{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:07:12Z","timestamp":1789020432837,"version":"build-2803163510"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lifestyle modification programs (LMP) such as diabetes prevention programs may influence phenotypic aging trajectories, but evidence in Middle Eastern populations remains limited. This study examined the effects of a structured LMP on phenotypic age (PhenoAge) as the primary endpoint and circulating sclerostin (SOST) and growth differentiation factor-15 (GDF-15) as secondary endpoints in a cohort of Arab adults with prediabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants and Methods<\/jats:title>\n                    <jats:p>\n                      In this randomized clinical trial (RCT), a total of 181 adults (130 males, 51 females; mean age 50.8 \u00b1 10.9 years, body mass index, BMI 30.0 \u00b1 4.8\u00a0kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) were enrolled. Participants were allocated to either a structured LMP or Control Group (CG) and followed for 6 months. The LMP group was requested to reduce weight by 5%, moderate exercise (150\u00a0min\/week), reduce fat intake (30%) and increase fiber intake (15g\/1\u00a0kcal). CG was given brochure. PhenoAge was calculated and assessed alongside anthropometrics, blood biomarkers (HbA1c, fasting glucose, albumin, creatinine, GDF15, SOST), and dietary parameters at baseline and after 6 months.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with the CG, participants in the lifestyle modification program (LMP) showed a significant reduction in PhenoAge (\u22124.9 vs. +1.3 years; between-group\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001). Significant between-group improvements were also observed in weight (\u22125.7\u00a0kg), BMI (\u22122.0\u00a0kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ), waist circumference (\u22126.3\u00a0cm), and HbA1c (\u22120.4%; all\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001). Neither GDF-15 nor SOST demonstrated a significant intervention-specific effect.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A structured lifestyle intervention significantly improved PhenoAge, accompanied by improvements in metabolic parameters in Arab adults with prediabetes. Changes in GDF-15 and SOST appeared time-dependent rather than intervention-specific. These findings support lifestyle modification as a potential strategy to slow a composite clinical measure of biological aging. ClinicalTrial Registration (NCT06440681).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fragi.2026.1809697","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:31:13Z","timestamp":1789018273000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Structured lifestyle modification and biological aging: effects on PhenoAge, sclerostin, and GDF-15 in arab adults with prediabetes"],"prefix":"10.3389","volume":"7","author":[{"given":"Ahmed","family":"Alenezi","sequence":"first","affiliation":[{"name":"Chair for Biomarkers of Chronic Diseases, Department of Biochemistry, College of Science, King Saud University","place":["Riyadh, Saudi Arabia"]},{"name":"North Medical Tower Hospital","place":["Arar, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun","family":"Sabico","sequence":"additional","affiliation":[{"name":"Chair for Biomarkers of Chronic Diseases, Department of Biochemistry, College of Science, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah M.","family":"Alnaami","sequence":"additional","affiliation":[{"name":"Chair for Biomarkers of Chronic Diseases, Department of Biochemistry, College of Science, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed D.","family":"Hussain","sequence":"additional","affiliation":[{"name":"Chair for Biomarkers of Chronic Diseases, Department of Biochemistry, College of Science, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed S.","family":"Elrobh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Science, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasser M.","family":"Al-Daghri","sequence":"additional","affiliation":[{"name":"Chair for Biomarkers of Chronic Diseases, Department of Biochemistry, College of Science, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.3390\/biomedicines13071589","article-title":"Investigating the role of GDF-15 in diabetes and obesity: a comprehensive analysis of a cohort from the KDEP study","volume":"13","author":"Abubaker","year":"2025","journal-title":"Biomedicines"},{"key":"B2","unstructured":"2026"},{"key":"B3","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1530\/EJE-10-0241","article-title":"Adiposity and insulin resistance correlate with telomere length in middle-aged arabs: the influence of circulating adiponectin","volume":"163","author":"Al-Attas","year":"2010","journal-title":"Eur. J. Endocrinol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"103276","DOI":"10.1016\/j.sjbs.2022.03.026","article-title":"Endotoxemia, vitamin D and premature biological ageing in Arab adults with different metabolic states","volume":"29","author":"Al-Daghri","year":"2022","journal-title":"Saudi J. Biol. Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1111\/jdi.13531","article-title":"Efficacy of lifestyle intervention program for Arab women with prediabetes using social media as an alternative platform of delivery","volume":"12","author":"Al-Hamdan","year":"2021","journal-title":"J. Diabetes Investig."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1392675","DOI":"10.3389\/fendo.2024.1392675","article-title":"Evaluating the correlation of sclerostin levels with obesity and type 2 diabetes in a multiethnic population living in Kuwait","volume":"15","author":"Alramah","year":"2024","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"B7","doi-asserted-by":"publisher","first-page":"S27","DOI":"10.2337\/dc26-S002","article-title":"Diagnosis and classification of diabetes: standards of care in Diabetes\u20142026","volume":"49","year":"2026","journal-title":"Diabetes Care"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1002\/jbmr.1560","article-title":"Weight loss in Obese older adults increases serum sclerostin and impairs hip geometry but both are prevented by exercise training","volume":"27","author":"Armamento-Villareal","year":"2012","journal-title":"J. Bone Min. Res."},{"key":"B9","doi-asserted-by":"publisher","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":"Bischoff-Ferrari","year":"2025","journal-title":"Nat. Aging"},{"key":"B10","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.nutres.2025.06.010","article-title":"Integrating biological age, epigenetic clocks, and telomere length in precision nutrition strategies for chronic disease management: potential frameworks and ongoing challenges","volume":"140","author":"Carvalho","year":"2025","journal-title":"Nutr. Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.mad.2013.01.004","article-title":"A novel statistical approach shows evidence for multi-system physiological dysregulation during aging","volume":"134","author":"Cohen","year":"2013","journal-title":"Mech. Ageing Dev."},{"key":"B12","doi-asserted-by":"publisher","first-page":"100046","DOI":"10.1016\/j.ahjo.2021.100046","article-title":"Growth differentiation factor-15, a novel systemic biomarker of oxidative stress, inflammation, and cellular aging: potential role in cardiovascular diseases","volume":"9","author":"di Candia","year":"2021","journal-title":"Am. Heart J. Plus"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2327","DOI":"10.1093\/eurheartj\/ehn339","article-title":"Growth-differentiation factor-15 for early risk stratification in patients with acute chest pain","volume":"29","author":"Eggers","year":"2008","journal-title":"Eur. Heart J."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1417625","DOI":"10.3389\/fragi.2024.1417625","article-title":"Examining nutrition strategies to influence DNA methylation and epigenetic clocks: a systematic review of clinical trials","volume":"5","author":"Garc\u00eda-Garc\u00eda","year":"2024","journal-title":"Front. Aging"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.1210\/jc.2011-2958","article-title":"Circulating sclerostin levels and bone turnover in type 1 and type 2 diabetes","volume":"97","author":"Gennari","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B16","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1159\/000547072","article-title":"Sclerostin: a potential link between osteoporosis and alzheimer\u2019s disease","volume":"25","author":"Guo","year":"2025","journal-title":"Neurodegener. Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.molcel.2012.10.016","article-title":"Genome-wide methylation profiles reveal quantitative views of human aging rates","volume":"49","author":"Hannum","year":"2013","journal-title":"Mol. Cell"},{"key":"B18","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1177\/1535370220968802","article-title":"The use of DNA methylation clock in aging research","volume":"246","author":"He","year":"2020","journal-title":"Exp. Biol. Med. (Maywood)"},{"key":"B19","doi-asserted-by":"publisher","first-page":"R115","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":"B20","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.3390\/nu17061060","article-title":"Epigenetic aging acceleration in obesity is slowed Down by nutritional ketosis following very low-calorie ketogenic diet (VLCKD): a new perspective to reverse biological age","volume":"17","author":"Izquierdo","year":"2025","journal-title":"Nutrients"},{"key":"B21","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/j.cell.2014.10.039","article-title":"Geroscience: linking aging to chronic disease","volume":"159","author":"Kennedy","year":"2014","journal-title":"Cell"},{"key":"B22","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.molmet.2017.12.016","article-title":"Exercise increases circulating GDF15 in humans","volume":"9","author":"Kleinert","year":"2018","journal-title":"Mol. Metab."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e70224","DOI":"10.1111\/acel.70224","article-title":"Epigenetic age acceleration and cardiometabolic biomarkers in response to weight-loss dietary interventions among Obese individuals: the MACRO trial","volume":"24","author":"Kou","year":"2025","journal-title":"Aging Cell"},{"key":"B24","doi-asserted-by":"publisher","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 (Albany NY)"},{"key":"B25","doi-asserted-by":"publisher","first-page":"156332","DOI":"10.1016\/j.metabol.2025.156332","article-title":"The bone-heart axis: a crucial dialogue in cardiovascular disease","volume":"170","author":"Liu","year":"2025","journal-title":"Metabolism"},{"key":"B26","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1186\/s13148-024-01756-1","article-title":"Influence of physical activity on the epigenetic clock: evidence from a Japanese cross-sectional study","volume":"16","author":"Nagata","year":"2024","journal-title":"Clin. Epigenetics"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.1007\/s11357-022-00586-4","article-title":"Telomere length and epigenetic clocks as markers of cellular aging: a comparative study","volume":"44","author":"Pearce","year":"2022","journal-title":"Geroscience"},{"key":"B28","doi-asserted-by":"publisher","first-page":"837575","DOI":"10.3389\/fragi.2022.837575","article-title":"Growth differentiation Factor-15 in immunity and aging","volume":"3","author":"Pence","year":"2022","journal-title":"Front. Aging"},{"key":"B29","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1177\/0890117120906958","article-title":"The impact of health promotion interventions on telomere length: a systematic review","volume":"34","author":"Qiao","year":"2020","journal-title":"Am. J. Health Promot"},{"key":"B30","doi-asserted-by":"publisher","first-page":"106423","DOI":"10.1016\/j.appet.2022.106423","article-title":"Effects of acute exercise and exercise training on plasma GDF15 concentrations and associations with appetite and cardiometabolic health in individuals with overweight or obesity - a secondary analysis of a randomized controlled trial","volume":"182","author":"Quist","year":"2023","journal-title":"Appetite"},{"key":"B31","doi-asserted-by":"publisher","first-page":"102974","DOI":"10.1016\/j.arr.2025.102974","article-title":"Exercise-induced inflammatory and metabolic adaptations in ageing: a meta-analytic compendium","volume":"114","author":"Sheldon","year":"2026","journal-title":"Ageing Res. Rev."},{"key":"B32","doi-asserted-by":"publisher","first-page":"105874","DOI":"10.1016\/j.puhe.2025.105874","article-title":"Physical activity paradox and aging: a population-based study on the association of domain-specific physical activity with biological aging","volume":"247","author":"Song","year":"2025","journal-title":"Public Health"},{"key":"B33","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1016\/j.advms.2025.10.003","article-title":"The role of sclerostin in the development and progression of cardiovascular diseases-a potential biomarker?","volume":"70","author":"Stelmaszek","year":"2025","journal-title":"Adv. Med. Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1666","DOI":"10.1002\/ehf2.14738","article-title":"Prognostic significance of growth differentiation factor-15 across age in chronic heart failure","volume":"11","author":"Teramoto","year":"2024","journal-title":"Esc. Heart Fail"},{"key":"B35","doi-asserted-by":"publisher","first-page":"e3656","DOI":"10.1210\/clinem\/dgaf164","article-title":"Effect of ethnicity on the relationship between telomere length and metabolic markers in Kuwait","volume":"110","author":"Thanaraj","year":"2025","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B36","doi-asserted-by":"publisher","first-page":"e3101","DOI":"10.1210\/clinem\/dgae859","article-title":"Effect of vitamin D3, Omega-3 fatty acids, and exercise on serum sclerostin levels and bone turnover markers","volume":"110","author":"Tsourdi","year":"2025","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-025-02076-9","article-title":"Epigenetic age deceleration reflects exercise-induced cardiorespiratory fitness improvements","author":"Van Damme","year":"2026","journal-title":"Geroscience"},{"key":"B38","doi-asserted-by":"publisher","first-page":"464","DOI":"10.3390\/nu12020464","article-title":"Effects of A 12-Month intensive lifestyle monitoring program in predominantly overweight\/obese Arab adults with prediabetes","volume":"12","author":"Wani","year":"2020","journal-title":"Nutrients"},{"key":"B39","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/s43587-022-00357-y","article-title":"Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial","volume":"3","author":"Waziry","year":"2023","journal-title":"Nat. Aging"},{"key":"B40","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1111\/jdi.14404","article-title":"The effect of exercise on GDF-15 levels in individuals with prediabetes: a randomized controlled trial","volume":"16","author":"Y\u0131ld\u0131r\u0131m Ayaz","year":"2025","journal-title":"J. Diabetes Investig."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1680745","DOI":"10.3389\/fpubh.2025.1680745","article-title":"About half of older adults have two or more chronic conditions at the same time: a systematic review and meta-analysis","volume":"13","author":"Zhu","year":"2025","journal-title":"Front. Public Health"}],"container-title":["Frontiers in Aging"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fragi.2026.1809697\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:31:15Z","timestamp":1789018275000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fragi.2026.1809697\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,10]]},"references-count":41,"alternative-id":["10.3389\/fragi.2026.1809697"],"URL":"https:\/\/doi.org\/10.3389\/fragi.2026.1809697","relation":{},"ISSN":["2673-6217"],"issn-type":[{"value":"2673-6217","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,10]]},"article-number":"1809697"}}