{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T22:07:24Z","timestamp":1784758044134,"version":"3.55.0"},"reference-count":90,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["RHL143545-01A1"],"award-info":[{"award-number":["RHL143545-01A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Several reports have suggested that ageing negatively affects the human body resulting in the alteration of various parameters important for sufficient immune health. Although, the breakdown of innate and adaptive immunity has been hypothesized to increase an individual\u2019s susceptibility to infections including Mycobacterium tuberculosis (M. tb), little research has been done to bridge this gap and understand the pathophysiology underlying how ageing increases the pathogenesis of M. tb infection. Our objective was to study research from a plethora of resources to better understand the pathogenesis of ageing and its link to the human immune system. To achieve this goal, this article explores how ageing decreases the collective T-cell immune response, reduces glutathione (GSH) production, over activates the mammalian target of rapamycin (mTORC1) pathway, inhibits autophagy and mitophagy, and alters various protective genes\/transcription factors. Specifically highlighting how each of these pathways cripple an individual\u2019s immune system and increases their susceptibility from M. tb infection. Furthermore, research summarized in this article gives rise to an additional mechanism of susceptibility to M. tb infection which includes a potential defect in antigen presenting by dendritic cells rather than the T-cells response. Inflammaging has also been shown to play a role in the ageing of the immune system and can also potentially be a driving factor for increased susceptibility to M. tb infection in the elderly. In addition, this article features possible preventative strategies that could decrease infections like M. tb in this population. These strategies would need to be further explored and range from immunomodulators, like Everolimus to antioxidant supplementation through GSH intake. We have also proposed the need to research these therapies in conjunction with the administration of the BCG vaccine, especially in endemic populations, to better understand the risk contracting M. tb infection as well as ways to prevent infection in the first place.<\/jats:p>","DOI":"10.3390\/vaccines10111892","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T02:01:45Z","timestamp":1668045705000},"page":"1892","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Mycobacterium tuberculosis: Implications of Ageing on Infection and Maintaining Protection in the Elderly"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0857-5477","authenticated-orcid":false,"given":"Victor","family":"Bonavida","sequence":"first","affiliation":[{"name":"Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8472-6543","authenticated-orcid":false,"given":"Mitchell","family":"Frame","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4910-3073","authenticated-orcid":false,"given":"Kevin H.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shlok","family":"Rajurkar","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences, University California Berkeley, Berkeley, CA 94720, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2586-1160","authenticated-orcid":false,"given":"Vishwanath","family":"Venketaraman","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/prd.12126","article-title":"The aging population: Demographics and the biology of aging","volume":"72","author":"Kanasi","year":"2016","journal-title":"Periodontology 2000"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1161\/01.CIR.0000086898.96021.B9","article-title":"Aging and Diseases of the Heart","volume":"108","author":"Stern","year":"2003","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1038\/nm0909-996","article-title":"Connecting obesity, aging and diabetes","volume":"15","author":"Ahima","year":"2009","journal-title":"Nat. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Scordo, J.M., Aguill\u00f3n-Dur\u00e1n, G.P., Ayala, D., Quirino-Cerrillo, A.P., Rodr\u00edguez-Reyna, E., Mora-Guzm\u00e1n, F., Caso, J.A., Ledezma-Campos, E., Schlesinger, L.S., and Torrelles, J.B. (2021). A prospective cross-sectional study of tuberculosis in elderly Hispanics reveals that BCG vaccination at birth is protective whereas diabetes is not a risk factor. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0255194"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Suastika, K., Dwipayana, P., Siswadi, M., and Tuty, R.A. (2012). Age is an Important Risk Factor for Type 2 Diabetes Mellitus and Cardiovascular Diseases. Glucose Tolerance, InTech.","DOI":"10.5772\/52397"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"646354","DOI":"10.1155\/2012\/646354","article-title":"Oxidative Stress, Mitochondrial Dysfunction, and Aging","volume":"2012","author":"Cui","year":"2012","journal-title":"J. Signal Transduct."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4524","DOI":"10.1091\/mbc.E14-06-1084","article-title":"The cell biology of aging","volume":"26","author":"DiLoreto","year":"2015","journal-title":"Mol. Biol. Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10347","DOI":"10.1038\/s41598-019-46749-w","article-title":"Discrete Changes in Glucose Metabolism Define Aging","volume":"9","author":"Ravera","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1056\/NEJMra1309483","article-title":"Lactic Acidosis","volume":"371","author":"Kraut","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wu, G., Fang, Y.-Z., Yang, S., Lupton, J.R., and Turner, N.D. (2022, June 29). Recent Advances in Nutritional Sciences Glutathione Metabolism and Its Implications for Health 1. Available Online: https:\/\/academic.oup.com\/jn\/article\/134\/3\/489\/4688681.","DOI":"10.1093\/jn\/134.3.489"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.3389\/fimmu.2018.02569","article-title":"T-Cell Exhaustion in Chronic Infections: Reversing the State of Exhaustion and Reinvigorating Optimal Protective Immune Responses","volume":"9","author":"Saeidi","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nature04444","article-title":"Restoring function in exhausted CD8 T cells during chronic viral infection","volume":"439","author":"Barber","year":"2006","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"211","DOI":"10.4049\/jimmunol.1201108","article-title":"In Vivo Blockade of the PD-1 Receptor Suppresses HIV-1 Viral Loads and Improves CD4+ T Cell Levels in Humanized Mice","volume":"190","author":"Palmer","year":"2012","journal-title":"J. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.coi.2012.12.003","article-title":"T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment","volume":"25","author":"Crespo","year":"2013","journal-title":"Curr. Opin. Immunol."},{"key":"ref_15","first-page":"3","article-title":"Immunology of Aging: The Birth of Inflammaging","volume":"1","author":"Fulop","year":"2016","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1189\/jlb.4A0214-093RR","article-title":"Characterization of lung inflammation and its impact on macrophage function in aging","volume":"96","author":"Canan","year":"2014","journal-title":"J. Leukoc. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.exger.2018.06.029","article-title":"Altered monocyte phenotypes but not impaired peripheral T cell immunity may explain susceptibility of the elderly to develop tuberculosis","volume":"111","author":"Ault","year":"2018","journal-title":"Exp. Gerontol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1126\/science.aax0860","article-title":"T cells with dysfunctional mitochondria induce multimorbidity and premature senescence","volume":"368","author":"Aranda","year":"2020","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0047-6374(96)01812-X","article-title":"The T cell in the ageing individual1This article is based on a presentation to the First International Conference on Aging and Immunology, Bethesda, MD, 16\u201319 June, 1996.1","volume":"93","author":"Pawelec","year":"1997","journal-title":"Mech. Ageing Dev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1093\/intimm\/dxaa006","article-title":"Physiology and pathology of T-cell aging","volume":"32","author":"Minato","year":"2020","journal-title":"Int. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.18632\/aging.203936","article-title":"Increased DNA methylation, cellular senescence and premature epigenetic aging in guinea pigs and humans with tuberculosis","volume":"14","author":"Bobak","year":"2022","journal-title":"Aging"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/BF00918135","article-title":"Transforming Growth Factor Beta (TGF-\u03b2) in Inflammation: A Cause and a Cure","volume":"12","author":"Wahl","year":"1992","journal-title":"J. Clin. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1002\/eji.201243262","article-title":"Mycobacterium tuberculosis-specific CD8+ T cells are functionally and phenotypically different between latent infection and active disease","volume":"43","author":"Rozot","year":"2013","journal-title":"Eur. J. Immunol."},{"key":"ref_24","first-page":"a018499","article-title":"Immunity and Immunopathology in the Tuberculous Granuloma","volume":"5","author":"Ramakrishnan","year":"2014","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"411","DOI":"10.3389\/fimmu.2012.00411","article-title":"The Granuloma in Tuberculosis: Dynamics of a Host\u2013Pathogen Collusion","volume":"3","author":"Ehlers","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/microbiolspec.GPP3-0022-2018","article-title":"Immunology of Mycobacterium tuberculosis Infections","volume":"7","author":"Sia","year":"2019","journal-title":"Microbiol. Spectr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1080\/20477724.2017.1351080","article-title":"New findings of Toll-like receptors involved in Mycobacterium tuberculosis infection","volume":"111","author":"Faridgohar","year":"2017","journal-title":"Pathog. Glob. Health"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1002\/eji.200839115","article-title":"Transcriptional and inflammasome-mediated pathways for the induction of IL-1\u03b2 production by Mycobacterium tuberculosis","volume":"39","author":"Kleinnijenhuis","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1146\/annurev-immunol-093019-010426","article-title":"The Innate Immune Response to Mycobacterium tuberculosis Infection","volume":"39","author":"Stanley","year":"2021","journal-title":"Annu. Rev. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"a018424","DOI":"10.1101\/cshperspect.a018424","article-title":"Innate and Adaptive Cellular Immune Responses to Mycobacterium tuberculosis Infection","volume":"5","author":"Barber","year":"2015","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1172\/JCI136222","article-title":"The knowns and unknowns of latent Mycobacterium tuberculosis infection","volume":"131","author":"Boom","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3329","DOI":"10.1016\/j.bbagen.2012.10.012","article-title":"Glutathione and infection","volume":"1830","author":"Morris","year":"2013","journal-title":"Biochim. Biophys. Acta (BBA)-Gen. Subj."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cell.2018.09.048","article-title":"Biological Functions of Autophagy Genes: A Disease Perspective","volume":"176","author":"Levine","year":"2019","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1080\/22221751.2021.1899771","article-title":"Trained immunity contributes to the prevention of Mycobacterium tuberculosis infection, a novel role of autophagy","volume":"10","author":"Zhou","year":"2021","journal-title":"Emerg. Microbes Infect."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1152\/ajplung.00162.2017","article-title":"Role of apoptosis and autophagy in tuberculosis","volume":"313","author":"Lam","year":"2017","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1080\/21505594.2018.1536598","article-title":"Autophagy: A new strategy for host-directed therapy of tuberculosis","volume":"10","author":"Paik","year":"2019","journal-title":"Virulence"},{"key":"ref_37","first-page":"18","article-title":"A Molecular Approach to Mitophagy and Mitochondrial Dynamics","volume":"41","author":"Yoo","year":"2018","journal-title":"Mol. Cells"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1128\/IAI.00687-20","article-title":"Mitochondria: Powering the Innate Immune Response to Mycobacterium tuberculosis Infection","volume":"89","author":"Patrick","year":"2021","journal-title":"Infect. Immun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.molcel.2016.01.028","article-title":"The Mitochondrial Basis of Aging","volume":"61","author":"Sun","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"102046","DOI":"10.1016\/j.tube.2020.102046","article-title":"NIX-mediated mitophagy regulate metabolic reprogramming in phagocytic cells during mycobacterial infection","volume":"126","author":"Mahla","year":"2020","journal-title":"Tuberculosis"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Mao, Z., and Zhang, W. (2018). Role of mTOR in Glucose and Lipid Metabolism. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19072043"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1172\/JCI73939","article-title":"mTOR: A pharmacologic target for autophagy regulation","volume":"125","author":"Kim","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"473","DOI":"10.4161\/15384101.2014.991572","article-title":"mTOR coordinates protein synthesis, mitochondrial activity and proliferation","volume":"14","author":"Morita","year":"2015","journal-title":"Cell Cycle"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1159\/000484629","article-title":"mTOR as Regulator of Lifespan, Aging, and Cellular Senescence: A Mini-Review","volume":"64","author":"Weichhart","year":"2018","journal-title":"Gerontology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3389\/fmicb.2018.00070","article-title":"Harnessing the mTOR Pathway for Tuberculosis Treatment","volume":"9","author":"Singh","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Cerni, S., Shafer, D., To, K., and Venketaraman, V. (2019). Investigating the Role of Everolimus in mTOR Inhibition and Autophagy Promotion as a Potential Host-Directed Therapeutic Target in Mycobacterium tuberculosis Infection. J. Clin. Med., 8.","DOI":"10.3390\/jcm8020232"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2574","DOI":"10.1002\/eji.201546259","article-title":"Rewiring cellular metabolism via the AKT\/mTOR pathway contributes to host defence against Mycobacterium tuberculosis in human and murine cells","volume":"46","author":"Lachmandas","year":"2016","journal-title":"Eur. J. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1128\/microbiolspec.TBTB2-0023-2016","article-title":"Latent Mycobacterium tuberculosis Infection and Interferon-Gamma Release Assays","volume":"4","author":"Pai","year":"2016","journal-title":"Microbiol. Spectr."},{"key":"ref_49","unstructured":"World Health Organization (2015). Guidelines on the Management of Latent Tuberculosis Infection, Guidelines on the Management of Latent Tuberculosis Infection."},{"key":"ref_50","unstructured":"Pahal, P., and Sharma, S. (2022). PPD Skin Test. Treasure Island (FL), StatPearls Publishing. Available Online: https:\/\/www-ncbi-nlm-nih-gov.proxy.westernu.edu\/books\/NBK556037\/."},{"key":"ref_51","first-page":"271","article-title":"Prospective Comparison of Two Brands of Tuberculin Skin Tests and Quantiferon-TB Gold in-tube Assay Performances for Tuberculosis Infection in Hospitalized Children","volume":"5","author":"Stavri","year":"2010","journal-title":"Maedica"},{"key":"ref_52","first-page":"793","article-title":"Tuberculin PPD RT23: Still going strong Counterpoint","volume":"2","author":"Rosales","year":"1998","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1016\/j.ijid.2019.01.048","article-title":"Tuberculin skin test\u2014Outdated or still useful for Latent TB infection screening?","volume":"80","author":"Gualano","year":"2019","journal-title":"Int. J. Infect. Dis."},{"key":"ref_54","first-page":"49","article-title":"The Role of Interferon-gamma Release Assay in Tuberculosis Control","volume":"63","author":"Mise","year":"2012","journal-title":"Arch. Ind. Hyg. Toxicol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s00011-016-0923-4","article-title":"Characterisation of the clinical and activated T cell response to repeat delayed-type hypersensitivity skin challenges in human subjects, with KLH and PPD, as a potential model to test T cell-targeted therapies","volume":"65","author":"Belson","year":"2016","journal-title":"Inflamm. Res."},{"key":"ref_56","first-page":"1034","article-title":"Tuberculosis and Aging: A Global Health Problem","volume":"33","author":"Rajagopalan","year":"2001","journal-title":"Aging Infect. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"003","DOI":"10.1055\/s-0032-1333467","article-title":"Global Epidemiology of Tuberculosis","volume":"34","author":"Falzon","year":"2013","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"793292","DOI":"10.1155\/2015\/793292","article-title":"Impairments of Antigen-Presenting Cells in Pulmonary Tuberculosis","volume":"2015","author":"Sakhno","year":"2015","journal-title":"J. Immunol. Res."},{"key":"ref_59","unstructured":"McDermott, W., Rogers, D.E., Med, J.H., Bloom, B.R., and Murray, C.J.L. (1982). 15. National MDR-TB Task Force, National Action Plan to Combat Multidrug-Resistant Tuberculosis (Centers for Disease Control), American Society for Microbiology."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.jim.2018.08.005","article-title":"Aging and the immune system: An overview","volume":"463","author":"Akha","year":"2018","journal-title":"J. Immunol. Methods"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.bbabio.2009.02.005","article-title":"Dynamics of mitochondrial structure during apoptosis and the enigma of Opa1","volume":"1787","author":"Yamaguchi","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"12896","DOI":"10.1073\/pnas.95.22.12896","article-title":"Mitochondrial adenine nucleotide translocase is modified oxidatively during aging","volume":"95","author":"Yan","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","unstructured":"Dunn, J., and Grider, M.H. (2022). Physiology, Adenosine Triphosphate. StatPearls, Available Online: https:\/\/pubmed-ncbi-nlm-nih-gov.proxy.westernu.edu\/31985968\/."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1084\/jem.185.8.1481","article-title":"Intracellular Adenosine Triphosphate (ATP) Concentration: A Switch in the Decision Between Apoptosis and Necrosis","volume":"185","author":"Leist","year":"1997","journal-title":"J. Exp. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"101759","DOI":"10.1016\/j.redox.2020.101759","article-title":"Innate-adaptive immunity interplay and redox regulation in immune response","volume":"37","author":"Sun","year":"2020","journal-title":"Redox Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1742-4933-7-4","article-title":"The effect of ageing on human lymphocyte subsets: Comparison of males and females","volume":"7","author":"Yan","year":"2010","journal-title":"Immun. Ageing"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.immuni.2017.03.010","article-title":"Successful and Maladaptive T Cell Aging","volume":"46","author":"Goronzy","year":"2017","journal-title":"Immunity"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1126\/sciimmunol.aag0192","article-title":"Epigenomics of human CD8 T cell differentiation and aging","volume":"2","author":"Moskowitz","year":"2017","journal-title":"Sci. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.immuni.2016.07.008","article-title":"Bioenergetic Insufficiencies Due to Metabolic Alterations Regulated by the Inhibitory Receptor PD-1 Are an Early Driver of CD8 + T Cell Exhaustion","volume":"45","author":"Bengsch","year":"2016","journal-title":"Immunity"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"103409","DOI":"10.1016\/j.ebiom.2021.103409","article-title":"Senescent T cells: A potential biomarker and target for cancer therapy","volume":"68","author":"Zhang","year":"2021","journal-title":"eBioMedicine"},{"key":"ref_71","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_72","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ebiom.2017.03.027","article-title":"Telomeres and Cell Senescence-Size Matters Not","volume":"21","author":"Victorelli","year":"2017","journal-title":"eBioMedicine"},{"key":"ref_73","first-page":"1680","article-title":"T Cell Replicative Senescence in Human Aging","volume":"19","author":"Chou","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Byng-Maddick, R., and Noursadeghi, M. (2016). Does tuberculosis threaten our ageing populations?. BMC Infect. Dis., 16.","DOI":"10.1186\/s12879-016-1451-0"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The Hallmarks of Aging","volume":"153","author":"Blasco","year":"2013","journal-title":"Cell"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"998","DOI":"10.12688\/f1000research.17196.1","article-title":"mTOR as a central regulator of lifespan and aging","volume":"8","author":"Papadopoli","year":"2019","journal-title":"F1000Research"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"621","DOI":"10.3389\/fendo.2018.00621","article-title":"mTORC1 Overactivation as a Key Aging Factor in the Progression to Type 2 Diabetes Mellitus","volume":"9","author":"Benito","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"200","DOI":"10.3389\/fcell.2020.00200","article-title":"Mitophagy: An Emerging Role in Aging and Age-Associated Diseases","volume":"8","author":"Chen","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exger.2015.02.015","article-title":"Effect of age on basal muscle protein synthesis and mTORC1 signaling in a large cohort of young and older men and women","volume":"65","author":"Markofski","year":"2015","journal-title":"Exp. Gerontol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/cbf.937","article-title":"Age-related changes in the glutathione redox system","volume":"20","author":"Sunal","year":"2002","journal-title":"Cell Biochem. Funct."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.brainres.2006.03.063","article-title":"Age-related changes in glutathione and glutathione-related enzymes in rat brain","volume":"1090","author":"Zhu","year":"2006","journal-title":"Brain Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"508","DOI":"10.3389\/fimmu.2015.00508","article-title":"Mechanisms of Control of Mycobacterium tuberculosis by NK Cells: Role of Glutathione","volume":"6","author":"Allen","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1007\/s10989-020-10124-5","article-title":"Proposed Mechanism of Antibacterial Activity of Glutathione by Inhibition of the d-Alanyl-d-alanine Carboxypeptidase Enzyme","volume":"27","author":"Mustikaningtyas","year":"2020","journal-title":"Int. J. Pept. Res. Ther."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3119","DOI":"10.1002\/jcp.29219","article-title":"Nrf2\u2013ARE signaling in cellular protection: Mechanism of action and the regulatory mechanisms","volume":"235","author":"Shaw","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.freeradbiomed.2015.05.036","article-title":"Oxidative stress response and Nrf2 signaling in aging","volume":"88","author":"Zhang","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Matsuyama, M., Nonaka, M., Nakajima, M., Morishima, Y., Ishii, Y., and Hizawa, N. (2021). The Role of NRF2 in Mycobacterial Infection. Antioxidants, 10.","DOI":"10.3390\/antiox10121861"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/s41577-019-0180-1","article-title":"Mechanisms underlying T cell ageing","volume":"19","author":"Goronzy","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1089\/jir.2014.0210","article-title":"Liposomal Glutathione Supplementation Restores TH1 Cytokine Response to Mycobacterium tuberculosis Infection in HIV-Infected Individuals","volume":"35","author":"Ly","year":"2015","journal-title":"J. Interf. Cytokine Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"117594","DOI":"10.1016\/j.lfs.2020.117594","article-title":"Tuberculosis vaccine: A journey from BCG to present","volume":"252","author":"Fatima","year":"2020","journal-title":"Life Sci."},{"key":"ref_90","unstructured":"Satcher, D., Gayle, H.D., Castro, K.G., Thacker, S.B., Goodman, R.A., Hewitt, S.M., Wolcott, L.B., Higgins, M.M., and Jenkins, P.M. (2022, August 27). The Role of BCG Vaccine in the Prevention and Control of Tuberculosis in the United States, Available Online: https:\/\/www.cdc.gov\/mmwr\/pdf\/rr\/rr4504.pdf."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/11\/1892\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:13:23Z","timestamp":1760145203000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/11\/1892"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,9]]},"references-count":90,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["vaccines10111892"],"URL":"https:\/\/doi.org\/10.3390\/vaccines10111892","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,9]]}}}