{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:20:25Z","timestamp":1790709625410,"version":"4.1.0"},"reference-count":251,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Aging is associated with complex immune dysfunction that contributes to the onset and progression of the \u201cgeriatric giants\u201d, including frailty, sarcopenia, cognitive decline, falls, and incontinence. Central to these conditions is immunosenescence, marked by thymic involution, the loss of na\u00efve T cells, T-cell exhaustion, impaired B-cell class switch recombination, and increased autoreactivity. Concurrently, innate immunity deteriorates due to macrophage, neutrophil, and NK cell dysfunction, while chronic low-grade inflammation\u2014or \u201cinflammaging\u201d\u2014amplifies systemic decline. Key molecular pathways such as NF-\u03baB, mTOR, and the NLRP3 inflammasome mediate immune aging, interacting with oxidative stress, mitochondrial dysfunction, and epigenetic modifications. These processes not only impair infection control and vaccine responsiveness but also promote tissue degeneration and multimorbidity. This review explores emerging interventions\u2014ranging from senolytics and immunonutrition to microbiome-targeted therapies and exercise\u2014that may restore immune homeostasis and extend healthspan. Despite advances, challenges remain in translating immunological insights into clinical strategies tailored to older adults. Standardization in microbiome trials and safety optimization in senolytic therapies are critical next steps. Integrating geroscience into clinical care could help to mitigate the burden of aging-related diseases by targeting fundamental drivers of immune dysfunction.<\/jats:p>","DOI":"10.3390\/medsci13030100","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T14:05:47Z","timestamp":1753711547000},"page":"100","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Immunosenescence and the Geriatric Giants: Molecular Insights into Aging and Healthspan"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8733-6441","authenticated-orcid":false,"given":"Deasy","family":"Fetarayani","sequence":"first","affiliation":[{"name":"Division of Allergy and Clinical Immunology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"},{"name":"Department of Internal Medicine, Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6850-4981","authenticated-orcid":false,"given":"Mega","family":"Kahdina","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia"},{"name":"Internal Medicine Study Program, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alief","family":"Waitupu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia"},{"name":"Internal Medicine Study Program, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laras","family":"Pratiwi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia"},{"name":"Internal Medicine Study Program, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukti Citra","family":"Ningtyas","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia"},{"name":"Internal Medicine Study Program, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galih Januar","family":"Adytia","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia"},{"name":"Internal Medicine Study Program, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5730-2013","authenticated-orcid":false,"given":"Henry","family":"Sutanto","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia"},{"name":"Internal Medicine Study Program, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1007\/s12603-021-1640-4","article-title":"Osteosarcopenia: A Geriatric Giant of the XXI Century","volume":"25","author":"Duque","year":"2021","journal-title":"J. Nutr. Health Aging"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"xi\u2013xii","DOI":"10.1016\/j.cger.2017.05.001","article-title":"The New Geriatric Giants","volume":"33","author":"Morley","year":"2017","journal-title":"Clin. Geriatr. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"em277","DOI":"10.29333\/ejgm\/9695","article-title":"The Cumulative Impact of Sarcopenia, Frailty, Malnutrition, and Cachexia on Other Geriatric Syndromes in Hospitalized Elderly","volume":"18","author":"Rasheedy","year":"2021","journal-title":"Electron. J. Gen Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"455","DOI":"10.7861\/clinmedicine.16-5-455","article-title":"Sarcopenia and Frailty: New Challenges for Clinical Practice","volume":"16","author":"Dodds","year":"2016","journal-title":"Clin. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"107","DOI":"10.36516\/jocass.1117649","article-title":"The Relationship Between Urinary Incontinence and Sarcopenia in Patients with Dementia","volume":"5","author":"Dost","year":"2022","journal-title":"Cukurova Anestezi Cerrah-Bilim. Derg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2695","DOI":"10.1016\/j.clnu.2019.12.014","article-title":"Sarcopenia and Cognitive Impairment: A Systematic Review and Meta-Analysis","volume":"39","author":"Peng","year":"2020","journal-title":"Clin. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102540","DOI":"10.1016\/j.arr.2024.102540","article-title":"Immunosenescence and Inflammaging: Mechanisms and Role in Diseases","volume":"101","author":"Ajoolabady","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Jurc\u0103u, M.C., Andronie-Cioara, F.L., Jurc\u0103u, A., Marcu, F., \u0162i\u021b, D.M., Pa\u0219cal\u0103u, N., and Nistor-Cseppent\u00f6, D.C. (2022). The Link between Oxidative Stress, Mitochondrial Dysfunction and Neuroinflammation in the Pathophysiology of Alzheimer\u2019s Disease: Therapeutic Implications and Future Perspectives. Antioxidants, 11.","DOI":"10.3390\/antiox11112167"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/bs.ircmb.2018.05.006","article-title":"Mitochondria and Reactive Oxygen Species in Aging and Age-Related Diseases","volume":"340","author":"Giorgi","year":"2018","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/s41392-022-01251-0","article-title":"Aging and Aging-Related Diseases: From Molecular Mechanisms to Interventions and Treatments","volume":"7","author":"Guo","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s12979-020-0173-8","article-title":"Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging","volume":"17","author":"Thomas","year":"2020","journal-title":"Immun. Ageing"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e13671","DOI":"10.1111\/acel.13671","article-title":"Age-related Thymic Involution: Mechanisms and Functional Impact","volume":"21","author":"Liang","year":"2022","journal-title":"Aging Cell"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Fulop, T., Franceschi, C., Hirokawa, K., and Pawelec, G. (2009). Thymic Involution and Thymic Renewal. Handbook on Immunosenescence, Springer.","DOI":"10.1007\/978-1-4020-9063-9"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Mitchell, W.A., and Aspinall, R. (2007). Immunosenescence, Thymic Involution and Autoimmunity. Immunosenescence, Springer.","DOI":"10.1007\/978-0-387-76842-7_7"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tong, Q.-Y., Zhang, J.-C., Guo, J.-L., Li, Y., Yao, L.-Y., Wang, X., Yang, Y.-G., and Sun, L.-G. (2020). Human Thymic Involution and Aging in Humanized Mice. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01399"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.celrep.2018.01.015","article-title":"Age-Associated Decline in Thymic B Cell Expression of Aire and Aire-Dependent Self-Antigens","volume":"22","author":"Cepeda","year":"2018","journal-title":"Cell Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.autrev.2017.10.017","article-title":"Beyond APECED: An Update on the Role of the Autoimmune Regulator Gene (AIRE) in Physiology and Disease","volume":"17","author":"Conteduca","year":"2018","journal-title":"Autoimmun. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"21777","DOI":"10.18632\/oncotarget.4970","article-title":"Thymic Involution beyond T-Cell Insufficiency","volume":"6","author":"Coder","year":"2015","journal-title":"Oncotarget"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.1182\/blood-2008-04-149435","article-title":"Exogenous Insulin-like Growth Factor 1 Enhances Thymopoiesis Predominantly through Thymic Epithelial Cell Expansion","volume":"112","author":"Chu","year":"2008","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/ni.2193","article-title":"The Thymic Epithelial microRNA Network Elevates the Threshold for Infection-Associated Thymic Involution via miR-29a Mediated Suppression of the IFN-\u03b1 Receptor","volume":"13","author":"Papadopoulou","year":"2012","journal-title":"Nat. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1016\/j.ygeno.2020.11.031","article-title":"Comprehensive Analysis of lncRNAs, miRNAs and mRNAs Related to Thymic Development and Involution in Goose","volume":"113","author":"Li","year":"2021","journal-title":"Genomics"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Rezaei, N. (2020). Age-Related Thymic Atrophy: Mechanisms and Outcomes. Thymus, IntechOpen.","DOI":"10.5772\/intechopen.73777"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1002\/eji.201142305","article-title":"Molecular Control over Thymic Involution: From Cytokines and Micro RNA to Aging and Adipose Tissue","volume":"42","author":"Dooley","year":"2012","journal-title":"Eur. J. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Palmer, D.B. (2013). The Effect of Age on Thymic Function. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00316"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7986071","DOI":"10.1155\/2020\/7986071","article-title":"Implications of Oxidative Stress and Cellular Senescence in Age-Related Thymus Involution","volume":"2020","author":"Barbouti","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1093\/intimm\/dxh104","article-title":"Age-Related Thymic Involution Is Mediated by Fas on Thymic Epithelial Cells","volume":"16","author":"Yajima","year":"2004","journal-title":"Int. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.mad.2004.09.016","article-title":"Genetic Regulation of Thymic Involution","volume":"126","author":"Hsu","year":"2005","journal-title":"Mech. Ageing Dev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13148-021-01197-0","article-title":"Epigenetic Modifications in Thymic Epithelial Cells: An Evolutionary Perspective for Thymus Atrophy","volume":"13","author":"Hu","year":"2021","journal-title":"Clin. Epigenet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4073","DOI":"10.4049\/jimmunol.1500046","article-title":"Naive T Cell Maintenance and Function in Human Aging","volume":"194","author":"Goronzy","year":"2015","journal-title":"J. Immunol."},{"key":"ref_30","unstructured":"Fulop, T., Franceschi, C., Hirokawa, K., and Pawelec, G. (2018). Mechanisms of Naive CD4+ T Cell Maintenance in the Elderly and Its Implications for Autoimmunity. Handbook of Immunosenescence, Springer International Publishing."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.cmet.2022.11.005","article-title":"Age-Associated Remodeling of T Cell Immunity and Metabolism","volume":"35","author":"Han","year":"2023","journal-title":"Cell Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"784","DOI":"10.4049\/jimmunol.182.2.784","article-title":"Clonal Expansions and Loss of Receptor Diversity in the Naive CD8 T Cell Repertoire of Aged Mice","volume":"182","author":"Ahmed","year":"2009","journal-title":"J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"K\u00f6krek, E., and Pir, P. (2024). Distinct Deregulation Trends of Transcriptional Protein Complexes in Aging Naive T Cells. J. Leukoc. Biol., 117.","DOI":"10.1093\/jleuko\/qiae231"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1080\/08916930802024889","article-title":"The Role of Epigenetics in Aging and Autoimmunity","volume":"41","author":"Ray","year":"2008","journal-title":"Autoimmunity"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Jasiulionis, M.G. (2018). Abnormal Epigenetic Regulation of Immune System during Aging. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00197"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Callender, L.A., Carroll, E.C., Garrod-Ketchley, C., Schroth, J., Bystrom, J., Berryman, V., Pattrick, M., Campbell-Richards, D., Hood, G.A., and Hitman, G.A. (2021). Altered Nutrient Uptake Causes Mitochondrial Dysfunction in Senescent CD8+ EMRA T Cells During Type 2 Diabetes. Front. Aging, 2.","DOI":"10.3389\/fragi.2021.681428"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"864","DOI":"10.4093\/dmj.2024.0140","article-title":"T-Cell Senescence in Human Metabolic Diseases","volume":"48","author":"Nga","year":"2024","journal-title":"Diabetes Metab. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s10522-005-7955-4","article-title":"Age-Related Susceptibility of Naive and Memory CD4 T Cells to Apoptosis Induced by IL-2 Deprivation or PHA Addition","volume":"6","author":"Donnini","year":"2005","journal-title":"Biogerontology"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Verdon, D.J., Mulazzani, M., and Jenkins, M.R. (2020). Cellular and Molecular Mechanisms of CD8+ T Cell Differentiation, Dysfunction and Exhaustion. Int. J. Mol. Sci., 21.","DOI":"10.20944\/preprints202008.0728.v1"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nri3862","article-title":"Molecular and Cellular Insights into T Cell Exhaustion","volume":"15","author":"Wherry","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"SCI-38","DOI":"10.1182\/blood.V122.21.SCI-38.SCI-38","article-title":"Molecular Basis of T-Cell Exhaustion","volume":"122","author":"Wherry","year":"2013","journal-title":"Blood"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Saka, D., G\u00f6kalp, M., Piyade, B., Cevik, N.C., Arik Sever, E., Unutmaz, D., Ceyhan, G.O., Demir, I.E., and Asimgil, H. (2020). Mechanisms of T-Cell Exhaustion in Pancreatic Cancer. Cancers, 12.","DOI":"10.3390\/cancers12082274"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1747349","DOI":"10.1080\/2162402X.2020.1747349","article-title":"Receptor Signaling, Transcriptional, and Metabolic Regulation of T Cell Exhaustion","volume":"9","author":"Balkhi","year":"2020","journal-title":"OncoImmunology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"S384","DOI":"10.21037\/tcr.2017.03.02","article-title":"Unlocking the Epigenetic Code of T Cell Exhaustion","volume":"6","author":"Wu","year":"2017","journal-title":"Transl. Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/gerona\/glaa271","article-title":"Horticultural Therapy Reduces Biomarkers of Immunosenescence and Inflammaging in Community-Dwelling Older Adults: A Feasibility Pilot Randomized Controlled Trial","volume":"76","author":"Wong","year":"2021","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"111710","DOI":"10.1016\/j.mad.2022.111710","article-title":"Long-Term Caloric Restriction Ameliorates T Cell Immunosenescence in Mice","volume":"206","author":"Asami","year":"2022","journal-title":"Mech. Ageing Dev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/s41419-023-06146-8","article-title":"Hepatic T-Cell Senescence and Exhaustion Are Implicated in the Progression of Fatty Liver Disease in Patients with Type 2 Diabetes and Mouse Model with Nonalcoholic Steatohepatitis","volume":"14","author":"Sim","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1038\/leu.2016.84","article-title":"Multiple Myeloma Causes Clonal T-Cell Immunosenescence: Identification of Potential Novel Targets for Promoting Tumour Immunity and Implications for Checkpoint Blockade","volume":"30","author":"Suen","year":"2016","journal-title":"Leukemia"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"IA06","DOI":"10.1158\/2326-6066.IMM2016-IA06","article-title":"Abstract IA06: Molecular Basis of T Cell Exhaustion: Insights for Immunotherapy","volume":"4","author":"Wherry","year":"2016","journal-title":"Cancer Immunol. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e14300","DOI":"10.1111\/acel.14300","article-title":"Are Immunosenescent T Cells Really Senescent?","volume":"23","author":"Slaets","year":"2024","journal-title":"Aging Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"IA17","DOI":"10.1158\/2326-6074.TUMIMM18-IA17","article-title":"Abstract IA17: Molecular Mechanisms of T-Cell Exhaustion and Implications for Immunotherapy","volume":"8","author":"Wherry","year":"2020","journal-title":"Cancer Immunol. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"289","DOI":"10.2174\/157016211797636008","article-title":"HIV Infection-Related Premature Immunosenescence: High Rates of Immune Exhaustion After Short Time of Infection","volume":"9","author":"Viciana","year":"2011","journal-title":"Curr. HIV Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s00281-019-00744-5","article-title":"CD8+ T Cell Exhaustion","volume":"41","author":"Kurachi","year":"2019","journal-title":"Semin. Immunopathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"217","DOI":"10.5483\/BMBRep.2011.44.4.217","article-title":"Mechanism of T Cell Exhaustion in a Chronic Environment","volume":"44","author":"Jin","year":"2011","journal-title":"BMB Rep."},{"key":"ref_55","first-page":"609","article-title":"Molecular Profiles of Exhausted T Cells and Their Impact on Response to Immune Checkpoint Blockade","volume":"49","author":"Kagoya","year":"2022","journal-title":"Gan Kagaku Ryoho. Cancer Chemother."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Palatella, M., Guillaume, S.M., Linterman, M.A., and Huehn, J. (2022). The Dark Side of Tregs during Aging. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.940705"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5283","DOI":"10.4049\/jimmunol.180.8.5283","article-title":"Aging Down-Regulates the Transcription Factor E2A, Activation-Induced Cytidine Deaminase, and Ig Class Switch in Human B Cells","volume":"180","author":"Frasca","year":"2008","journal-title":"J. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"S120","DOI":"10.4049\/jimmunol.178.Supp.85.14","article-title":"Decreases in E2A, AID, and Ig Class Switch Show Intrinsic Defects in Human B Cells with Age (85.14)","volume":"178","author":"Blomberg","year":"2007","journal-title":"J. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.smim.2005.05.005","article-title":"Humoral Immune Response and B-Cell Functions Including Immunoglobulin Class Switch Are Downregulated in Aged Mice and Humans","volume":"17","author":"Frasca","year":"2005","journal-title":"Semin. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"34.5","DOI":"10.4049\/jimmunol.182.Supp.34.5","article-title":"Reduced Response to Influenza Vaccine Associates with Reduced AID in Aged Human B Lymphocytes (34.5)","volume":"182","author":"Blomberg","year":"2009","journal-title":"J. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.4049\/jimmunol.1000698","article-title":"Deletion of IgG-Switched Autoreactive B Cells and Defects in Faslpr Lupus Mice","volume":"185","author":"Kono","year":"2010","journal-title":"J. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1159\/000504479","article-title":"Age-Related Changes in B Cells Relevant to Vaccine Responses","volume":"Volume 43","author":"Weinberger","year":"2020","journal-title":"Interdisciplinary Topics in Gerontology and Geriatrics"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1002\/eji.201646446","article-title":"Scarcity of Autoreactive Human Blood IgA+ Memory B Cells","volume":"46","author":"Prigent","year":"2016","journal-title":"Eur. J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"218.3","DOI":"10.4049\/jimmunol.204.Supp.218.3","article-title":"Autoreactive B Cells Have a Specific Metabolic Response during Humoral Responses","volume":"204","author":"Choi","year":"2020","journal-title":"J. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s12979-019-0164-9","article-title":"Immunosenescence and Human Vaccine Immune Responses","volume":"16","author":"Crooke","year":"2019","journal-title":"Immun. Ageing"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s10522-009-9256-9","article-title":"The Ageing B Cell Population: Composition and Function","volume":"11","author":"Ademokun","year":"2010","journal-title":"Biogerontology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1182\/blood-2010-03-275859","article-title":"High-Throughput Immunoglobulin Repertoire Analysis Distinguishes between Human IgM Memory and Switched Memory B-Cell Populations","volume":"116","author":"Wu","year":"2010","journal-title":"Blood"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.coi.2010.05.003","article-title":"Aging of the Innate Immune System","volume":"22","author":"Shaw","year":"2010","journal-title":"Curr. Opin. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e66703","DOI":"10.7554\/eLife.66703","article-title":"Loss of Mir146b with Aging Contributes to Inflammation and Mitochondrial Dysfunction in Thioglycollate-Elicited Peritoneal Macrophages","volume":"10","author":"Santeford","year":"2021","journal-title":"eLife"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"114073","DOI":"10.1016\/j.celrep.2024.114073","article-title":"Aging-Related Defects in Macrophage Function Are Driven by MYC and USF1 Transcriptional Programs","volume":"43","author":"Moss","year":"2024","journal-title":"Cell Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"442","DOI":"10.37349\/ei.2023.00112","article-title":"Mitochondrial Dysfunction at the Cornerstone of Inflammatory Exacerbation in Aged Macrophages","volume":"3","author":"Maurmann","year":"2023","journal-title":"Explor. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e200026","DOI":"10.20900\/immunometab20200026","article-title":"Macrophage Immunometabolism and Inflammaging: Roles of Mitochondrial Dysfunction, Cellular Senescence, CD38, and NAD","volume":"2","author":"Yarbro","year":"2020","journal-title":"Immunometabolism"},{"key":"ref_73","first-page":"e120157","article-title":"Macrophage microRNA-150 Promotes Pathological Angiogenesis as Seen in Age-Related Macular Degeneration","volume":"3","author":"Lin","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/s41590-021-01083-0","article-title":"Aging Disrupts Circadian Gene Regulation and Function in Macrophages","volume":"23","author":"Blacher","year":"2022","journal-title":"Nat. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41577-021-00674-0","article-title":"A Broken Immune Clock in Old Macrophages","volume":"22","author":"Bordon","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1159\/000370112","article-title":"Autophagy Controls Acquisition of Aging Features in Macrophages","volume":"7","author":"Stranks","year":"2015","journal-title":"J. Innate Immun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.bbrc.2020.05.121","article-title":"Age-Related Dysfunction of P53-Regulated Phagocytic Activity in Macrophages","volume":"529","author":"Yamaguchi","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.it.2009.05.004","article-title":"Human Innate Immunosenescence: Causes and Consequences for Immunity in Old Age","volume":"30","author":"Panda","year":"2009","journal-title":"Trends Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Fulop, T., Franceschi, C., Hirokawa, K., and Pawelec, G. (2009). Molecular and Cellular Aspects of Macrophage Aging. Handbook on Immunosenescence, Springer.","DOI":"10.1007\/978-1-4020-9063-9"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1136\/gutjnl-2016-312940","article-title":"Age-Dependent Shift in Macrophage Polarization Causes Inflammation Mediated Degeneration of Enteric Nervous System","volume":"67","author":"Becker","year":"2018","journal-title":"Gut"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1189\/jlb.1103592","article-title":"Aging and Innate Immune Cells","volume":"76","author":"Plackett","year":"2004","journal-title":"J. Leukoc. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1046\/j.1365-2567.2000.00079.x","article-title":"Ageing and the Neutrophil: No Appetite for Killing?","volume":"100","author":"Butcher","year":"2000","journal-title":"Immunology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1007\/s10753-017-0725-z","article-title":"Changes in Neutrophil Metabolism upon Activation and Aging","volume":"41","author":"Richer","year":"2018","journal-title":"Inflammation"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.it.2016.03.005","article-title":"Aging: A Temporal Dimension for Neutrophils","volume":"37","author":"Adrover","year":"2016","journal-title":"Trends Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1100\/TSW.2001.105","article-title":"Functional Decline in Human Neutrophils with Age","volume":"1","author":"Butcher","year":"2001","journal-title":"Sci. World J."},{"key":"ref_86","first-page":"245","article-title":"Effects of age on activation of human neutrophils","volume":"36","author":"Ito","year":"1996","journal-title":"J. Jpn. Soc. Reticuloendothel. Syst."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"M169","DOI":"10.1093\/gerona\/53A.3.M169","article-title":"Impaired Glutathione Peroxidase Activity Accounts for the Age-Related Accumulation of Hydrogen Peroxide in Activated Human Neutrophils","volume":"53A","author":"Ito","year":"1998","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1134\/S0022093021030017","article-title":"Molecular Mechanisms for Regulationof Neutrophil Apoptosis under Normal and Pathological Conditions","volume":"57","author":"Noseykina","year":"2021","journal-title":"J. Evol. Biochem. Phys."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.coi.2014.03.009","article-title":"Expanding Roles of Neutrophils in Aging Hosts","volume":"29","author":"Tseng","year":"2014","journal-title":"Curr. Opin. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.cjtee.2022.06.002","article-title":"Recent Advances in Neutrophil Chemotaxis Abnormalities during Sepsis","volume":"25","author":"Zhou","year":"2022","journal-title":"Chin. J. Traumatol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s11357-015-9828-3","article-title":"Effects of Aging on Human Leukocytes (Part I): Immunophenotyping of Innate Immune Cells","volume":"37","author":"Stervbo","year":"2015","journal-title":"Age"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"121","DOI":"10.2174\/1876326X01206010121","article-title":"The Innate Immune System and Aging: What Is the Contribution to Immunosenescence ?","volume":"6","author":"Fulop","year":"2012","journal-title":"Open Longev. Sci."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Grifoni, A., Alonzi, T., Alter, G., Noonan, D.M., Landay, A.L., Albini, A., and Goletti, D. (2023). Impact of Aging on Immunity in the Context of COVID-19, HIV, and Tuberculosis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1146704"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Camous, X., Pera, A., Solana, R., and Larbi, A. (2012). NK Cells in Healthy Aging and Age-Associated Diseases. J. Biomed. Biotechnol., 2012.","DOI":"10.1155\/2012\/195956"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1006\/cimm.1996.0271","article-title":"Involvement of Cytokine Gene Expression in the Age-Dependent Decline of NK Cell Response","volume":"173","author":"Hsueh","year":"1996","journal-title":"Cell. Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"4688","DOI":"10.4049\/jimmunol.1301625","article-title":"The Host Environment Is Responsible for Aging-Related Functional NK Cell Deficiency","volume":"191","author":"Chiu","year":"2013","journal-title":"J. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S1873-9598(08)70025-5","article-title":"NK\/NKT Cells and Aging","volume":"1","author":"Chen","year":"2007","journal-title":"Int. J. Gerontol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.coi.2014.04.002","article-title":"Shaping of NK Cell Subsets by Aging","volume":"29","author":"Solana","year":"2014","journal-title":"Curr. Opin. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"7871814","DOI":"10.1155\/2018\/7871814","article-title":"Effect of Aging on NK Cell Population and Their Proliferation at Ex Vivo Culture Condition","volume":"2018","author":"Gounder","year":"2018","journal-title":"Anal. Cell. Pathol."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Brauning, A., Rae, M., Zhu, G., Fulton, E., Admasu, T.D., Stolzing, A., and Sharma, A. (2022). Aging of the Immune System: Focus on Natural Killer Cells Phenotype and Functions. Cells, 11.","DOI":"10.3390\/cells11061017"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3565127","DOI":"10.1155\/2016\/3565127","article-title":"ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases","volume":"2016","author":"Davalli","year":"2016","journal-title":"Oxidative Med. Cell Longev."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2891","DOI":"10.4049\/jimmunol.1600590","article-title":"Killer Cell Lectin-like Receptor G1 Inhibits NK Cell Function through Activation of Adenosine 5\u2032-Monophosphate-Activated Protein Kinase","volume":"197","author":"Lanna","year":"2016","journal-title":"J. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1474-9728.2004.00107.x","article-title":"NK and NKT Cell Functions in Immunosenescence","volume":"3","author":"Mocchegiani","year":"2004","journal-title":"Aging Cell"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.smim.2012.04.008","article-title":"Innate Immunosenescence: Effect of Aging on Cells and Receptors of the Innate Immune System in Humans","volume":"24","author":"Solana","year":"2012","journal-title":"Semin. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/s41577-021-00558-3","article-title":"Natural Killer Cells in Antiviral Immunity","volume":"22","author":"Strunz","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Pereira, B.I., and Akbar, A.N. (2016). Convergence of Innate and Adaptive Immunity during Human Aging. Front. Immunol., 7.","DOI":"10.3389\/fimmu.2016.00445"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"419","DOI":"10.15789\/1563-0625-IAT-1938","article-title":"Inflammaging as the Basis of Age-Associated Diseases","volume":"22","author":"Artemyeva","year":"2020","journal-title":"Med. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/s41569-018-0064-2","article-title":"Inflammageing: Chronic Inflammation in Ageing, Cardiovascular Disease, and Frailty","volume":"15","author":"Ferrucci","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_109","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_110","doi-asserted-by":"crossref","unstructured":"Rea, I.M., Gibson, D.S., McGilligan, V., McNerlan, S.E., Alexander, H.D., and Ross, O.A. (2018). Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00586"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e158448","DOI":"10.1172\/JCI158448","article-title":"Connecting Aging Biology and Inflammation in the Omics Era","volume":"132","author":"Walker","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_112","first-page":"177","article-title":"Zapalenie Starcze\u2014Mechanizmy i Szlaki Sygna\u0142owe","volume":"67","author":"Grabowska","year":"2021","journal-title":"Postep. Biochem."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Dom\u00ednguez, M. (2025). Pathological and Inflammatory Consequences of Aging. Biomolecules, 15.","DOI":"10.3390\/biom15030404"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1810327","DOI":"10.1155\/2016\/1810327","article-title":"\u201cInflammaging\u201d as a Druggable Target: A Senescence-Associated Secretory Phenotype\u2014Centered View of Type 2 Diabetes","volume":"2016","author":"Prattichizzo","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1093\/jb\/mvz055","article-title":"Deciphering the Mechanism for Induction of Senescence-Associated Secretory Phenotype (SASP) and Its Role in Ageing and Cancer Development","volume":"166","author":"Ohtani","year":"2019","journal-title":"J. Biochem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1093\/jb\/mvaa109","article-title":"Senescence-Associated Extracellular Vesicle Release Plays a Role in Senescence-Associated Secretory Phenotype (SASP) in Age-Associated Diseases","volume":"169","author":"Tanaka","year":"2021","journal-title":"J. Biochem."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Sebastian-Valverde, M., and Pasinetti, G.M. (2020). The NLRP3 Inflammasome as a Critical Actor in the Inflammaging Process. Cells, 9.","DOI":"10.3390\/cells9061552"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"100102","DOI":"10.1016\/j.glmedi.2024.100102","article-title":"Cholesterol Crystal Embolism: Unraveling Its Impact on Atherosclerotic Cardiovascular Diseases","volume":"3","author":"Waitupu","year":"2024","journal-title":"J. Med. Surg. Public Health"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"30","DOI":"10.26480\/msm.01.2017.30.33","article-title":"Aging Mechanisms: Linking Oxidative Stress, Obesity and Inflammation","volume":"1","author":"Abbas","year":"2017","journal-title":"Matrix Sci. Medica"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s41392-023-01502-8","article-title":"Inflammation and Aging: Signaling Pathways and Intervention Therapies","volume":"8","author":"Li","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.arr.2007.09.002","article-title":"Activation of Innate Immunity System during Aging: NF-kB Signaling Is the Molecular Culprit of Inflamm-Aging","volume":"7","author":"Salminen","year":"2008","journal-title":"Ageing Res. Rev."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Yang, Y., Liu, Y., Wang, Y., Chao, Y., Zhang, J., Jia, Y., Tie, J., and Hu, D. (2022). Regulation of SIRT1 and Its Roles in Inflammation. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.831168"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/j.arr.2013.05.001","article-title":"MicroRNAs Linking Inflamm-Aging, Cellular Senescence and Cancer","volume":"12","author":"Olivieri","year":"2013","journal-title":"Ageing Res. Rev."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.exger.2008.12.005","article-title":"Atypical Pathways of NF-kappaB Activation and Aging","volume":"44","author":"Kriete","year":"2009","journal-title":"Exp. Gerontol."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Kim, M.E., and Lee, J.S. (2023). Immune Diseases Associated with Aging: Molecular Mechanisms and Treatment Strategies. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242115584"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1093\/abbs\/gmy088","article-title":"mTOR Regulates NLRP3 Inflammasome Activation via Reactive Oxygen Species in Murine Lupus","volume":"50","author":"Li","year":"2018","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Dai, J., Jiang, C., Chen, H., and Chai, Y. (2019). Rapamycin Attenuates High Glucose-Induced Inflammation Through Modulation of mTOR\/NF-\u03baB Pathways in Macrophages. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01292"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1093\/gerona\/glv078","article-title":"The Expression Changes of Inflammasomes in the Aging Rat Kidneys","volume":"71","author":"Song","year":"2016","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2999","DOI":"10.1007\/s00018-012-0962-0","article-title":"Mitochondrial Dysfunction and Oxidative Stress Activate Inflammasomes: Impact on the Aging Process and Age-Related Diseases","volume":"69","author":"Salminen","year":"2012","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1159\/000358901","article-title":"Oxidative Stress, Mitochondrial Dysfunction and the Mitochondria Theory of Aging","volume":"Volume 39","author":"Robert","year":"2014","journal-title":"Interdisciplinary Topics in Gerontology and Geriatrics"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.exger.2007.10.001","article-title":"The Role of Mitochondrial DNA Mutations in Aging and Sarcopenia: Implications for the Mitochondrial Vicious Cycle Theory of Aging","volume":"43","author":"Hiona","year":"2008","journal-title":"Exp. Gerontol."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Marcinek, D.J. (2015). Mitochondrial Oxidative Stress in Skeletal Muscle and Cardiac Aging. Free. Radic. Biol. Med., 86.","DOI":"10.1016\/j.freeradbiomed.2015.07.062"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1038\/s41590-020-0725-2","article-title":"Impaired Mitochondrial Oxidative Phosphorylation Limits the Self-Renewal of T Cells Exposed to Persistent Antigen","volume":"21","author":"Vardhana","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.lfs.2018.12.029","article-title":"Crosstalk between Mitochondrial Dysfunction, Oxidative Stress, and Age Related Neurodegenerative Disease: Etiologies and Therapeutic Strategies","volume":"218","author":"Elfawy","year":"2019","journal-title":"Life Sci."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"e13622","DOI":"10.1111\/acel.13622","article-title":"Defective Mitophagy in Aged Macrophages Promotes Mitochondrial DNA Cytosolic Leakage to Activate STING Signaling during Liver Sterile Inflammation","volume":"21","author":"Zhong","year":"2022","journal-title":"Aging Cell"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"De Gaetano, A., Gibellini, L., Zanini, G., Nasi, M., Cossarizza, A., and Pinti, M. (2021). Mitophagy and Oxidative Stress: The Role of Aging. Antioxidants, 10.","DOI":"10.3390\/antiox10050794"},{"key":"ref_137","first-page":"242","article-title":"Mitochondrial Dysfunction during Brain Aging: Role of Oxidative Stress and Modulation by Antioxidant Supplementation","volume":"2","author":"Chakrabarti","year":"2011","journal-title":"Aging Dis"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"8575263","DOI":"10.1155\/2018\/8575263","article-title":"The Effect of MitoQ on Aging-Related Biomarkers: A Systematic Review and Meta-Analysis","volume":"2018","author":"Braakhuis","year":"2018","journal-title":"Oxidative Med. Cell Longev."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"35","DOI":"10.20514\/2226-6704-2022-12-1-35-44","article-title":"Regulation of the Immune System in Aging: Focus on Epigenetic Mechanisms","volume":"12","author":"Aitbaev","year":"2022","journal-title":"Arh. Vnutr. Med."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/imr.13034","article-title":"Transcriptional and Epigenetic Regulation in Thymic Epithelial Cells","volume":"305","author":"Bhandoola","year":"2022","journal-title":"Immunol. Rev."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/s41392-021-00646-9","article-title":"Inflammation, Epigenetics, and Metabolism Converge to Cell Senescence and Ageing: The Regulation and Intervention","volume":"6","author":"Zhu","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Gomez-Verjan, J.C., and Rivero-Segura, N.A. (2020). Epigenetics and Ageing. Clinical Genetics and Genomics of Aging, Springer International Publishing.","DOI":"10.1007\/978-3-030-40955-5"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s00018-017-2596-8","article-title":"Orchestration of H3K27 Methylation: Mechanisms and Therapeutic Implication","volume":"75","author":"Pan","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_144","first-page":"81","article-title":"Epigenetics: Linking Nutrition to Molecular Mechanisms in Aging","volume":"22","author":"Park","year":"2017","journal-title":"Prev. Nutr. Food Sci."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"101755","DOI":"10.1016\/j.molmet.2023.101755","article-title":"Chronic Inflammation and the Hallmarks of Aging","volume":"74","author":"Baechle","year":"2023","journal-title":"Mol. Metab."},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Massoud, A., and Rezaei, N. (2014). A Role for Epigenetic Modulation of the Innate Immune Response During Aging. Immunology of Aging, Springer.","DOI":"10.1007\/978-3-642-39495-9"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/agm2.12030","article-title":"Role of lncRNAs in Aging and Age-related Diseases","volume":"1","author":"He","year":"2018","journal-title":"Aging Med."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Bhat, S.A., Sureshbabu, S.K., Philip, C.S., and Chiplunkar, S. (2020). Impact of Epigenetic Modifiers on the Immune System. Epigenetics of the Immune System, Elsevier.","DOI":"10.1016\/B978-0-12-817964-2.00014-9"},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Perlmutter, A., Bland, J.S., Chandra, A., Malani, S.S., Smith, R., Mendez, T.L., and Dwaraka, V.B. (2024). The Impact of a Polyphenol-Rich Supplement on Epigenetic and Cellular Markers of Immune Age: A Pilot Clinical Study. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1474597"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1438686","DOI":"10.1155\/2016\/1438686","article-title":"MicroRNA-Regulated Proinflammatory Cytokines in Sarcopenia","volume":"2016","author":"Fan","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Merchant, R.A., Chan, Y.H., Anbarasan, D., and Vellas, B. (2024). Association of Intrinsic Capacity with Functional Ability, Sarcopenia and Systemic Inflammation in Pre-Frail Older Adults. Front. Med., 11.","DOI":"10.3389\/fmed.2024.1374197"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.arr.2017.01.006","article-title":"Frailty and Sarcopenia: The Potential Role of an Aged Immune System","volume":"36","author":"Wilson","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1038\/s41430-024-01486-w","article-title":"The Association between Inflammatory Cytokines and Sarcopenia-Related Traits: A Bi-Directional Mendelian Randomization Study","volume":"78","author":"Wang","year":"2024","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"526.e9\u2013526.e17","DOI":"10.1016\/j.amjmed.2005.10.049","article-title":"Inflammatory Markers and Loss of Muscle Mass (Sarcopenia) and Strength","volume":"119","author":"Schaap","year":"2006","journal-title":"Am. J. Med."},{"key":"ref_155","first-page":"191","article-title":"Why Age Matters: Inflammation, Cancer and Hormones in the Development of Sarcopenia","volume":"5","author":"Saul","year":"2017","journal-title":"J. Osteopor. Phys. Act."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"23497","DOI":"10.18632\/aging.202200","article-title":"Pharmacological Blockade of TNF\u03b1 Prevents Sarcopenia and Prolongs Survival in Aging Mice","volume":"12","author":"Sciorati","year":"2020","journal-title":"Aging"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1143.7","DOI":"10.1096\/fasebj.26.1_supplement.1143.7","article-title":"Aging, Inflammation and Skeletal Muscle","volume":"26","author":"White","year":"2012","journal-title":"FASEB J."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1136\/annrheumdis-2022-eular.4571","article-title":"POS1446 Creatine Kinase Could be a Marker of Chronic Inflammation-Induced Sarcopenia in Frail Patients","volume":"81","author":"Bermejo","year":"2022","journal-title":"Ann. Rheum. Dis."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Cui, C.-Y., Ferrucci, L., and Gorospe, M. (2023). Macrophage Involvement in Aging-Associated Skeletal Muscle Regeneration. Cells, 12.","DOI":"10.3390\/cells12091214"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Ryu, J.Y., Choi, H.M., Yang, H.-I., and Kim, K.S. (2020). Dysregulated Autophagy Mediates Sarcopenic Obesity and Its Complications via AMPK and PGC1\u03b1 Signaling Pathways: Potential Involvement of Gut Dysbiosis as a Pathological Link. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186887"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1515\/revneuro-2022-0087","article-title":"Dysfunctional Microglia and Tau Pathology in Alzheimer\u2019s Disease","volume":"34","author":"Ayyubova","year":"2023","journal-title":"Rev. Neurosci."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"4010","DOI":"10.1021\/acschemneuro.4c00370","article-title":"Propionate Decreases Microglial Activation but Impairs Phagocytic Capacity in Response to Aggregated Fibrillar Amyloid Beta Protein","volume":"15","author":"Gold","year":"2024","journal-title":"ACS Chem. Neurosci."},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Vogt, N.M., Kerby, R.L., Dill-McFarland, K.A., Harding, S.J., Merluzzi, A.P., Johnson, S.C., Carlsson, C.M., Asthana, S., Zetterberg, H., and Blennow, K. (2017). Gut Microbiome Alterations in Alzheimer\u2019s Disease. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-13601-y"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"110837","DOI":"10.1016\/j.exger.2020.110837","article-title":"Inflammatory Markers Associated with Fall Recurrence and Severity: The Bambu\u00ed Cohort Study of Aging","volume":"132","author":"Torres","year":"2020","journal-title":"Exp. Gerontol."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Sugahara, H., Okai, S., Odamaki, T., Wong, C.B., Kato, K., Mitsuyama, E., Xiao, J.-Z., and Shinkura, R. (2017). Decreased Taxon-Specific IgA Response in Relation to the Changes of Gut Microbiota Composition in the Elderly. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.01757"},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Whelan, S., Lucey, B., and Finn, K. (2023). Uropathogenic Escherichia Coli (UPEC)-Associated Urinary Tract Infections: The Molecular Basis for Challenges to Effective Treatment. Microorganisms, 11.","DOI":"10.3390\/microorganisms11092169"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"100938","DOI":"10.1016\/j.arr.2019.100938","article-title":"Intestinal Epithelial Barrier Functions in Ageing","volume":"54","author":"Branca","year":"2019","journal-title":"Ageing Res. Rev."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1212\/01.wnl.0000338622.27876.0d","article-title":"Microglial Activation and Amyloid Deposition in Mild Cognitive Impairment: A PET Study","volume":"72","author":"Okello","year":"2009","journal-title":"Neurology"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"e061720","DOI":"10.1002\/alz.061720","article-title":"Natural Killer Cells Improve Cognitive Function and Support to Induce Amyloid Beta Clearance by Functional Recovery of Impaired Microglia in Natural Killer Cell-treated Alzheimer\u2019s Diseases Mouse Model","volume":"18","author":"Hwang","year":"2022","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Cai, Y., Liu, J., Wang, B., Sun, M., and Yang, H. (2022). Microglia in the Neuroinflammatory Pathogenesis of Alzheimer\u2019s Disease and Related Therapeutic Targets. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.856376"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"e101064","DOI":"10.15252\/embj.2018101064","article-title":"Systemic Inflammation Impairs Microglial A\u03b2 Clearance through NLRP3 Inflammasome","volume":"38","author":"Tejera","year":"2019","journal-title":"EMBO J."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.pnpbp.2017.05.007","article-title":"Molecular Imaging of Neuroinflammation in Alzheimer\u2019s Disease and Mild Cognitive Impairment","volume":"80","author":"Knezevic","year":"2018","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1111\/ejn.15914","article-title":"TREM2 Signalling as a Multifaceted Player in Brain Homoeostasis and a Potential Target for Alzheimer\u2019s Disease Treatment","volume":"57","author":"Ayyubova","year":"2023","journal-title":"Eur. J. Neurosci."},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Huang, W., Huang, J., Huang, N., and Luo, Y. (2023). The Role of TREM2 in Alzheimer\u2019s Disease: From the Perspective of Tau. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1280257"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41392-024-01743-1","article-title":"Microbiota\u2013Gut\u2013Brain Axis and Its Therapeutic Applications in Neurodegenerative Diseases","volume":"9","author":"Loh","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"e70091","DOI":"10.1111\/cns.70091","article-title":"The Gut Microbiota Modulates Neuroinflammation in Alzheimer\u2019s Disease: Elucidating Crucial Factors and Mechanistic Underpinnings","volume":"30","author":"Yang","year":"2024","journal-title":"CNS Neurosci. Ther."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/bs.abger.2024.05.005","article-title":"Chapter Five\u2014Role of Immunosenescence in Impaired Wound Healing with Age","volume":"Volume 2","author":"Atayik","year":"2024","journal-title":"Advances in Biogerontology"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.4049\/jimmunol.1201213","article-title":"Reduced Neutrophil Chemotaxis and Infiltration Contributes to Delayed Resolution of Cutaneous Wound Infection with Advanced Age","volume":"190","author":"Brubaker","year":"2013","journal-title":"J. Immunol."},{"key":"ref_179","first-page":"897","article-title":"Immune regulation of wound healing","volume":"70","author":"Becker","year":"1999","journal-title":"Der Chir."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1089\/wound.2011.0307","article-title":"Regulation of Macrophage Polarization and Wound Healing","volume":"1","author":"Ferrante","year":"2012","journal-title":"Adv. Wound Care"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"181.3","DOI":"10.1096\/fasebj.24.1_supplement.181.3","article-title":"Impact of Aging on Dermal Wound Healing","volume":"24","author":"Brubaker","year":"2010","journal-title":"FASEB J."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s00586-019-06168-x","article-title":"Inflammatory Mediators and the Risk of Falls among Older Women with Acute Low Back Pain: Data from Back Complaints in the Elders (BACE)\u2014Brazil","volume":"29","author":"Pereira","year":"2020","journal-title":"Eur. Spine J."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1002\/JLB.3RI0620-405RR","article-title":"Age-Related Changes in Intestinal Immunity and the Microbiome","volume":"109","author":"Walrath","year":"2021","journal-title":"J. Leukoc. Biol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"e13700","DOI":"10.1111\/acel.13700","article-title":"A Gut-Centric View of Aging: Do Intestinal Epithelial Cells Contribute to Age-Associated Microbiota Changes, Inflammaging, and Immunosenescence?","volume":"21","author":"Hohman","year":"2022","journal-title":"Aging Cell"},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Zheng, H., Zhang, C., Wang, Q., Feng, S., Fang, Y., and Zhang, S. (2022). The Impact of Aging on Intestinal Mucosal Immune Function and Clinical Applications. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1029948"},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Ru\u021ba, F., Pribac, M., Mardale, E., Suciu, S., Maior, R., Bogdan, S., and Avram, C. (2024). Associations between Gut Microbiota Dysbiosis and Other Risk Factors in Women with a History of Urinary Tract Infections. Nutrients, 16.","DOI":"10.3390\/nu16111753"},{"key":"ref_187","doi-asserted-by":"crossref","unstructured":"Iqbal, Z.S., Halkj\u00e6r, S.I., Ghathian, K.S.A., Heintz, J.E., and Petersen, A.M. (2024). The Role of the Gut Microbiome in Urinary Tract Infections: A Narrative Review. Nutrients, 16.","DOI":"10.3390\/nu16213615"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.aninu.2021.09.012","article-title":"The Interaction among Gut Microbes, the Intestinal Barrier and Short Chain Fatty Acids","volume":"9","author":"Ma","year":"2022","journal-title":"Anim. Nutr."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.cger.2020.08.006","article-title":"Fecal Incontinence in the Elderly","volume":"37","author":"Pasricha","year":"2021","journal-title":"Clin. Geriatr. Med."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"iqad004","DOI":"10.1093\/oxfimm\/iqad004","article-title":"The Ageing Immune System as a Potential Target of Senolytics","volume":"4","author":"Du","year":"2023","journal-title":"Oxf. Open Immunol."},{"key":"ref_191","doi-asserted-by":"crossref","unstructured":"Ribeiro, H., Rodrigues, I., Napole\u00e3o, L., Lira, L., Marques, D., Ver\u00edssimo, M., Andrade, J.P., and Dourado, M. (2022). Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), Pain and Aging: Adjusting Prescription to Patient Features. Biomed. Pharmacother., 150.","DOI":"10.1016\/j.biopha.2022.112958"},{"key":"ref_192","doi-asserted-by":"crossref","unstructured":"Sorrenti, V., Benedetti, F., Buriani, A., Fortinguerra, S., Caudullo, G., Davinelli, S., Zella, D., and Scapagnini, G. (2022). Immunomodulatory and Antiaging Mechanisms of Resveratrol, Rapamycin, and Metformin: Focus on mTOR and AMPK Signaling Networks. Pharmaceuticals, 15.","DOI":"10.3390\/ph15080912"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/s43587-023-00560-5","article-title":"Prophylactic and Long-Lasting Efficacy of Senolytic CAR T Cells against Age-Related Metabolic Dysfunction","volume":"4","author":"Amor","year":"2024","journal-title":"Nat. Aging"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"e13767","DOI":"10.1111\/acel.13767","article-title":"Senolytic Drugs, Dasatinib and Quercetin, Attenuate Adipose Tissue Inflammation, and Ameliorate Metabolic Function in Old Age","volume":"22","author":"Islam","year":"2023","journal-title":"Aging Cell"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"e907","DOI":"10.20883\/medical.e907","article-title":"Senescent Cells as New Pharmacological Targets for Age-Related Diseases and Anti-Aging Therapy","volume":"92","author":"Masternak","year":"2023","journal-title":"J. Med. Sci."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1111\/joim.13141","article-title":"Senolytic Drugs: From Discovery to Translation","volume":"288","author":"Kirkland","year":"2020","journal-title":"J. Intern. Med."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1146\/annurev-pharmtox-050120-105018","article-title":"Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span","volume":"61","author":"Robbins","year":"2021","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_198","doi-asserted-by":"crossref","unstructured":"Nambiar, A., Kellogg, D., Justice, J., Goros, M., Gelfond, J., Pascual, R., Hashmi, S., Masternak, M., Prata, L., and LeBrasseur, N. (2023). Senolytics Dasatinib and Quercetin in Idiopathic Pulmonary Fibrosis: Results of a Phase I, Single-Blind, Single-Center, Randomized, Placebo-Controlled Pilot Trial on Feasibility and Tolerability. eBioMedicine, 90.","DOI":"10.1016\/j.ebiom.2023.104481"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ebiom.2018.09.015","article-title":"Fisetin Is a Senotherapeutic That Extends Health and Lifespan","volume":"36","author":"Yousefzadeh","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"111995","DOI":"10.1016\/j.mad.2024.111995","article-title":"Fisetin as a Senotherapeutic Agent: Evidence and Perspectives for Age-Related Diseases","volume":"222","author":"Tavenier","year":"2024","journal-title":"Mech. Ageing Dev."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/acel.12445","article-title":"Identification of a Novel Senolytic Agent, Navitoclax, Targeting the Bcl-2 Family of Anti-Apoptotic Factors","volume":"15","author":"Zhu","year":"2016","journal-title":"Aging Cell"},{"key":"ref_202","doi-asserted-by":"crossref","unstructured":"Sharma, A.K., Roberts, R.L., Benson, R.D., Pierce, J.L., Yu, K., Hamrick, M.W., and McGee-Lawrence, M.E. (2020). The Senolytic Drug Navitoclax (ABT-263) Causes Trabecular Bone Loss and Impaired Osteoprogenitor Function in Aged Mice. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00354"},{"key":"ref_203","doi-asserted-by":"crossref","unstructured":"Carpenter, V.J., Saleh, T., and Gewirtz, D.A. (2021). Senolytics for Cancer Therapy: Is All That Glitters Really Gold?. Cancers, 13.","DOI":"10.3390\/cancers13040723"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"ehaa946.3746","DOI":"10.1093\/ehjci\/ehaa946.3746","article-title":"A Novel Senolytic Drug, Seno-7284 Ameliorates Aging Phenotype and Age-Related Cardiometabolic Diseases","volume":"41","author":"Katsuumi","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_205","doi-asserted-by":"crossref","unstructured":"Hassan, J.W., and Bhatwadekar, A.D. (2022). Senolytics in the Treatment of Diabetic Retinopathy. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.896907"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"3445","DOI":"10.1038\/s41467-023-39120-1","article-title":"Discovery of Senolytics Using Machine Learning","volume":"14","author":"Quintanilla","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_207","doi-asserted-by":"crossref","unstructured":"Lorenzo, E.C., Torrance, B.L., and Haynes, L. (2023). Impact of Senolytic Treatment on Immunity, Aging, and Disease. Front. Aging, 4.","DOI":"10.3389\/fragi.2023.1161799"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"e36483","DOI":"10.1016\/j.heliyon.2024.e36483","article-title":"Navitoclax Safety, Tolerability, and Effect on Biomarkers of Senescence and Neurodegeneration in Aged Nonhuman Primates","volume":"10","author":"Greenberg","year":"2024","journal-title":"Heliyon"},{"key":"ref_209","doi-asserted-by":"crossref","unstructured":"L\u2019H\u00f4te, V., Mann, C., and Thuret, J.-Y. (2022). From the Divergence of Senescent Cell Fates to Mechanisms and Selectivity of Senolytic Drugs. Open Biol., 12.","DOI":"10.1098\/rsob.220171"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"e75492","DOI":"10.7554\/eLife.75492","article-title":"Short Senolytic or Senostatic Interventions Rescue Progression of Radiation-Induced Frailty and Premature Ageing in Mice","volume":"11","author":"Fielder","year":"2022","journal-title":"eLife"},{"key":"ref_211","doi-asserted-by":"crossref","unstructured":"Murray, K.O., Mahoney, S.A., Ludwig, K.R., Miyamoto-Ditmon, J.H., VanDongen, N.S., Banskota, N., Herman, A.B., Seals, D.R., Mankowski, R.T., and Rossman, M.J. (2025). Intermittent Supplementation With Fisetin Improves Physical Function and Decreases Cellular Senescence in Skeletal Muscle With Aging: A Comparison to Genetic Clearance of Senescent Cells and Synthetic Senolytic Approaches. Aging Cell, e70114.","DOI":"10.1111\/acel.70114"},{"key":"ref_212","doi-asserted-by":"crossref","unstructured":"Ota, H., and Kodama, A. (2022). Dasatinib plus Quercetin Attenuates Some Frailty Characteristics in SAMP10 Mice. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-06448-5"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1002\/jcsm.13112","article-title":"The Impact of Senescence on Muscle Wasting in Chronic Kidney Disease","volume":"14","author":"Huang","year":"2023","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_214","doi-asserted-by":"crossref","unstructured":"Millar, C.L., Iloputaife, I., Baldyga, K., Norling, A.M., Boulougoura, A., Vichos, T., Tchkonia, T., Deisinger, A., Pirtskhalava, T., and Kirkland, J.L. (2025). A Pilot Study of Senolytics to Improve Cognition and Mobility in Older Adults at Risk for Alzheimer\u2019s Disease. eBioMedicine, 113.","DOI":"10.1016\/j.ebiom.2025.105612"},{"key":"ref_215","first-page":"1588","article-title":"Immune Remodeling during Aging and the Clinical Significance of Immunonutrition in Healthy Aging","volume":"15","author":"Dou","year":"2023","journal-title":"Aging Dis."},{"key":"ref_216","doi-asserted-by":"crossref","unstructured":"Wu, D., Lewis, E.D., Pae, M., and Meydani, S.N. (2019). Nutritional Modulation of Immune Function: Analysis of Evidence, Mechanisms, and Clinical Relevance. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.03160"},{"key":"ref_217","doi-asserted-by":"crossref","unstructured":"Grabarczyk, M., Justy\u0144ska, W., Czpakowska, J., Smoli\u0144ska, E., Bielenin, A., Glabinski, A., and Szpakowski, P. (2024). Role of Plant Phytochemicals: Resveratrol, Curcumin, Luteolin and Quercetin in Demyelination, Neurodegeneration, and Epilepsy. Antioxidants, 13.","DOI":"10.3390\/antiox13111364"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"22349","DOI":"10.36948\/ijfmr.2024.v06i03.22349","article-title":"Senolytics and Dietary Phytochemicals: Exploring Anti-Aging Strategies and Mechanisms in Aging and Disease","volume":"6","author":"Dias","year":"2024","journal-title":"Int. J. Multidiscip. Res."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1210\/jc.2015-3599","article-title":"Vitamin D Supplementation Modulates T Cell\u2013Mediated Immunity in Humans: Results from a Randomized Control Trial","volume":"101","author":"Konijeti","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_220","doi-asserted-by":"crossref","unstructured":"Carlberg, C., and Velleuer, E. (2024). Vitamin D and Aging: Central Role of Immunocompetence. Nutrients, 16.","DOI":"10.3390\/nu16030398"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.arr.2017.01.001","article-title":"Gut Microbiota: A Player in Aging and a Target for Anti-Aging Intervention","volume":"35","author":"Vaiserman","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.hlife.2023.06.002","article-title":"Fecal Microbiota Transplantation: A New Strategy to Delay Aging","volume":"1","author":"Yan","year":"2023","journal-title":"hLife"},{"key":"ref_223","first-page":"107","article-title":"The Effect of Targeted Probiotics on the Microbiota\u2013Gut\u2013Immune System Axis","volume":"18","author":"Pechkurov","year":"2023","journal-title":"Clin. Pract. Pediatr."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1182\/blood.2022017514","article-title":"Fecal Microbiota Transplantation from Young Mice Rejuvenates Aged Hematopoietic Stem Cells by Suppressing Inflammation","volume":"141","author":"Zeng","year":"2023","journal-title":"Blood"},{"key":"ref_225","doi-asserted-by":"crossref","unstructured":"Parker, A., Romano, S., Ansorge, R., Aboelnour, A., Le Gall, G., Savva, G.M., Pontifex, M.G., Telatin, A., Baker, D., and Jones, E. (2022). Fecal Microbiota Transfer between Young and Aged Mice Reverses Hallmarks of the Aging Gut, Eye, and Brain. Microbiome, 10.","DOI":"10.1186\/s40168-022-01243-w"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"3509","DOI":"10.1080\/10408398.2020.1867054","article-title":"Gut Microbiota and Aging","volume":"62","author":"Ling","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_227","doi-asserted-by":"crossref","unstructured":"Massoud, A., and Rezaei, N. (2014). Aging Immunity and the Impact of Physical Exercise. Immunology of Aging, Springer.","DOI":"10.1007\/978-3-642-39495-9"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.arr.2012.03.003","article-title":"Exercise and the Aging Immune System","volume":"11","author":"Simpson","year":"2012","journal-title":"Ageing Res. Rev."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"60","DOI":"10.31491\/APT.2022.09.088","article-title":"Targeting Metabolism through Exercise and Nutrition to Rejuvenate an Aging Immune System","volume":"4","author":"Pence","year":"2022","journal-title":"Aging Pathobiol. Ther."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1097\/jes.0b013e31802d7008","article-title":"Stress and Exercise: Getting the Balance Right for Aging Immunity","volume":"35","author":"Phillips","year":"2007","journal-title":"Exerc. Sport Sci. Rev."},{"key":"ref_231","doi-asserted-by":"crossref","unstructured":"Garbarino, S., Lanteri, P., Bragazzi, N.L., Magnavita, N., and Scoditti, E. (2021). Role of Sleep Deprivation in Immune-Related Disease Risk and Outcomes. Commun. Biol., 4.","DOI":"10.1038\/s42003-021-02825-4"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S1836-9553(12)70106-6","article-title":"Exercise Training Improves Sleep Quality in Middle-Aged and Older Adults with Sleep Problems: A Systematic Review","volume":"58","author":"Yang","year":"2012","journal-title":"J. Physiother."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.pmu.2019.05.002","article-title":"Lifestyle Medicine\u2014An Evidence Based Approach to Nutrition, Sleep, Physical Activity, and Stress Management on Health and Chronic Illness","volume":"8","author":"Abe","year":"2019","journal-title":"Pers. Med. Universe"},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/agm2.12089","article-title":"Research Progress on Immune Aging and Its Mechanisms Affecting Geriatric Diseases","volume":"2","author":"Yu","year":"2019","journal-title":"Aging Med."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1038\/s41591-024-03483-9","article-title":"Integrating the Environmental and Genetic Architectures of Aging and Mortality","volume":"31","author":"Argentieri","year":"2025","journal-title":"Nat. Med."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s40142-022-00205-w","article-title":"Genetic, Social, and Lifestyle Drivers of Healthy Aging and Longevity","volume":"10","author":"Castruita","year":"2022","journal-title":"Curr. Genet. Med. Rep."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1093\/geroni\/igaa057.2911","article-title":"Navigating the Treacherous Waters of Geriatric Complexity and Heterogeneity With the Help of Team Science","volume":"4","author":"Kuchel","year":"2020","journal-title":"Innov. Aging"},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.smim.2018.10.010","article-title":"Vaccination in the Elderly: The Challenge of Immune Changes with Aging","volume":"40","author":"Ciabattini","year":"2018","journal-title":"Semin. Immunol."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/acr2.11114","article-title":"The Relation of the Chronic Disease Epidemic to the Health Care Crisis","volume":"2","author":"Holman","year":"2020","journal-title":"ACR Open Rheumatol."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s00391-012-0414-3","article-title":"Translationale Forschung in der Geriatrie? Ein Pl\u00e4doyer anhand aktueller biomedizinischer Schl\u00fcsselpublikationen","volume":"46","author":"Bollheimer","year":"2013","journal-title":"Z. Gerontol. Geriatr."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"100185","DOI":"10.1016\/j.aggp.2025.100185","article-title":"Tackling Polypharmacy in Geriatric Patients: Is Increasing Physicians\u2019 Awareness Adequate?","volume":"2","author":"Sutanto","year":"2025","journal-title":"Arch. Gerontol. Geriatr. Plus"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1111\/jgs.16056","article-title":"Translational Geroscience: Challenges and Opportunities for Geriatric Medicine","volume":"67","author":"Gill","year":"2019","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_243","doi-asserted-by":"crossref","unstructured":"Mills, S., Lane, J.A., Smith, G.J., Grimaldi, K.A., Ross, R.P., and Stanton, C. (2019). Precision Nutrition and the Microbiome Part II: Potential Opportunities and Pathways to Commercialisation. Nutrients, 11.","DOI":"10.3390\/nu11071468"},{"key":"ref_244","doi-asserted-by":"crossref","unstructured":"Jain, N. (2020). The Need for Personalized Approaches to Microbiome Modulation. Front. Public Health, 8.","DOI":"10.3389\/fpubh.2020.00144"},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1177\/0706743719890725","article-title":"Decoding Microbiome Research for Clinical Psychiatry","volume":"65","author":"Foster","year":"2020","journal-title":"Can. J. Psychiatry"},{"key":"ref_246","doi-asserted-by":"crossref","unstructured":"Chui, Z.S.W., Chan, L.M.L., Zhang, E.W.H., Liang, S., Choi, E.P.H., Lok, K.Y.W., Tun, H.M., and Kwok, J.Y.Y. (2024). Effects of Microbiome-Based Interventions on Neurodegenerative Diseases: A Systematic Review and Meta-Analysis. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-59250-w"},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"265","DOI":"10.3920\/BM2021.0050","article-title":"Innovations for Microbiome Targeting Interventions\u2014A Patent Landscape Analysis Indicating Overall Patenting Activity Decline and Promising Target Disease Areas","volume":"13","author":"Timmis","year":"2022","journal-title":"Benef. Microbes"},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"22","DOI":"10.14283\/jpad.2021.62","article-title":"Senolytic Therapy to Modulate the Progression of Alzheimer\u2019s Disease (SToMP-AD): A Pilot Clinical Trial","volume":"9","author":"Gonzales","year":"2022","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1038\/s41591-023-02543-w","article-title":"Senolytic Therapy in Mild Alzheimer\u2019s Disease: A Phase 1 Feasibility Trial","volume":"29","author":"Gonzales","year":"2023","journal-title":"Nat. Med."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1111\/jgs.14969","article-title":"The Clinical Potential of Senolytic Drugs","volume":"65","author":"Kirkland","year":"2017","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1093\/emph\/eoae007","article-title":"Senolytics and Cell Senescence: Historical and Evolutionary Perspectives","volume":"12","author":"Finch","year":"2024","journal-title":"Evol. Med. 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