2026","journal-title":"J. Health Popul. Nutr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.18632\/aging.203872","article-title":"Work-related stress and well-being in association with epigenetic age acceleration: A Northern Finland Birth Cohort 1966 Study","volume":"14","author":"Fiorito","year":"2022","journal-title":"Aging"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1002\/da.23279","article-title":"Association between depression and epigenetic age acceleration: A co-twin control study","volume":"39","author":"Liu","year":"2022","journal-title":"Depress. Anxiety"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"glad118","DOI":"10.1093\/gerona\/glad118","article-title":"Association of Neighborhood Deprivation and Depressive Symptoms with Epigenetic Age Acceleration: Evidence from the Canadian Longitudinal Study on Aging","volume":"79","author":"Joshi","year":"2024","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1097\/PSY.0000000000001284","article-title":"Cumulative stress across the life course and biological aging in adulthood","volume":"86","author":"Suglia","year":"2024","journal-title":"Psychosom. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/jgs.18726","article-title":"Stressful life events, social support, and epigenetic aging in the Women\u2019s Health Initiative","volume":"72","author":"Skinner","year":"2024","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e13779","DOI":"10.1111\/acel.13779","article-title":"The association between adverse childhood experiences and epigenetic age acceleration in the Canadian longitudinal study on aging (CLSA)","volume":"22","author":"Joshi","year":"2023","journal-title":"Aging Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"gbae176","DOI":"10.1093\/geronb\/gbae176","article-title":"Neighborhood Stressors and Epigenetic Age Acceleration Among Older Americans","volume":"79","author":"Choi","year":"2024","journal-title":"J. Gerontol. Ser. B"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Ohi, K., Fujikane, D., Oida, Y., Takai, K., Ukisu, T., Nakahara, M., Murakami, H., Fujita, K., Kuramitsu, A., and Muto, Y. (2025). Epigenetic aging in anxiety disorders: Diagnostic subtype differences and associations with social functioning. BMC Med., 23.","DOI":"10.1186\/s12916-025-04480-6"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7883","DOI":"10.18632\/aging.202814","article-title":"Neighborhood environment, social cohesion, and epigenetic aging","volume":"13","author":"Martin","year":"2021","journal-title":"Aging"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Choi, B.Y., Ryo, S.W., Son, S.Y., Lee, J.H., Min, K.B., and Min, J.Y. (2025). Epigenetics-based age acceleration associated with 2,3,7,8 TCDD exposure in older Americans. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26041478"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"100778","DOI":"10.1016\/j.jnha.2026.100778","article-title":"Current marijuana use is cross-sectionally associated with accelerated biological aging among U.S. adults: Exploring mediating effect of blood cadmium","volume":"30","author":"Wei","year":"2026","journal-title":"J. Nutr. Health Aging"},{"key":"ref_63","first-page":"10938","article-title":"Alcohol consumption and epigenetic age acceleration across human adulthood","volume":"15","author":"Wang","year":"2023","journal-title":"Aging"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1093\/gerona\/glab149","article-title":"Alcohol Consumption and Methylation-Based Measures of Biological Age","volume":"76","author":"Kresovich","year":"2021","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Xia, T., Yuan, Q., Zhang, Y., and Shan, G. (2025). The associations between the energy and timing of sugar-sweetened beverage intake and phenotypic age acceleration in U.S. adults: A cross-sectional survey of NHANES 2007\u20132010. BMC Public Health, 25.","DOI":"10.1186\/s12889-024-21249-3"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1111\/acer.14528","article-title":"Associations of alcohol consumption with epigenome-wide DNA methylation and epigenetic age acceleration: Individual-level and co-twin comparison analyses","volume":"45","author":"Stephenson","year":"2021","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1007\/s40520-025-02964-2","article-title":"Systemic immune inflammation mediates the association of serum omega-3 and omega-6 polyunsaturated fatty acids with biological aging: A national population-based study","volume":"37","author":"Shan","year":"2025","journal-title":"Aging Clin. Exp. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41514-025-00306-0","article-title":"EAT-Lancet and plant-based diets, plasma metabolomic signatures, and biological aging","volume":"12","author":"Li","year":"2025","journal-title":"npj Aging"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41514-025-00298-x","article-title":"Dietary fatty acids and epigenetic aging in US adults: Results from the National Health and Nutrition Examination Survey","volume":"12","author":"Bozack","year":"2025","journal-title":"npj Aging"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"100776","DOI":"10.1016\/j.jnha.2026.100776","article-title":"Association between vitamin intake and biological aging: Evidence from NHANES 2007\u20132018","volume":"30","author":"Zhang","year":"2026","journal-title":"J. Nutr. Health Aging"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/s41538-025-00625-2","article-title":"Relationships among dietary patterns and heterogeneous biological aging at system and organ-specific levels and mortality risks","volume":"9","author":"Xu","year":"2025","journal-title":"npj Sci. Food"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1093\/aje\/kwaa251","article-title":"Associations of Body Composition and Physical Activity Level with Multiple Measures of Epigenetic Age Acceleration","volume":"190","author":"Kresovich","year":"2021","journal-title":"Am. J. Epidemiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e2421889","DOI":"10.1001\/jamanetworkopen.2024.21889","article-title":"Socioeconomic Status, Lifestyle, and DNA Methylation Age Among Racially and Ethnically Diverse Adults: NIMHD Social Epigenomics Program","volume":"7","author":"Maunakea","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e13828","DOI":"10.1111\/acel.13828","article-title":"Physical activity is associated with slower epigenetic ageing-Findings from the Rhineland study","volume":"22","author":"Fox","year":"2023","journal-title":"Aging Cell"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e13873","DOI":"10.1002\/jcsm.13873","article-title":"Physical Activity Is Associated with Decreased Epigenetic Aging: Findings from the Health and Retirement Study","volume":"16","author":"Ammous","year":"2025","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s13148-019-0613-5","article-title":"Leisure-time physical activity and DNA methylation age-a twin study","volume":"11","author":"Ollikainen","year":"2019","journal-title":"Clin. Epigenet."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s13148-024-01707-w","article-title":"Effects of walking on epigenetic age acceleration: A Mendelian randomization study","volume":"16","author":"Chen","year":"2024","journal-title":"Clin. Epigenet."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e70182","DOI":"10.1111\/acel.70182","article-title":"Epigenetic Age Monitoring in Professional Soccer Players for Tracking Recovery and the Effects of Strenuous Exercise","volume":"24","author":"Brooke","year":"2025","journal-title":"Aging Cell"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"22284","DOI":"10.1038\/s41598-022-26433-2","article-title":"Social mobility across the lifecourse and DNA methylation age acceleration in adults in the UK","volume":"12","author":"Bao","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e2024329","DOI":"10.1001\/jamanetworkopen.2020.24329","article-title":"Association of Neighborhood Deprivation with Epigenetic Aging Using 4 Clock Metrics","volume":"3","author":"Lawrence","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1038\/s41467-025-67622-7","article-title":"Social determinants of health, accelerated biological aging, and long-term health outcomes","volume":"17","author":"Li","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.annepidem.2023.10.003","article-title":"Maternal prenatal social experiences and offspring epigenetic age acceleration from birth to mid-childhood","volume":"90","author":"Laubach","year":"2024","journal-title":"Ann. Epidemiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s13148-024-01706-x","article-title":"The association between sleep quality and accelerated epigenetic aging with metabolic syndrome in Korean adults","volume":"16","author":"Lee","year":"2024","journal-title":"Clin. Epigenet."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.ebiom.2019.11.020","article-title":"Association between sleep disordered breathing and epigenetic age acceleration: Evidence from the Multi-Ethnic Study of Atherosclerosis","volume":"50","author":"Li","year":"2019","journal-title":"eBioMedicine"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s13148-025-01898-w","article-title":"Sleep patterns and DNA methylation age acceleration in middle-aged and older Chinese adults","volume":"17","author":"Diao","year":"2025","journal-title":"Clin. Epigenet."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41574-018-0059-4","article-title":"Inflammaging: A new immune\u2013metabolic viewpoint for age-related diseases","volume":"14","author":"Franceschi","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"102889","DOI":"10.1016\/j.jenvp.2025.102889","article-title":"Gardening, healthy aging, and longevity: Longitudinal evidence from 25 years of the Lothian Birth Cohort 1921","volume":"109","author":"Corley","year":"2026","journal-title":"J. Environ. Psychol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"107704","DOI":"10.1016\/j.psyneuen.2025.107704","article-title":"Aging anxiety and epigenetic aging in a national sample of adult women in the United States","volume":"184","author":"Rodrigues","year":"2026","journal-title":"Psychoneuroendocrinology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1007\/s11357-024-01408-5","article-title":"Physical activity and DNA methylation-based markers of ageing in 6208 middle-aged and older Australians: Cross-sectional and longitudinal analyses","volume":"47","author":"Zheng","year":"2025","journal-title":"GeroScience"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13148-024-01637-7","article-title":"Self-control is associated with health-relevant disparities in buccal DNA-methylation measures of biological aging in older adults","volume":"16","author":"Willems","year":"2024","journal-title":"Clin. Epigenet."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/s43587-024-00793-y","article-title":"Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial","volume":"5","author":"Wieczorek","year":"2025","journal-title":"Nat. Aging"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"gbaf194","DOI":"10.1093\/geronb\/gbaf194","article-title":"Social relationships and epigenetic markers of aging in middle-aged and older adults: Cross-sectional and prospective analyses","volume":"80","author":"Li","year":"2025","journal-title":"J. Gerontol. Ser. B"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1093\/gerona\/glad082","article-title":"Healthy Lifestyle Behaviors and Biological Aging in the U.S. National Health and Nutrition Examination Surveys 1999\u20132018","volume":"78","author":"Thomas","year":"2023","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Von Holle, A., Ramamurthy, S., D\u00edaz Santana, M.V., Kresovich, J.K., Taylor, J.A., Xu, Z., O\u2019Brien, K.M., Sandler, D.P., and Weinberg, C.R. (2025). Association Between Body Iron Status and Biological Aging. Nutrients, 17.","DOI":"10.3390\/nu17091409"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"41847","DOI":"10.1038\/s41598-025-25877-6","article-title":"Association of uric acid to high-density cholesterol ratio (UHR) with biological age acceleration: Evidence from NHANES 2009\u20132018","volume":"15","author":"Chen","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"123283","DOI":"10.1016\/j.envres.2025.123283","article-title":"Associations of paternal smoking exposure with newborn epigenetic age acceleration and telomere length","volume":"289","author":"Stagnar","year":"2026","journal-title":"Environ. Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"119562","DOI":"10.1016\/j.ecoenv.2025.119562","article-title":"The association of environmental toxicants exposure with cardiovascular disease risk: A comprehensive analysis from population to molecular mechanism","volume":"309","author":"Fang","year":"2026","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1186\/s12967-025-06492-5","article-title":"Early-life smoking, cardiovascular disease risk, and the mediating role of DNA methylation biomarkers of aging","volume":"23","author":"Sheng","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"7439","DOI":"10.1038\/s41598-024-84957-1","article-title":"Sleep traits causally affect epigenetic age acceleration: A Mendelian randomization study","volume":"15","author":"Zhao","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Hui, S., Hou, Z., and Li, D. (2025). Association Between Dietary Inflammatory and Oxidative Balance Scores and Skin Cancer Risk: The Mediating Role of Accelerated Phenotypic Aging. Cancers, 18.","DOI":"10.3390\/cancers18010111"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Penha, R.C.C., Onwuka, J.U., Langdon, R., Sandanger, T.M., N\u00f8st, T.H., Vineis, P., Johansson, M., Milne, R.L., Dugu\u00e9, P.A., and Relton, C. (2025). DNA methylation-based clocks, tobacco smoking, and lung cancer risk. BMC Med., 24.","DOI":"10.1186\/s12916-025-04542-9"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s12944-025-02446-4","article-title":"The association of visceral and subcutaneous fat areas with phenotypic age in non-elderly adults, mediated by HOMA-IR and HDL-C","volume":"24","author":"Liu","year":"2025","journal-title":"Lipids Health Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e72020","DOI":"10.2196\/72020","article-title":"Associations Between Dietary Habits and Accelerated Aging and the Establishment of an Accelerated Aging Interpretable Risk Prediction Model via Shapley Additive Explanations: Cross-Sectional Study from Two Representative Populations","volume":"8","author":"Wu","year":"2025","journal-title":"JMIR Aging"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2612796","DOI":"10.1080\/13685538.2026.2612796","article-title":"PhenoAgeAccel mediates the association between metabolic syndrome and cancer risk in males: A cross-sectional NHANES study","volume":"29","author":"Yang","year":"2026","journal-title":"Aging Male"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"123632","DOI":"10.1016\/j.envres.2025.123632","article-title":"Association of residential green space, blue space, and natural environment with osteoarthritis risk: The role of air pollution and phenotypic age acceleration","volume":"292","author":"Bai","year":"2026","journal-title":"Environ. Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"100755","DOI":"10.1016\/j.jnha.2025.100755","article-title":"Associations between dietary patterns and the incidence of idiopathic pulmonary fibrosis: A cohort study","volume":"30","author":"Li","year":"2026","journal-title":"J. Nutr. Health Aging"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1111\/dom.70261","article-title":"Cardiorespiratory fitness and type 2 diabetes risk: A prospective cohort study with mediation analysis of biological aging in the UK Biobank","volume":"28","author":"Liu","year":"2026","journal-title":"Diabetes Obes. Metab."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1186\/s12967-025-06189-9","article-title":"Accelerated biological aging mediates the association between inflammatory markers with Helicobacter pylori infection and mortality","volume":"23","author":"Qiu","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Aliberti, S.M., Funk, R.H.W., Ciaglia, E., Gonnella, J., Giudice, A., Vecchione, C., Puca, A.A., and Capunzo, M. (2023). Old, Nonagenarians, and Centenarians in Cilento, Italy and the Association of Lifespan with the Level of Some Physicochemical Elements in Tap Drinking Water. Nutrients, 15.","DOI":"10.3390\/nu15010218"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Aliberti, S.M., and Capunzo, M. (2025). The Power of Environment: A Comprehensive Review of the Exposome\u2019s Role in Healthy Aging, Longevity, and Preventive Medicine\u2014Lessons from Blue Zones and Cilento. Nutrients, 17.","DOI":"10.3390\/nu17040722"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Aliberti, S.M., Capunzo, M., Galimberti, D., Accardi, G., Aiello, A., Calabr\u00f2, A., Caruso, C., and Candore, G. (2025). Ageing Trajectories: Exposome-Driven Pathobiological Mechanisms and Implications for Prevention from Blue Zones and Italian Longevity Hotspots Such as Cilento and Sicilian Mountain Villages. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26104796"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Aliberti, S.M., Capunzo, M., and Funk, R.H.W. (2025). Systems and Molecular Biology of Longevity and Preventive Medicine: Brain-Energy\u2013Microbiome\u2013Exposome Synergies in Blue Zones and the Cilento Case. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26167887"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/gepi.21789","article-title":"Accounting for population stratification in DNA methylation studies","volume":"38","author":"Barfield","year":"2014","journal-title":"Genet. Epidemiol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.18632\/aging.101900","article-title":"Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: A multi-cohort analysis","volume":"11","author":"Fiorito","year":"2019","journal-title":"Aging"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1186\/s13059-016-1030-0","article-title":"An epigenetic clock analysis of race\/ethnicity, sex, and coronary heart disease","volume":"17","author":"Horvath","year":"2016","journal-title":"Genome Biol."},{"key":"ref_116","unstructured":"Caruso, C. (2025). Chapter 3\u2014Exposome, aging, and longevity: The role of sex and gender differences in health and mortality. Role of Sex and Gender in Aging and Longevity, Academic Press."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nrg3142","article-title":"Epigenetics and the environment: Emerging patterns and implications","volume":"13","author":"Feil","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1126\/science.aad3267","article-title":"Healthy aging: The ultimate preventative medicine","volume":"350","author":"Kaeberlein","year":"2015","journal-title":"Science"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11357-016-9954-6","article-title":"Geroscience and the trans-NIH Geroscience Interest Group, GSIG","volume":"39","author":"Sierra","year":"2017","journal-title":"GeroScience"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"e54870","DOI":"10.7554\/eLife.54870","article-title":"Quantification of the pace of biological aging in humans through a blood test, the DunedinPoAm DNA methylation algorithm","volume":"9","author":"Belsky","year":"2020","journal-title":"eLife"},{"key":"ref_121","unstructured":"World Health Organization (2026, April 23). Ageing and Health, Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/ageing-and-health."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1093\/gerona\/glz075","article-title":"Changing Disease Prevalence, Incidence, and Mortality Among Older Cohorts: The Health and Retirement Study","volume":"74","author":"Crimmins","year":"2019","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Zhang, K., Ma, Y., Luo, Y., Song, Y., Xiong, G., Ma, Y., Sun, X., and Kan, C. (2023). Metabolic diseases and healthy aging: Identifying environmental and behavioral risk factors and promoting public health. Front. Public Health, 11.","DOI":"10.3389\/fpubh.2023.1253506"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1017\/S0029665113003923","article-title":"A life-course approach to healthy ageing: Maintaining physical capability","volume":"73","author":"Kuh","year":"2014","journal-title":"Proc. Nutr. Soc."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Rovira, I.I., Biragyn, A., Brown, L.L., Galis, Z.S., Klauzinska, M., Kotliarova, S.E., Simmons, J.M., Wali, A., Xi, D., and Yarden, R.I. (2025). Health and aging trajectories: Shared and competing risks and resiliencies for chronic diseases associated with aging. A NIH-wide workshop. Front. Public Health, 13.","DOI":"10.3389\/fpubh.2025.1462217"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"e13028","DOI":"10.1111\/acel.13028","article-title":"Reversal of epigenetic aging and immunosenescent trends in humans","volume":"18","author":"Fahy","year":"2019","journal-title":"Aging Cell"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e469","DOI":"10.1016\/S2542-5196(19)30215-3","article-title":"Green spaces and mortality: A systematic review and meta-analysis of cohort studies","volume":"3","author":"Nieuwenhuijsen","year":"2019","journal-title":"Lancet Planet. Health"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"109164","DOI":"10.1016\/j.envint.2024.109164","article-title":"Climate change policies reduce air pollution and increase physical activity: Benefits, costs, inequalities, and indoor exposures","volume":"195","author":"Beevers","year":"2025","journal-title":"Environ. Int."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"21501319251332723","DOI":"10.1177\/21501319251332723","article-title":"Community-Engaged Mental Health and Wellbeing Initiatives in Under-Resourced Settings: A Scoping Review of Primary Studies","volume":"16","author":"Chutiyami","year":"2025","journal-title":"J. Prim. Care Community Health"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1016\/S0140-6736(15)60901-1","article-title":"Safeguarding human health in the Anthropocene epoch: Report of The Rockefeller Foundation-Lancet Commission on planetary health","volume":"386","author":"Whitmee","year":"2015","journal-title":"Lancet"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1056\/NEJMra1807873","article-title":"The Imperative for Climate Action to Protect Health","volume":"380","author":"Haines","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"101032","DOI":"10.1016\/j.progress.2025.101032","article-title":"Healthy cities as catalysts for sustainable development: A systematic review of co-benefits, trade-offs, and solutions to the SDGs","volume":"203","author":"Dehrashid","year":"2026","journal-title":"Prog. Plan."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/5032\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T04:37:45Z","timestamp":1780634265000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/5032"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,2]]},"references-count":132,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27115032"],"URL":"https:\/\/doi.org\/10.3390\/ijms27115032","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,2]]}}}