{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:35:40Z","timestamp":1789011340135,"version":"build-2803163510"},"reference-count":129,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Telomeres, the protective chromosomal ends, progressively shorten and potentially are implicated in the pathogenesis of age-related diseases. In type 2 diabetes (T2DM), telomere shortening may play an important role, but the whole \u2018picture\u2019 remains limited. From a therapeutic perspective, the phytonutrient quercetin appears to be clinically effective and safe for patients with T2DM. Considering the above, we aimed to examine whether quercetin could interfere with telomere length (TL) dynamics. One hundred patients with T2DM on non-insulin medications registered within a primary healthcare facility were stratified by age and sex and randomly assigned to either standard care or standard care plus quercetin (500 mg\/day) for 12 weeks, succeeded by an 8-week washout period and another 12 weeks of supplementation. Of the 88 patients completing the trial, 82 consented to blood sampling for TL measurements. Health assessments and whole blood absolute TL measurements using quantitative polymerase chain reaction (qPCR) were conducted at baseline and study end, and the findings of this subcohort are presented. Quercetin supplementation was associated with a significant increase in mean TL (odds ratio \u2265 2.44; p &lt; 0.05) with a strengthened association after full adjustment for potential confounders through multiple logistic regression analysis (odds ratio = 3.48; p = 0.026), suggesting it as a potentially promising supplementation option. Further studies are needed to confirm this finding, elucidating the underlying molecular mechanisms of quercetin.<\/jats:p>","DOI":"10.3390\/ph17091136","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T03:40:39Z","timestamp":1724902839000},"page":"1136","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Quercetin Intake and Absolute Telomere Length in Patients with Type 2 Diabetes Mellitus: Novel Findings from a Randomized Controlled Before-and-After Study"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6160-8066","authenticated-orcid":false,"given":"Aikaterini E.","family":"Mantadaki","sequence":"first","affiliation":[{"name":"Clinic of Social and Family Medicine, Department of Social Medicine, School of Medicine, University of Crete, 70013 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Baliou","sequence":"additional","affiliation":[{"name":"Laboratory of Toxicology, Medical School, University of Crete, 71003 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3849-3907","authenticated-orcid":false,"given":"Manolis","family":"Linardakis","sequence":"additional","affiliation":[{"name":"Clinic of Social and Family Medicine, Department of Social Medicine, School of Medicine, University of Crete, 70013 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Vakonaki","sequence":"additional","affiliation":[{"name":"Laboratory of Toxicology, Medical School, University of Crete, 71003 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manolis N.","family":"Tzatzarakis","sequence":"additional","affiliation":[{"name":"Laboratory of Toxicology, Medical School, University of Crete, 71003 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3824-2462","authenticated-orcid":false,"given":"Aristides","family":"Tsatsakis","sequence":"additional","affiliation":[{"name":"Laboratory of Toxicology, Medical School, University of Crete, 71003 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanouil K.","family":"Symvoulakis","sequence":"additional","affiliation":[{"name":"Clinic of Social and Family Medicine, Department of Social Medicine, School of Medicine, University of Crete, 70013 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.trsl.2013.05.003","article-title":"Short Telomeres: From Dyskeratosis Congenita to Sporadic Aplastic Anemia and Malignancy","volume":"162","author":"Gramatges","year":"2013","journal-title":"Transl. Res."},{"key":"ref_2","unstructured":"Malavolta, M., and Mocchegiani, E. (2016). Chapter 10\u2014Telomeres, Aging, and Nutrition. Molecular Basis of Nutrition and Aging, Academic Press."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"118341","DOI":"10.1016\/j.lfs.2020.118341","article-title":"Stabilization of Telomere by the Antioxidant Property of Polyphenols: Anti-Aging Potential","volume":"259","author":"Maleki","year":"2020","journal-title":"Life Sci."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ruiz, A., Flores-Gonzalez, J., Buendia-Roldan, I., and Chavez-Galan, L. (2022). Telomere Shortening and Its Association with Cell Dysfunction in Lung Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010425"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1038\/nature05976","article-title":"Replication and Protection of Telomeres","volume":"447","author":"Verdun","year":"2007","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1097\/MCO.0b013e32834121b1","article-title":"Telomeres, Lifestyle, Cancer, and Aging","volume":"14","author":"Shammas","year":"2011","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s00424-009-0728-1","article-title":"Telomere Biology in Healthy Aging and Disease","volume":"459","author":"Oeseburg","year":"2010","journal-title":"Pflug. Arch."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s10522-023-10085-4","article-title":"Telomeres, Cellular Senescence, and Aging: Past and Future","volume":"25","author":"Eppard","year":"2024","journal-title":"Biogerontology"},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1038\/ncomms2602","article-title":"Telomeres Shorten at Equivalent Rates in Somatic Tissues of Adults","volume":"4","author":"Daniali","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"158","DOI":"10.3892\/mmr.2022.12674","article-title":"\u03a4elomerase Inhibitors and Activators in Aging and Cancer: A Systematic Review","volume":"25","author":"Fragkiadaki","year":"2022","journal-title":"Mol. Med. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kakridonis, F., Pneumatikos, S.G., Vakonaki, E., Berdiaki, A., Tzatzarakis, M.N., Fragkiadaki, P., Spandidos, D.A., Baliou, S., Ioannou, P., and Hatzidaki, E. (2023). Telomere Length as a Predictive Biomarker in Osteoporosis (Review). Biomed. Rep., 19.","DOI":"10.3892\/br.2023.1669"},{"key":"ref_13","first-page":"1626","article-title":"Telomere Length and Telomerase Activity in Osteoporosis and Osteoarthritis (Review)","volume":"19","author":"Fragkiadaki","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.3892\/mmr.2020.11274","article-title":"Telomerase and Telomeres in Aging Theory and Chronographic Aging Theory (Review)","volume":"22","author":"Razgonova","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_15","first-page":"111","article-title":"Common Mental Disorders and Association with Telomere Length","volume":"8","author":"Vakonaki","year":"2018","journal-title":"Biomed. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3892\/mmr.2016.5231","article-title":"Telomerase Activity in Pregnancy Complications (Review)","volume":"14","author":"Fragkiadaki","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Apetroaei, M.-M., Fragkiadaki, P., Velescu, B.\u0218., Baliou, S., Renieri, E., Dinu-Pirvu, C.E., Dr\u0103g\u0103nescu, D., Vl\u0103sceanu, A.M., Nedea, M.I., and Udeanu, D.I. (2024). Pharmacotherapeutic Considerations on Telomere Biology: The Positive Effect of Pharmacologically Active Substances on Telomere Length. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25147694"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"50835","DOI":"10.18632\/oncotarget.10615","article-title":"Leukocyte Telomere Length and Mortality Risk in Patients with Type 2 Diabetes","volume":"7","author":"Bonfigli","year":"2016","journal-title":"Oncotarget"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.2337\/db14-1820","article-title":"Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity","volume":"64","author":"Palmer","year":"2015","journal-title":"Diabetes"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Mantadaki, A.E., Linardakis, M., Tsakiri, M., Baliou, S., Fragkiadaki, P., Vakonaki, E., Tzatzarakis, M.N., Tsatsakis, A., and Symvoulakis, E.K. (2024). Benefits of Quercetin on Glycated Hemoglobin, Blood Pressure, PiKo-6 Readings, Night-Time Sleep, Anxiety, and Quality of Life in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial. J. Clin. Med., 13.","DOI":"10.3390\/jcm13123504"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1007\/s00125-019-4934-x","article-title":"Cellular Senescence: At the Nexus between Ageing and Diabetes","volume":"62","author":"Palmer","year":"2019","journal-title":"Diabetologia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"bqab136","DOI":"10.1210\/endocr\/bqab136","article-title":"Role of Cellular Senescence in Type II Diabetes","volume":"162","author":"Narasimhan","year":"2021","journal-title":"Endocrinology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"154799","DOI":"10.1016\/j.metabol.2021.154799","article-title":"Diabetes and Kidney Disease: Emphasis on Treatment with SGLT-2 Inhibitors and GLP-1 Receptor Agonists","volume":"120","author":"Prattichizzo","year":"2021","journal-title":"Metabolism"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Murakami, T., Inagaki, N., and Kondoh, H. (2022). Cellular Senescence in Diabetes Mellitus: Distinct Senotherapeutic Strategies for Adipose Tissue and Pancreatic \u03b2 Cells. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.869414"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"441","DOI":"10.4093\/dmj.2022.0416","article-title":"Regulation of Cellular Senescence in Type 2 Diabetes Mellitus: From Mechanisms to Clinical Applications","volume":"47","author":"Iwasaki","year":"2023","journal-title":"Diabetes Metab. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1002\/med.21702","article-title":"Emerging Use of Senolytics and Senomorphics against Aging and Chronic Diseases","volume":"40","author":"Martel","year":"2020","journal-title":"Med. Res. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.arr.2013.12.006","article-title":"Telomerase Activation: A Potential Key Modulator for Human Healthspan and Longevity","volume":"15","author":"Boccardi","year":"2014","journal-title":"Ageing Res. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s13073-016-0324-x","article-title":"Roles of Telomeres and Telomerase in Cancer, and Advances in Telomerase-Targeted Therapies","volume":"8","author":"Jafri","year":"2016","journal-title":"Genome Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6172","DOI":"10.1038\/s41388-019-0872-9","article-title":"Mechanisms Underlying the Activation of TERT Transcription and Telomerase Activity in Human Cancer: Old Actors and New Players","volume":"38","author":"Yuan","year":"2019","journal-title":"Oncogene"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e158450","DOI":"10.1172\/JCI158450","article-title":"Cellular Senescence: A Key Therapeutic Target in Aging and Diseases","volume":"132","author":"Zhang","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.fitote.2015.09.018","article-title":"Quercetin: A Flavonol with Multifaceted Therapeutic Applications?","volume":"106","year":"2015","journal-title":"Fitoterapia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s40290-022-00444-w","article-title":"Potential Role of Polyphenolic Flavonoids as Senotherapeutic Agents in Degenerative Diseases and Geroprotection","volume":"36","author":"Mbara","year":"2022","journal-title":"Pharm. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.joca.2020.11.006","article-title":"Senolytic Agent Quercetin Ameliorates Intervertebral Disc Degeneration via the Nrf2\/NF-\u03baB Axis","volume":"29","author":"Shao","year":"2021","journal-title":"Osteoarthr. Cartil."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.trsl.2019.07.005","article-title":"Increased Renal Cellular Senescence in Murine High-Fat Diet: Effect of the Senolytic Drug Quercetin","volume":"213","author":"Kim","year":"2019","journal-title":"Transl. Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Aghababaei, F., and Hadidi, M. (2023). Recent Advances in Potential Health Benefits of Quercetin. Pharmaceuticals, 16.","DOI":"10.3390\/ph16071020"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Chiang, M.-C., Tsai, T.-Y., and Wang, C.-J. (2023). The Potential Benefits of Quercetin for Brain Health: A Review of Anti-Inflammatory and Neuroprotective Mechanisms. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076328"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Ioannou, P., and Baliou, S. (2024). The Molecular Mechanisms and Therapeutic Potential of Cranberry, D-Mannose, and Flavonoids against Infectious Diseases: The Example of Urinary Tract Infections. Antibiotics, 13.","DOI":"10.3390\/antibiotics13070593"},{"key":"ref_38","first-page":"e58219","article-title":"The Impact of Three-Month Quercetin Intake on Quality of Life and Anxiety in Patients with Type II Diabetes Mellitus: An Early Data Analysis from a Randomized Controlled Trial","volume":"16","author":"Mantadaki","year":"2024","journal-title":"Cureus"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100250","DOI":"10.1016\/j.phanu.2020.100250","article-title":"Cardio-Metabolic Benefits of Quercetin in Elderly Patients with Metabolic Syndrome","volume":"15","author":"Shatylo","year":"2021","journal-title":"PharmaNutrition"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"O\u2019Callaghan, N.J., and Fenech, M. (2011). A Quantitative PCR Method for Measuring Absolute Telomere Length. Biol. Proced. Online, 13.","DOI":"10.1186\/1480-9222-13-3"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Lai, T.-P., Wright, W.E., and Shay, J.W. (2018). Comparison of Telomere Length Measurement Methods. Philos. Trans. R. Soc. B Biol. Sci., 373.","DOI":"10.1098\/rstb.2016.0451"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"807","DOI":"10.2144\/000112761","article-title":"A Quantitative Real-Time PCR Method for Absolute Telomere Length","volume":"44","author":"Dhillon","year":"2008","journal-title":"BioTechniques"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kahl, V.F.S., Allen, J.A.M., Nelson, C.B., Sobinoff, A.P., Lee, M., Kilo, T., Vasireddy, R.S., and Pickett, H.A. (2020). Telomere Length Measurement by Molecular Combing. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00493"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Lindrose, A.R., McLester-Davis, L.W.Y., Tristano, R.I., Kataria, L., Gadalla, S.M., Eisenberg, D.T.A., Verhulst, S., and Drury, S. (2021). Method Comparison Studies of Telomere Length Measurement Using qPCR Approaches: A Critical Appraisal of the Literature. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0245582"},{"key":"ref_45","unstructured":"(2024, July 14). ISRCTN\u2014ISRCTN13131584: Study on the Benefit of Quercetin Intake in Diabetic Patients Treated with Antidiabetic Tablets. Available online: https:\/\/www.isrctn.com\/ISRCTN13131584."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1002\/gcc.22475","article-title":"Comparison of Different Methods for Telomere Length Measurement in Whole Blood and Blood Cell Subsets: Recommendations for Telomere Length Measurement in Hematological Diseases","volume":"56","author":"Behrens","year":"2017","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/S0165-4608(98)00029-6","article-title":"Comparison of Chromosome Telomere Integrity in Multiple Tissues from Subjects at Different Ages","volume":"105","author":"Butler","year":"1998","journal-title":"Cancer Genet. Cytogenet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1016\/j.ebiom.2015.07.029","article-title":"Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-Supercentenarians","volume":"2","author":"Arai","year":"2015","journal-title":"EBioMedicine"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Vaiserman, A., and Krasnienkov, D. (2021). Telomere Length as a Marker of Biological Age: State-of-the-Art, Open Issues, and Future Perspectives. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.630186"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Shin, D.-Y., Lim, K.M., Park, H.S., Kwon, S., Yoon, S.-S., and Lee, D.-S. (2022). The Importance of Critically Short Telomere in Myelodysplastic Syndrome. Biomark. Res., 10.","DOI":"10.1186\/s40364-022-00426-9"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"15122","DOI":"10.1073\/pnas.1902452116","article-title":"Telomere Shortening Rate Predicts Species Life Span","volume":"116","author":"Whittemore","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","first-page":"7387","article-title":"New Insights from Bidirectional Mendelian Randomization: Causal Relationships between Telomere Length and Mitochondrial DNA Copy Number in Aging Biomarkers","volume":"16","author":"Yan","year":"2024","journal-title":"Aging"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S2213-8587(20)30365-X","article-title":"Diabetes, Metabolic Disease, and Telomere Length","volume":"9","author":"Cheng","year":"2021","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"701","DOI":"10.2337\/dc21-1609","article-title":"Shortened Leukocyte Telomere Length Is Associated With Glycemic Progression in Type 2 Diabetes: A Prospective and Mendelian Randomization Analysis","volume":"45","author":"Cheng","year":"2022","journal-title":"Diabetes Care"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.atherosclerosis.2009.12.021","article-title":"Telomere Length in Atherosclerosis and Diabetes","volume":"209","author":"Salpea","year":"2010","journal-title":"Atherosclerosis"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.ebiom.2019.08.069","article-title":"Senolytics Decrease Senescent Cells in Humans: Preliminary Report from a Clinical Trial of Dasatinib plus Quercetin in Individuals with Diabetic Kidney Disease","volume":"47","author":"Hickson","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1111\/acel.12344","article-title":"The Achilles\u2019 Heel of Senescent Cells: From Transcriptome to Senolytic Drugs","volume":"14","author":"Zhu","year":"2015","journal-title":"Aging Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"S296","DOI":"10.1093\/advances\/nmz026","article-title":"Plant-Rich Dietary Patterns, Plant Foods and Nutrients, and Telomere Length","volume":"10","author":"Molinuevo","year":"2019","journal-title":"Adv. Nutr."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1007\/s12603-023-1948-3","article-title":"Effects of Vitamin D Supplementation on Telomere Length: An Analysis of Data from the Randomised Controlled D-Health Trial","volume":"27","author":"Rahman","year":"2023","journal-title":"J. Nutr. Health Aging"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.bbi.2012.09.004","article-title":"Omega-3 Fatty Acids, Oxidative Stress, and Leukocyte Telomere Length: A Randomized Controlled Trial","volume":"28","author":"Epel","year":"2013","journal-title":"Brain Behav. Immun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.nut.2013.09.013","article-title":"Telomere Shortening in Elderly Individuals with Mild Cognitive Impairment May Be Attenuated with \u03c9-3 Fatty Acid Supplementation: A Randomized Controlled Pilot Study","volume":"30","author":"Parletta","year":"2014","journal-title":"Nutrition"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Freitas-Simoes, T.-M., Cof\u00e1n, M., Blasco, M.A., Sober\u00f3n, N., Foronda, M., Serra-Mir, M., Roth, I., Valls-Pedret, C., Dom\u00e9nech, M., and Ponferrada-Ariza, E. (2018). Walnut Consumption for Two Years and Leukocyte Telomere Attrition in Mediterranean Elders: Results of a Randomized Controlled Trial. Nutrients, 10.","DOI":"10.3390\/nu10121907"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1007\/s00394-016-1231-z","article-title":"One-Carbon Metabolites and Telomere Length in a Prospective and Randomized Study of B- and\/or D-Vitamin Supplementation","volume":"56","author":"Pusceddu","year":"2017","journal-title":"Eur. J. Nutr."},{"key":"ref_64","unstructured":"(2024, July 20). Exploring the Effects of Dasatinib, Quercetin, and Fisetin on DNA Methylation Clocks: A Longitudinal Study on Senolytic Interventions\u2014PMC, Available online: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10929829\/."},{"key":"ref_65","first-page":"22445","article-title":"Hyperbaric Oxygen Therapy Increases Telomere Length and Decreases Immunosenescence in Isolated Blood Cells: A Prospective Trial","volume":"12","author":"Hachmo","year":"2020","journal-title":"Aging"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"559","DOI":"10.5665\/sleep.5526","article-title":"Insomnia and Telomere Length in Older Adults","volume":"39","author":"Carroll","year":"2016","journal-title":"Sleep"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.5664\/jcsm.7532","article-title":"Long Sleep Duration, Insomnia, and Insomnia with Short Objective Sleep Duration Are Independently Associated With Short Telomere Length","volume":"14","author":"Tempaku","year":"2018","journal-title":"J. Clin. Sleep Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2930","DOI":"10.18632\/aging.203993","article-title":"Association between Sleep Parameters and Longitudinal Shortening of Telomere Length","volume":"14","author":"Jin","year":"2022","journal-title":"Aging"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.maturitas.2017.10.008","article-title":"Gender-Specific Associations between Quality of Life and Leukocyte Telomere Length","volume":"107","author":"Choi","year":"2018","journal-title":"Maturitas"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1093\/ageing\/afp256","article-title":"Telomere Length and Psychological Well-Being in Patients with Chronic Heart Failure","volume":"39","author":"Huzen","year":"2010","journal-title":"Age Ageing"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1080\/08870446.2018.1509977","article-title":"One \u2018Knows\u2019: Self-Rated Health and Telomere Length among Ex-Prisoners of War","volume":"33","author":"Tsur","year":"2018","journal-title":"Psychol. Health"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/jhh.2016.45","article-title":"The Impact of Hypertension on Leukocyte Telomere Length: A Systematic Review and Meta-Analysis of Human Studies","volume":"31","author":"Tellechea","year":"2017","journal-title":"J. Hum. Hypertens."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/sj.jhh.1002314","article-title":"Telomere Length May Be Associated with Hypertension","volume":"22","author":"Lung","year":"2008","journal-title":"J. Hum. Hypertens."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/s11010-012-1276-0","article-title":"Accelerated Aging as Evidenced by Increased Telomere Shortening and Mitochondrial DNA Depletion in Patients with Type 2 Diabetes","volume":"365","author":"Monickaraj","year":"2012","journal-title":"Mol. Cell. Biochem."},{"key":"ref_75","unstructured":"del Moral, A.M., and Aguilera Garc\u00eda, C.M. (2018). Chapter 12\u2014Aging, Telomere Integrity, and Antioxidant Food. Obesity, Academic Press."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.mad.2017.04.004","article-title":"Telomere Shortening during Aging: Attenuation by Antioxidants and Anti-Inflammatory Agents","volume":"164","author":"Prasad","year":"2017","journal-title":"Mech. Ageing Dev."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"D\u2019Angelo, S. (2023). Diet and Aging: The Role of Polyphenol-Rich Diets in Slow Down the Shortening of Telomeres: A Review. Antioxidants, 12.","DOI":"10.3390\/antiox12122086"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1016\/j.biopha.2019.01.035","article-title":"Quercetin Based Derivatives as Sirtuin Inhibitors","volume":"111","author":"Heger","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1002\/ptr.8168","article-title":"Exploring the Therapeutic Potential of Quercetin: A Focus on Its Sirtuin-Mediated Benefits","volume":"38","author":"Ungurianu","year":"2024","journal-title":"Phytother. Res."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Cui, Z., Zhao, X., Amevor, F.K., Du, X., Wang, Y., Li, D., Shu, G., Tian, Y., and Zhao, X. (2022). Therapeutic Application of Quercetin in Aging-Related Diseases: SIRT1 as a Potential Mechanism. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.943321"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Rahnasto-Rilla, M., Tyni, J., Huovinen, M., Jarho, E., Kulikowicz, T., Ravichandran, S., Bohr, V.A., Ferrucci, L., Lahtela-Kakkonen, M., and Moaddel, R. (2018). Natural Polyphenols as Sirtuin 6 Modulators. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-22388-5"},{"key":"ref_82","first-page":"498","article-title":"Quercetin Induces Bladder Cancer Cells Apoptosis by Activation of AMPK Signaling Pathway","volume":"6","author":"Su","year":"2016","journal-title":"Am. J. Cancer Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1111\/1759-7714.13925","article-title":"Quercetin Induces Pro-Apoptotic Autophagy via SIRT1\/AMPK Signaling Pathway in Human Lung Cancer Cell Lines A549 and H1299 In Vitro","volume":"12","author":"Guo","year":"2021","journal-title":"Thorac. Cancer"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.bcp.2012.07.016","article-title":"Quercetin and Its Metabolites Improve Vessel Function by Inducing eNOS Activity via Phosphorylation of AMPK","volume":"84","author":"Shen","year":"2012","journal-title":"Biochem. Pharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Jacczak, B., Rubi\u015b, B., and Toto\u0144, E. (2021). Potential of Naturally Derived Compounds in Telomerase and Telomere Modulation in Skin Senescence and Aging. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126381"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Khan, F., Niaz, K., Maqbool, F., Ismail Hassan, F., Abdollahi, M., Nagulapalli Venkata, K.C., Nabavi, S.M., and Bishayee, A. (2016). Molecular Targets Underlying the Anticancer Effects of Quercetin: An Update. Nutrients, 8.","DOI":"10.3390\/nu8090529"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Ganesan, K., and Xu, B. (2018). Telomerase Inhibitors from Natural Products and Their Anticancer Potential. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010013"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Parekh, N., Garg, A., Choudhary, R., Gupta, M., Kaur, G., Ramniwas, S., Shahwan, M., Tuli, H.S., and Sethi, G. (2023). The Role of Natural Flavonoids as Telomerase Inhibitors in Suppressing Cancer Growth. Pharmaceuticals, 16.","DOI":"10.3390\/ph16040605"},{"key":"ref_89","unstructured":"Cui, S., Wu, X., Wang, Z., Guo, Y., and Xu, R. (2024, July 22). Quercetin Regulates Telomere-Binding Proteins Expression of POT1, TRF1, TRF2 TO Inhibit Proliferation and Induce Apoptosis in AML THP-1 Cells. Available online: https:\/\/library.ehaweb.org\/eha\/2017\/22nd\/182385\/ruirong.xu.quercetin.regulates.telomere-binding.proteins.expression.of.pot1.html."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1179\/102453311X13085644680104","article-title":"Quercetin-Induced Apoptosis Involves Increased hTERT Enzyme Activity of Leukemic Cells","volume":"16","author":"Avci","year":"2011","journal-title":"Hematology"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s00005-023-00669-w","article-title":"A Comprehensive Study on the Anti-Cancer Effects of Quercetin and Its Epigenetic Modifications in Arresting Progression of Colon Cancer Cell Proliferation","volume":"71","author":"Bhatiya","year":"2023","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Zhu, J., Cheng, X., Naumovski, N., Hu, L., and Wang, K. (2023). Epigenetic Regulation by Quercetin: A Comprehensive Review Focused on Its Biological Mechanisms. Crit. Rev. Food Sci. Nutr., 1\u201320.","DOI":"10.1080\/10408398.2023.2278760"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"5300","DOI":"10.1073\/pnas.0609367104","article-title":"High-Throughput Telomere Length Quantification by FISH and Its Application to Human Population Studies","volume":"104","author":"Canela","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Tsatsakis, A., Tsoukalas, D., Fragkiadaki, P., Vakonaki, E., Tzatzarakis, M., Sarandi, E., Nikitovic, D., Tsilimidos, G., and Alegakis, A.K. (2019). Developing BIOTEL: A Semi-Automated Spreadsheet for Estimating Telomere Length and Biological Age. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.00084"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"5621","DOI":"10.1007\/s11033-021-06496-6","article-title":"The Advancement of Telomere Quantification Methods","volume":"48","author":"Dweck","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"379","DOI":"10.18632\/aging.100462","article-title":"Beyond Average: Potential for Measurement of Short Telomeres","volume":"4","author":"Vera","year":"2012","journal-title":"Aging"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Liehr, T. (2017). Telomere Length Measurement by FISH. Fluorescence In Situ Hybridization (FISH): Application Guide, Springer.","DOI":"10.1007\/978-3-662-52959-1"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"438","DOI":"10.5694\/j.1326-5377.2003.tb05627.x","article-title":"Inclusion of Patients in Clinical Trial Analysis: The Intention-to-Treat Principle","volume":"179","author":"Heritier","year":"2003","journal-title":"Med. J. Aust."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1007\/s11357-022-00536-0","article-title":"Senescent Macrophages in the Human Adipose Tissue as a Source of Inflammaging","volume":"44","author":"Matacchione","year":"2022","journal-title":"Geroscience"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3758\/BF03193146","article-title":"G*Power 3: A Flexible Statistical Power Analysis Program for the Social, Behavioral, and Biomedical Sciences","volume":"39","author":"Faul","year":"2007","journal-title":"Behav. Res. Methods"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.3758\/BRM.41.4.1149","article-title":"Statistical Power Analyses Using G*Power 3.1: Tests for Correlation and Regression Analyses","volume":"41","author":"Faul","year":"2009","journal-title":"Behav. Res. Methods"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1016\/j.bbi.2012.05.011","article-title":"Omega-3 Supplementation Lowers Inflammation in Healthy Middle-Aged and Older Adults: A Randomized Controlled Trial","volume":"26","author":"Belury","year":"2012","journal-title":"Brain Behav. Immun."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1200\/JCO.2015.61.6375","article-title":"Randomized Trial Comparing Telephone Versus In-Person Weight Loss Counseling on Body Composition and Circulating Biomarkers in Women Treated for Breast Cancer: The Lifestyle, Exercise, and Nutrition (LEAN) Study","volume":"34","author":"Harrigan","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s10549-018-4895-7","article-title":"Randomized Controlled Trial of Weight Loss versus Usual Care on Telomere Length in Women with Breast Cancer: The Lifestyle, Exercise, and Nutrition (LEAN) Study","volume":"172","author":"Sanft","year":"2018","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Opstad, T.B., Alexander, J., Aaseth, J.O., Larsson, A., Seljeflot, I., and Alehagen, U. (2022). Selenium and Coenzyme Q10 Intervention Prevents Telomere Attrition, with Association to Reduced Cardiovascular Mortality\u2014Sub-Study of a Randomized Clinical Trial. Nutrients, 14.","DOI":"10.3390\/nu14163346"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1017\/S0007114521001549","article-title":"Minimal Changes in Telomere Length after a 12-Week Dietary Intervention with Almonds in Mid-Age to Older, Overweight and Obese Australians: Results of a Randomised Clinical Trial","volume":"127","author":"Ward","year":"2022","journal-title":"Br. J. Nutr."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1152\/japplphysiol.00587.2015","article-title":"Increased Expression of Telomere-Regulating Genes in Endurance Athletes with Long Leukocyte Telomeres","volume":"120","author":"Denham","year":"2016","journal-title":"J. Appl. Physiol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e032513","DOI":"10.1136\/bmjopen-2019-032513","article-title":"A Multidisciplinary Approach to Mental Illness: Do Inflammation, Telomere Length and Microbiota Form a Loop? A Protocol for a Cross-Sectional Study on the Complex Relationship between Inflammation, Telomere Length, Gut Microbiota and Psychiatric Disorders","volume":"10","author":"Manchia","year":"2020","journal-title":"BMJ Open"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1186\/s13063-022-06257-1","article-title":"Aerobic Exercise and Telomere Length in Patients with Systolic Heart Failure: Protocol Study for a Randomized Controlled Trial","volume":"23","author":"Franzoni","year":"2022","journal-title":"Trials"},{"key":"ref_110","first-page":"218","article-title":"Association of Nutraceutical Supplements with Longer Telomere Length","volume":"44","author":"Tsoukalas","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3892\/mmr.2023.13119","article-title":"A Novel Nutraceutical Formulation Increases Telomere Length and Activates Telomerase Activity in Middle-aged Rats","volume":"28","author":"Tsatsakis","year":"2023","journal-title":"Mol. Med. Rep."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"4516","DOI":"10.18632\/oncotarget.27000","article-title":"A Novel Curcumin Analog Inhibits Canonical and Non-Canonical Functions of Telomerase through STAT3 and NF-\u03baB Inactivation in Colorectal Cancer Cells","volume":"10","author":"Chung","year":"2019","journal-title":"Oncotarget"},{"key":"ref_113","unstructured":"(2024, July 20). Precision in qPCR\u2014GR. Available online: https:\/\/www.thermofisher.com\/tr\/en\/home\/life-science\/pcr\/real-time-pcr\/real-time-pcr-learning-center\/gene-expression-analysis-real-time-pcr-information\/precision-qpcr.html."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.ymeth.2010.01.005","article-title":"A Practical Approach to RT-qPCR\u2014Publishing Data That Conform to the MIQE Guidelines","volume":"50","author":"Taylor","year":"2010","journal-title":"Methods"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.ymeth.2010.01.025","article-title":"Statistical Aspects of Quantitative Real-Time PCR Experiment Design","volume":"50","author":"Kitchen","year":"2010","journal-title":"Methods"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing Real-Time PCR Data by the Comparative CT Method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s10389-019-01030-2","article-title":"Prevalence of Multiple Behavioral Risk Factors for Chronic Diseases in Medical Students and Associations with Their Academic Performance","volume":"28","author":"Linardakis","year":"2020","journal-title":"J. Public Health"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s10389-015-0683-6","article-title":"Relationship of Behavioral Risk Factors for Chronic Diseases and Preventive Health Services Utilization among Adults, Aged 50+, from Eleven European Countries","volume":"23","author":"Linardakis","year":"2015","journal-title":"J. Public Health"},{"key":"ref_120","first-page":"e56711","article-title":"Multiple Behavioral Risk Factors As Assets for Chronic Disease Prevention: Observations From Urban Primary Care Settings in Crete, Greece","volume":"16","author":"Symvoulakis","year":"2024","journal-title":"Cureus"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1093\/biomet\/78.3.691","article-title":"A Note on a General Definition of the Coefficient of Determination","volume":"78","author":"Nagelkerke","year":"1991","journal-title":"Biometrika"},{"key":"ref_122","unstructured":"(2024, April 25). ICH Harmonised Guideline Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice ICH E6(R2) ICH Consensus Guideline. Available online: https:\/\/ichgcp.net\/home."},{"key":"ref_123","unstructured":"(2024, March 22). European Medicines Agency Guideline for Good Clinical Practice E6 (R2). Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/ich-guideline-good-clinical-practice-e6r2-4-step-2b_en.pdf."},{"key":"ref_124","unstructured":"(2024, March 22). European Parliament and the Council of the European Union Regulation (EU) No 536\/2014 of the European Parliament and of the Council of 16 April 2014 on Clinical Trials on Medicinal Products for Human Use, and Repealing Directive 2001\/20\/EC. Available online: https:\/\/health.ec.europa.eu\/document\/download\/f724d198-9ec8-4cad-9ce7-b6d2ac1ec44e_en."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"World Medical Association (2013). World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA, 310, 2191\u20132194.","DOI":"10.1001\/jama.2013.281053"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"c869","DOI":"10.1136\/bmj.c869","article-title":"CONSORT 2010 Explanation and Elaboration: Updated Guidelines for Reporting Parallel Group Randomised Trials","volume":"340","author":"Moher","year":"2010","journal-title":"BMJ"},{"key":"ref_127","unstructured":"World Health Organization (2005). Handbook for Good Clinical Research Practice (GCP): Guidance for Implementation, World Health Organization. Available online: https:\/\/iris.who.int\/bitstream\/handle\/10665\/43392\/924159392X_eng.pdf."},{"key":"ref_128","unstructured":"International Council For Harmonisation (ICH) (2024, July 14). Harmonised Guideline on Genomic Sampling and Management of Genomic Data E18. Available online: https:\/\/database.ich.org\/sites\/default\/files\/E18_Guideline.pdf."},{"key":"ref_129","unstructured":"European Medicines Agency (EMA) (2024, July 14). ICH Guideline E18 on Genomic Sampling and Management of Genomic Data. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/ich-guideline-e18-genomic-sampling-and-management-genomic-data-step-3_en.pdf."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/9\/1136\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:44:46Z","timestamp":1760111086000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/9\/1136"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,29]]},"references-count":129,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ph17091136"],"URL":"https:\/\/doi.org\/10.3390\/ph17091136","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,29]]}}}