Evidence-tier classification of anti-infective agents based on the strength, type, and translational relevance of available data across mechanistic, animal, and human studies.
Tier
Evidence types
Examples of drug classes
Strengths
Limitations
Tier 1: In vitro mechanistic evidence
Direct effects of ROS, mitochondrial potential, senescence markers, SASP
The authors thank Lusaka Apex Medical University, School of Health Sciences, and Faculty of Medicine, for their academic and institutional support towards the completion of this manuscript.
Author contributions
CWS: Conceptualization, Writing—original draft, Writing—review & editing. JM: Data curation, Resources, Writing—review & editing. SKD: Methodology, Writing—review & editing, Supervision. AC: Data curation, Visualization, Writing—review & editing. LS: Validation, Resources, Writing—review & editing. KM: Investigation, Formal analysis, Writing—review & editing. All authors read and approved the submitted version.
Conflicts of interest
The authors declare that they have no conflicts of interest.
Ethical approval
Not applicable.
Consent to participate
Not applicable.
Consent to publication
Not applicable.
Availability of data and materials
The dataset used during the study is available from the corresponding author upon request.
Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.
References
Fraser HC, Kuan V, Johnen R, Zwierzyna M, Hingorani AD, Beyer A, et al. Biological mechanisms of aging predict age-related disease co-occurrence in patients.Aging Cell. 2022;21:e13524. [DOI] [PubMed] [PMC]
Abdellatif M, Rainer PP, Sedej S, Kroemer G. Hallmarks of cardiovascular ageing.Nat Rev Cardiol. 2023;20:754–77. [DOI] [PubMed]
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging.Cell. 2013;153:1194–217. [DOI] [PubMed] [PMC]
Vakka A, Warren JS, Drosatos K. Cardiovascular aging: from cellular and molecular changes to therapeutic interventions.J Cardiovasc Aging. 2023;3:23. [DOI] [PubMed] [PMC]
Biga PR, Duan JE, Young TE, Marks JR, Bronikowski A, Decena LP, et al.; IISAGE Consortium. Hallmarks of aging: A user’s guide for comparative biologists.Ageing Res Rev. 2025;104:102616. [DOI] [PubMed]
Kritsilis M, V Rizou S, Koutsoudaki PN, Evangelou K, Gorgoulis VG, Papadopoulos D. Ageing, Cellular Senescence and Neurodegenerative Disease.Int J Mol Sci. 2018;19:2937. [DOI] [PubMed] [PMC]
Huang W, Hickson LJ, Eirin A, Kirkland JL, Lerman LO. Cellular senescence: the good, the bad and the unknown.Nat Rev Nephrol. 2022;18:611–27. [DOI] [PubMed] [PMC]
Childs BG, Baker DJ, Wijshake T, Conover CA, Campisi J, van Deursen JM. Senescent intimal foam cells are deleterious at all stages of atherosclerosis.Science. 2016;354:472–7. [DOI] [PubMed] [PMC]
Zhou D, Borsa M, Simon AK. Hallmarks and detection techniques of cellular senescence and cellular ageing in immune cells.Aging Cell. 2021;20:e13316. [DOI] [PubMed] [PMC]
McHugh D, Gil J. Senescence and aging: Causes, consequences, and therapeutic avenues.J Cell Biol. 2018;217:65–77. [DOI] [PubMed] [PMC]
Illoh KO, Illoh OC, Feseha HB, Hallenbeck JM. Antibiotics for vascular diseases: a meta-analysis of randomized controlled trials.Atherosclerosis. 2005;179:403–12. [DOI] [PubMed]
Kirkland JL, Tchkonia T. Senolytic drugs: from discovery to translation.J Intern Med. 2020;288:518–36. [DOI] [PubMed] [PMC]
Luís C, Maduro AT, Pereira P, Mendes JJ, Soares R, Ramalho R. Nutritional senolytics and senomorphics: Implications to immune cells metabolism and aging - from theory to practice.Front Nutr. 2022;9:958563. [DOI] [PubMed] [PMC]
Hwang HJ, Kim N, Herman AB, Gorospe M, Lee JS. Factors and Pathways Modulating Endothelial Cell Senescence in Vascular Aging.Int J Mol Sci. 2022;23:10135. [DOI] [PubMed] [PMC]
Csiszar A, Wang M, Lakatta EG, Ungvari Z. Inflammation and endothelial dysfunction during aging: role of NF-kappaB.J Appl Physiol (1985). 2008;105:1333–41. [DOI] [PubMed] [PMC]
Picos A, Seoane N, Campos-Toimil M, Viña D. Vascular senescence and aging: mechanisms, clinical implications, and therapeutic prospects.Biogerontology. 2025;26:118. [DOI] [PubMed] [PMC]
Takahashi A, Ohtani N, Hara E. Irreversibility of cellular senescence: dual roles of p16INK4a/Rb-pathway in cell cycle control.Cell Div. 2007;2:10. [DOI] [PubMed] [PMC]
Liang R, Qi X, Cai Q, Niu L, Huang X, Zhang D, et al. The role of NLRP3 inflammasome in aging and age-related diseases.Immun Ageing. 2024;21:14. [DOI] [PubMed] [PMC]
Iakovou E, Kourti M. A Comprehensive Overview of the Complex Role of Oxidative Stress in Aging, The Contributing Environmental Stressors and Emerging Antioxidant Therapeutic Interventions.Front Aging Neurosci. 2022;14:827900. [DOI] [PubMed] [PMC]
Park SJ, Kim M, Jeong S, Choi S, Park YJ, Kim HJ, et al. Antibiotic Exposure and Cardiovascular Disease Risk: A Nationwide Cohort Study.J Am Heart Assoc. 2025;14:e035888. [DOI] [PubMed] [PMC]
Yu A, Jansen MAC, Dalmeijer GW, Bruijning-Verhagen P, van der Ent CK, Grobbee DE, et al. Childhood infection burden, recent antibiotic exposure and vascular phenotypes in preschool children.PLoS One. 2023;18:e0290633. [DOI] [PubMed] [PMC]
Snell TW, Johnston RK, Matthews AB, Zhou H, Gao M, Skolnick J. Repurposed FDA-approved drugs targeting genes influencing aging can extend lifespan and healthspan in rotifers.Biogerontology. 2018;19:145–57. [DOI] [PubMed] [PMC]
Wang M, Zhang J, Qiu J, Ma X, Xu C, Wu Q, et al. Doxycycline decelerates aging in progeria mice.Aging Cell. 2024;23:e14188. [DOI] [PubMed] [PMC]
Miller M, Singer M. Do antibiotics cause mitochondrial and immune cell dysfunction? A literature review.J Antimicrob Chemother. 2022;77:1218–27. [DOI] [PubMed]
Sailer J, Schmitt S, Zischka H, Gnaiger E. Direct Effects of Clinically Relevant Antibiotics on Mitochondrial Respiration.Int J Mol Sci. 2025;26:5379. [DOI] [PubMed] [PMC]
Lathakumari RH, Vajravelu LK, Satheesan A, Ravi S, Thulukanam J. Antibiotics and the gut microbiome: Understanding the impact on human health.Med Microecol. 2024;20:100106. [DOI]
Zhou X, Lu J, Wei K, Wei J, Tian P, Yue M, et al. Neuroprotective Effect of Ceftriaxone on MPTP-Induced Parkinson’s Disease Mouse Model by Regulating Inflammation and Intestinal Microbiota.Oxid Med Cell Longev. 2021;2021:9424582. [DOI] [PubMed] [PMC]
Clayton ZS, Hutton DA, Mahoney SA, Seals DR. Anthracycline chemotherapy-mediated vascular dysfunction as a model of accelerated vascular aging.Aging Cancer. 2021;2:45–69. [DOI] [PubMed] [PMC]
Suárez-Rivero JM, López-Pérez J, Muela-Zarzuela I, Pastor-Maldonado C, Cilleros-Holgado P, Gómez-Fernández D, et al. Neurodegeneration, Mitochondria, and Antibiotics.Metabolites. 2023;13:416. [DOI] [PubMed] [PMC]
Zimmermann P, Ziesenitz VC, Curtis N, Ritz N. The Immunomodulatory Effects of Macrolides-A Systematic Review of the Underlying Mechanisms.Front Immunol. 2018;9:302. [DOI] [PubMed] [PMC]
Bonuccelli G, Brooks DR, Shepherd S, Sotgia F, Lisanti MP. Antibiotics that target mitochondria extend lifespan in C. elegans.Aging (Albany NY). 2023;15:11764–81. [DOI] [PubMed] [PMC]
Hu Z, Zhou J, Han L, Li X, Li C, Wu T, et al. Acyclovir alleviates insulin resistance via activating PKM1 in diabetic mice.Life Sci. 2022;304:120725. [DOI] [PubMed]
Bick AG, Popadin K, Thorball CW, Uddin MM, Zanni MV, Yu B, et al.; Swiss HIV Cohort Study. Increased prevalence of clonal hematopoiesis of indeterminate potential amongst people living with HIV.Sci Rep. 2022;12:577. [DOI] [PubMed] [PMC]
Rocco JM, Zhou Y, Liu NS, Laidlaw E, Galindo F, Anderson MV, et al. Clonal hematopoiesis in people with advanced HIV and associated inflammatory syndromes.JCI Insight. 2024;9:e174783. [DOI] [PubMed] [PMC]
Aminov RI. A brief history of the antibiotic era: lessons learned and challenges for the future.Front Microbiol. 2010;1:134. [DOI] [PubMed] [PMC]
Ventola CL. The antibiotic resistance crisis: part 1: causes and threats.P T. 2015;40:277–83. [PubMed] [PMC]
Gouzos M, Ramezanpour M, Bassiouni A, Psaltis AJ, Wormald PJ, Vreugde S. Antibiotics Affect ROS Production and Fibroblast Migration in an In-vitro Model of Sinonasal Wound Healing.Front Cell Infect Microbiol. 2020;10:110. [DOI] [PubMed] [PMC]
Bayer F, Ascher S, Pontarollo G, Reinhardt C. Antibiotic Treatment Protocols and Germ-Free Mouse Models in Vascular Research.Front Immunol. 2019;10:2174. [DOI] [PubMed] [PMC]
Zeng W, Liang Y, Huang S, Zhang J, Mai C, He B, et al. Ciprofloxacin Accelerates Angiotensin-II-Induced Vascular Smooth Muscle Cells Senescence Through Modulating AMPK/ROS pathway in Aortic Aneurysm and Dissection.Cardiovasc Toxicol. 2024;24:889–903. [DOI] [PubMed] [PMC]
Neves MF, Cunha AR, Cunha MR, Gismondi RA, Oigman W. The Role of Renin-Angiotensin-Aldosterone System and Its New Components in Arterial Stiffness and Vascular Aging.High Blood Press Cardiovasc Prev. 2018;25:137–45. [DOI] [PubMed]
Conti S, Cassis P, Benigni A. Aging and the renin-angiotensin system.Hypertension. 2012;60:878–83. [DOI] [PubMed]
Casagrande Raffi G, Chen J, Feng X, Chen Z, Lieftink C, Deng S, et al. An antibiotic that mediates immune destruction of senescent cancer cells.Proc Natl Acad Sci U S A. 2024;121:e2417724121. [DOI] [PubMed] [PMC]
Liu S, He Y, Zhang Y, Zhang Z, Huang K, Deng L, et al. Targeting gut microbiota in aging-related cardiovascular dysfunction: focus on the mechanisms.Gut Microbes. 2023;15:2290331. [DOI] [PubMed] [PMC]
Li J, Wang Y, Shrestha S, Gewirtz AT, Ding Y, Zou J. Targeting Gut Microbiota to Combat Vascular Aging and Cardiovascular Disease: Mechanisms and Therapeutic Potential.Nutrients. 2025;17:2887. [DOI] [PubMed] [PMC]
Li S, Liu J, Zhang X, Gu Q, Wu Y, Tao X, et al. The Potential Impact of Antibiotic Exposure on the Microbiome and Human Health.Microorganisms. 2025;13:602. [DOI] [PubMed] [PMC]
Brunt VE, Gioscia-Ryan RA, Casso AG, VanDongen NS, Ziemba BP, Sapinsley ZJ, et al. Trimethylamine-N-Oxide Promotes Age-Related Vascular Oxidative Stress and Endothelial Dysfunction in Mice and Healthy Humans.Hypertension. 2020;76:101–12. [DOI] [PubMed] [PMC]
Wang C, Ma Q, Yu X. Bile Acid Network and Vascular Calcification-Associated Diseases: Unraveling the Intricate Connections and Therapeutic Potential.Clin Interv Aging. 2023;18:1749–67. [DOI] [PubMed] [PMC]
Qu Q, Chen Y, Wang Y, Long S, Wang W, Yang HY, et al. Lithocholic acid phenocopies anti-ageing effects of calorie restriction.Nature. 2025;643:192–200. [DOI] [PubMed] [PMC]
Zhao M, Chu J, Feng S, Guo C, Xue B, He K, et al. Immunological mechanisms of inflammatory diseases caused by gut microbiota dysbiosis: A review.Biomed Pharmacother. 2023;164:114985. [DOI] [PubMed]
Ticinesi A, Nouvenne A, Cerundolo N, Catania P, Prati B, Tana C, et al. Gut Microbiota, Muscle Mass and Function in Aging: A Focus on Physical Frailty and Sarcopenia.Nutrients. 2019;11:1633. [DOI] [PubMed] [PMC]
Fransen F, van Beek AA, Borghuis T, Aidy SE, Hugenholtz F, van der Gaast-de Jongh C, et al. Aged Gut Microbiota Contributes to Systemical Inflammaging after Transfer to Germ-Free Mice.Front Immunol. 2017;8:1385. [DOI] [PubMed] [PMC]
Kalghatgi S, Spina CS, Costello JC, Liesa M, Morones-Ramirez JR, Slomovic S, et al. Bactericidal antibiotics induce mitochondrial dysfunction and oxidative damage in Mammalian cells.Sci Transl Med. 2013;5:192ra85. [DOI] [PubMed] [PMC]
Donato AJ, Morgan RG, Walker AE, Lesniewski LA. Cellular and molecular biology of aging endothelial cells.J Mol Cell Cardiol. 2015;89:122–35. [DOI] [PubMed] [PMC]
Templeman NM, Murphy CT. Regulation of reproduction and longevity by nutrient-sensing pathways.J Cell Biol. 2018;217:93–106. [DOI] [PubMed] [PMC]
Pignatti C, D’Adamo S, Stefanelli C, Flamigni F, Cetrullo S. Nutrients and Pathways that Regulate Health Span and Life Span.Geriatrics (Basel). 2020;5:95. [DOI] [PubMed] [PMC]
Thevaranjan N, Puchta A, Schulz C, Naidoo A, Szamosi JC, Verschoor CP, et al. Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic Inflammation, and Macrophage Dysfunction.Cell Host Microbe. 2017;21:455–66.e4. [DOI] [PubMed] [PMC]
Jang DH, Shin JW, Shim E, Ohtani N, Jeon OH. The connection between aging, cellular senescence and gut microbiome alterations: A comprehensive review.Aging Cell. 2024;23:e14315. [DOI] [PubMed] [PMC]
Cusumano G, Flores GA, Venanzoni R, Angelini P. The Impact of Antibiotic Therapy on Intestinal Microbiota: Dysbiosis, Antibiotic Resistance, and Restoration Strategies.Antibiotics (Basel). 2025;14:371. [DOI] [PubMed] [PMC]
Theodorakis N, Feretzakis G, Hitas C, Kreouzi M, Kalantzi S, Spyridaki A, et al. Immunosenescence: How Aging Increases Susceptibility to Bacterial Infections and Virulence Factors.Microorganisms. 2024;12:2052. [DOI] [PubMed] [PMC]
Correia-Melo C, Marques FD, Anderson R, Hewitt G, Hewitt R, Cole J, et al. Mitochondria are required for pro-ageing features of the senescent phenotype.EMBO J. 2016;35:724–42. [DOI] [PubMed] [PMC]
Alvandi R, Salimiyan S, Moradzad M, Mohammadi M, Fakhari S, Rahmani MR. Vitamin C, doxycycline, and azithromycin (VDA) targeted changes in cellular senescence-related genes in human adipose-derived mesenchymal stem cells.Iran J Basic Med Sci. 2024;27:1380–8. [DOI] [PubMed] [PMC]
Li X, Khan D, Rana M, Hänggi D, Muhammad S. Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases.Antioxidants (Basel). 2022;11:2413. [DOI] [PubMed] [PMC]
Rodrigues KE, Azevedo A, Gonçalves PR, Pontes MHB, Alves GM, Oliveira RR, et al. Doxycycline Decreases Atherosclerotic Lesions in the Aorta of ApoE-⁄- and Ovariectomized Mice with Correlation to Reduced MMP-2 Activity.Int J Mol Sci. 2022;23:2532. [DOI] [PubMed] [PMC]
Robles-Vera I, de la Visitación N, Toral M, Sánchez M, Romero M, Gómez-Guzmán M, et al. Changes in Gut Microbiota Induced by Doxycycline Influence in Vascular Function and Development of Hypertension in DOCA-Salt Rats.Nutrients. 2021;13:2971. [DOI] [PubMed] [PMC]
Fischer BM, Wong JK, Degan S, Kummarapurugu AB, Zheng S, Haridass P, et al. Increased expression of senescence markers in cystic fibrosis airways.Am J Physiol Lung Cell Mol Physiol. 2013;304:L394–400. [DOI] [PubMed] [PMC]
Sargiacomo C, Sotgia F, Lisanti MP. COVID-19 and chronological aging: senolytics and other anti-aging drugs for the treatment or prevention of corona virus infection?Aging (Albany NY). 2020;12:6511–7. [DOI] [PubMed] [PMC]
Sonehara R, Nakamura T, Takeda T, Kaseki S, Seki T, Tanaka H, et al. A novel senotherapeutic strategy with azithromycin for preventing endometriosis progression.Reprod Biol Endocrinol. 2025;23:47. [DOI] [PubMed] [PMC]
Ramirez J, Guarner F, Bustos Fernandez L, Maruy A, Sdepanian VL, Cohen H. Antibiotics as Major Disruptors of Gut Microbiota.Front Cell Infect Microbiol. 2020;10:572912. [DOI] [PubMed] [PMC]
Janeiro MH, Ramírez MJ, Milagro FI, Martínez JA, Solas M. Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target.Nutrients. 2018;10:1398. [DOI] [PubMed] [PMC]
Iliev ID, Leonardi I. Fungal dysbiosis: immunity and interactions at mucosal barriers.Nat Rev Immunol. 2017;17:635–46. [DOI] [PubMed] [PMC]
Heng X, Jiang Y, Chu W. Influence of Fluconazole Administration on Gut Microbiome, Intestinal Barrier, and Immune Response in Mice.Antimicrob Agents Chemother. 2021;65:e02552–20. [DOI] [PubMed] [PMC]
Gaspar BS, Roşu OA, Enache RM, Manciulea Profir M, Pavelescu LA, Creţoiu SM. Gut Mycobiome: Latest Findings and Current Knowledge Regarding Its Significance in Human Health and Disease.J Fungi (Basel). 2025;11:333. [DOI] [PubMed] [PMC]
Ray S, Narayanan A, Giske CG, Neogi U, Sönnerborg A, Nowak P. Altered Gut Microbiome under Antiretroviral Therapy: Impact of Efavirenz and Zidovudine.ACS Infect Dis. 2021;7:1104–15. [DOI] [PubMed] [PMC]
Spatz M, Da Costa G, Ventin-Holmberg R, Planchais J, Michaudel C, Wang Y, et al. Antibiotic treatment using amoxicillin-clavulanic acid impairs gut mycobiota development through modification of the bacterial ecosystem.Microbiome. 2023;11:73. [DOI] [PubMed] [PMC]
Xu KY, Xia GH, Lu JQ, Chen MX, Zhen X, Wang S, et al. Impaired renal function and dysbiosis of gut microbiota contribute to increased trimethylamine-N-oxide in chronic kidney disease patients.Sci Rep. 2017;7:1445. [DOI] [PubMed] [PMC]
Krishnamurthy HK, Pereira M, Bosco J, George J, Jayaraman V, Krishna K, et al. Gut commensals and their metabolites in health and disease.Front Microbiol. 2023;14:1244293. [DOI] [PubMed] [PMC]
Leonardi I, Li X, Semon A, Li D, Doron I, Putzel G, et al. CX3CR1+ mononuclear phagocytes control immunity to intestinal fungi.Science. 2018;359:232–6. [DOI] [PubMed] [PMC]
Sam QH, Chang MW, Chai LY. The Fungal Mycobiome and Its Interaction with Gut Bacteria in the Host.Int J Mol Sci. 2017;18:330. [DOI] [PubMed] [PMC]
Bradley E, Haran J. The human gut microbiome and aging.Gut Microbes. 2024;16:2359677. [DOI] [PubMed] [PMC]
Vilchez D, Saez I, Dillin A. The role of protein clearance mechanisms in organismal ageing and age-related diseases.Nat Commun. 2014;5:5659. [DOI] [PubMed]
Ungvari Z, Tarantini S, Sorond F, Merkely B, Csiszar A. Mechanisms of Vascular Aging, A Geroscience Perspective: JACC Focus Seminar.J Am Coll Cardiol. 2020;75:931–41. [DOI] [PubMed] [PMC]
Wan Q, Song D, Li H, He ML. Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development.Signal Transduct Target Ther. 2020;5:125. [DOI] [PubMed] [PMC]
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe.Cell. 2023;186:243–78. [DOI] [PubMed]
Cavinato M, Madreiter-Sokolowski CT, Büttner S, Schosserer M, Zwerschke W, Wedel S, et al. Targeting cellular senescence based on interorganelle communication, multilevel proteostasis, and metabolic control.FEBS J. 2021;288:3834–54. [DOI] [PubMed] [PMC]
Zhang Z, Yao Z, Zhao S, Shao J, Chen A, Zhang F, et al. Interaction between autophagy and senescence is required for dihydroartemisinin to alleviate liver fibrosis.Cell Death Dis. 2017;8:e2886. [DOI] [PubMed] [PMC]
Wohlgemuth I, Garofalo R, Samatova E, Günenç AN, Lenz C, Urlaub H, et al. Translation error clusters induced by aminoglycoside antibiotics.Nat Commun. 2021;12:1830. [DOI] [PubMed] [PMC]
Drummond DA. How infidelity creates a sticky situation.Mol Cell. 2012;48:663–4. [DOI] [PubMed] [PMC]
Ling J, Cho C, Guo LT, Aerni HR, Rinehart J, Söll D. Protein aggregation caused by aminoglycoside action is prevented by a hydrogen peroxide scavenger.Mol Cell. 2012;48:713–22. [DOI] [PubMed] [PMC]
Sanchez-Garrido J, Shenoy AR. Regulation and repurposing of nutrient sensing and autophagy in innate immunity.Autophagy. 2021;17:1571–91. [DOI] [PubMed] [PMC]
Renna M, Schaffner C, Brown K, Shang S, Tamayo MH, Hegyi K, et al. Azithromycin blocks autophagy and may predispose cystic fibrosis patients to mycobacterial infection.J Clin Invest. 2011;121:3554–63. [DOI] [PubMed] [PMC]
Doeppner TR, Coman C, Burdusel D, Ancuta DL, Brockmeier U, Pirici DN, et al. Long-term treatment with chloroquine increases lifespan in middle-aged male mice possibly via autophagy modulation, proteasome inhibition and glycogen metabolism.Aging (Albany NY). 2022;14:4195–210. [DOI] [PubMed] [PMC]
Liu X, Xiong W, Ye M, Lu T, Yuan K, Chang S, et al. Non-coding RNAs expression in SARS-CoV-2 infection: pathogenesis, clinical significance, and therapeutic targets.Signal Transduct Target Ther. 2023;8:441. [DOI] [PubMed] [PMC]
Cheng Y, Liang Y, Tan X, Liu L. Host long noncoding RNAs in bacterial infections.Front Immunol. 2024;15:1419782. [DOI] [PubMed] [PMC]
Crimi E, Benincasa G, Cirri S, Mutesi R, Faenza M, Napoli C. Clinical epigenetics and multidrug-resistant bacterial infections: host remodelling in critical illness.Epigenetics. 2020;15:1021–34. [DOI] [PubMed] [PMC]
Wang J, Zhang L, Wang T, Li C, Jiao L, Zhao Z, et al. miRNA-576 Alleviates the Malignant Progression of Atherosclerosis through Downregulating KLF5.Dis Markers. 2021;2021:5450685. [DOI] [PubMed] [PMC]
Manni E, Jeffery N, Chambers D, Slade L, Etheridge T, Harries LW. An evaluation of the role of miR-361-5p in senescence and systemic ageing.Exp Gerontol. 2023;174:112127. [DOI] [PubMed]
Chen DY, Chen YM, Lin CF, Lo CM, Liu HJ, Liao TL. MicroRNA-889 Inhibits Autophagy To Maintain Mycobacterial Survival in Patients with Latent Tuberculosis Infection by Targeting TWEAK.mBio. 2020;11:e03045–19. [DOI] [PubMed] [PMC]
Wang J, Li Y, Wang H, Meng Q, Li P, Wang Y, et al. Harnessing miRNA therapeutics: a novel approach to combat heart and brain infarctions in atherosclerosis.Cell Death Discov. 2025;11:482. [DOI] [PubMed] [PMC]
Sarker P, Mily A, Mamun AA, Jalal S, Bergman P, Raqib R, et al. Ciprofloxacin Affects Host Cells by Suppressing Expression of the Endogenous Antimicrobial Peptides Cathelicidins and Beta-Defensin-3 in Colon Epithelia.Antibiotics (Basel). 2014;3:353–74. [DOI] [PubMed] [PMC]
Ljubić S, Matulić M, Đermić D, Feliciello MC, Procino A, Ugarković Đ, et al. Antibiotics induce overexpression of alpha satellite DNA accompanied with epigenetic changes at alpha satellite arrays as well as genome-wide.Epigenetics Chromatin. 2025;18:62. [DOI] [PubMed] [PMC]
Hildebrandt-Eriksen ES, Aarup V, Persson R, Hansen HF, Munk ME, Ørum H. A locked nucleic acid oligonucleotide targeting microRNA 122 is well-tolerated in cynomolgus monkeys.Nucleic Acid Ther. 2012;22:152–61. [DOI] [PubMed]
Fu Y, Wang B, Alu A, Hong W, Lei H, He X, et al. Immunosenescence: signaling pathways, diseases and therapeutic targets.Signal Transduct Target Ther. 2025;10:250. [DOI] [PubMed] [PMC]
Wu Y, Jiang L, Zhang L, Liu X, Yan L, Luan T, et al. Antifungal Effect of Long Noncoding RNA 9708-1 in the Vulvovaginal Candidiasis Murine Model.Mycopathologia. 2021;186:177–88. [DOI] [PubMed] [PMC]
Hum C, Loiselle J, Ahmed N, Shaw TA, Toudic C, Pezacki JP. MicroRNA Mimics or Inhibitors as Antiviral Therapeutic Approaches Against COVID-19.Drugs. 2021;81:517–31. [DOI] [PubMed] [PMC]
de Kanter JK, Peci F, Bertrums E, Rosendahl Huber A, van Leeuwen A, van Roosmalen MJ, et al. Antiviral treatment causes a unique mutational signature in cancers of transplantation recipients.Cell Stem Cell. 2021;28:1726–39.e6. [DOI] [PubMed] [PMC]
Xu X, Pang Y, Fan X. Mitochondria in oxidative stress, inflammation and aging: from mechanisms to therapeutic advances.Signal Transduct Target Ther. 2025;10:190. [DOI] [PubMed] [PMC]
Krautkramer KA, Kreznar JH, Romano KA, Vivas EI, Barrett-Wilt GA, Rabaglia ME, et al. Diet-Microbiota Interactions Mediate Global Epigenetic Programming in Multiple Host Tissues.Mol Cell. 2016;64:982–92. [DOI] [PubMed] [PMC]
Saiman Y, Shen TD, Lund PJ, Gershuni VM, Jang C, Patel S, et al. Global Microbiota-Dependent Histone Acetylation Patterns Are Irreversible and Independent of Short Chain Fatty Acids.Hepatology. 2021;74:3427–40. [DOI] [PubMed] [PMC]
Kuehnemann C, Hughes JB, Desprez PY, Melov S, Wiley CD, Campisi J. Antiretroviral protease inhibitors induce features of cellular senescence that are reversible upon drug removal.Aging Cell. 2023;22:e13750. [DOI] [PubMed] [PMC]
Delpino MV, Quarleri J. Mitochondrial Dysfunction in Aging, HIV, and Long COVID: Mechanisms and Therapeutic Opportunities.Pathogens. 2025;14:1045. [DOI] [PubMed] [PMC]
Lefèvre C, Auclair M, Boccara F, Bastard JP, Capeau J, Vigouroux C, et al. Premature senescence of vascular cells is induced by HIV protease inhibitors: implication of prelamin A and reversion by statin.Arterioscler Thromb Vasc Biol. 2010;30:2611–20. [DOI] [PubMed]
Kohli J, Veenstra I, Demaria M. The struggle of a good friend getting old: cellular senescence in viral responses and therapy.EMBO Rep. 2021;22:e52243. [DOI] [PubMed] [PMC]
Conklin BS, Fu W, Lin PH, Lumsden AB, Yao Q, Chen C. HIV protease inhibitor ritonavir decreases endothelium-dependent vasorelaxation and increases superoxide in porcine arteries.Cardiovasc Res. 2004;63:168–75. [DOI] [PubMed]
Grosicki M, Wojnar-Lason K, Mosiolek S, Mateuszuk L, Stojak M, Chlopicki S. Distinct profile of antiviral drugs effects in aortic and pulmonary endothelial cells revealed by high-content microscopy and cell painting assays.Toxicol Appl Pharmacol. 2024;490:117030. [DOI] [PubMed]
Kanmogne GD. HIV Infection, Antiretroviral Drugs, and the Vascular Endothelium.Cells. 2024;13:672. [DOI] [PubMed] [PMC]
Wallace J, Gonzalez H, Rajan R, Narasipura SD, Virdi AK, Olali AZ, et al. Anti-HIV Drugs Cause Mitochondrial Dysfunction in Monocyte-Derived Macrophages.Antimicrob Agents Chemother. 2022;66:e0194121. [DOI] [PubMed] [PMC]
Auclair M, Guénantin AC, Fellahi S, Garcia M, Capeau J. HIV antiretroviral drugs, dolutegravir, maraviroc and ritonavir-boosted atazanavir use different pathways to affect inflammation, senescence and insulin sensitivity in human coronary endothelial cells.PLoS One. 2020;15:e0226924. [DOI] [PubMed] [PMC]
Zhan J, Qin S, Lu L, Hu X, Zhou J, Sun Y, et al. miR-34a is a common link in both HIV- and antiretroviral therapy-induced vascular aging.Aging (Albany NY). 2016;8:3298–310. [DOI] [PubMed] [PMC]
Zhao T, Li J, Chen AF. MicroRNA-34a induces endothelial progenitor cell senescence and impedes its angiogenesis via suppressing silent information regulator 1.Am J Physiol Endocrinol Metab. 2010;299:E110–6. [DOI] [PubMed] [PMC]
Hu G, Liao K, Yang L, Pendyala G, Kook Y, Fox HS, et al. Tat-Mediated Induction of miRs-34a & -138 Promotes Astrocytic Activation via Downregulation of SIRT1: Implications for Aging in HAND.J Neuroimmune Pharmacol. 2017;12:420–32. [DOI] [PubMed] [PMC]
Hua CC, Liu XM, Liang LR, Wang LF, Zhong JC. Targeting the microRNA-34a as a Novel Therapeutic Strategy for Cardiovascular Diseases.Front Cardiovasc Med. 2022;8:784044. [DOI] [PubMed] [PMC]
Rashid F, Zaongo SD, Song F, Chen Y. The diverse roles of miRNAs in HIV pathogenesis: Current understanding and future perspectives.Front Immunol. 2023;13:1091543. [DOI] [PubMed] [PMC]
Mondal D, Pradhan L, Ali M, Agrawal KC. HAART drugs induce oxidative stress in human endothelial cells and increase endothelial recruitment of mononuclear cells: exacerbation by inflammatory cytokines and amelioration by antioxidants.Cardiovasc Toxicol. 2004;4:287–302. [DOI] [PubMed]
Chen YF, Dugas TR. Endothelial mitochondrial senescence accelerates cardiovascular disease in antiretroviral-receiving HIV patients.Toxicol Lett. 2019;317:13–23. [DOI] [PubMed]
Head SA, Shi W, Zhao L, Gorshkov K, Pasunooti K, Chen Y, et al. Antifungal drug itraconazole targets VDAC1 to modulate the AMPK/mTOR signaling axis in endothelial cells.Proc Natl Acad Sci U S A. 2015;112:E7276–85. [DOI] [PubMed] [PMC]
Nacev BA, Grassi P, Dell A, Haslam SM, Liu JO. The antifungal drug itraconazole inhibits vascular endothelial growth factor receptor 2 (VEGFR2) glycosylation, trafficking, and signaling in endothelial cells.J Biol Chem. 2011;286:44045–56. [DOI] [PubMed] [PMC]
Chong CR, Xu J, Lu J, Bhat S, Sullivan DJ Jr, Liu JO. Inhibition of angiogenesis by the antifungal drug itraconazole.ACS Chem Biol. 2007;2:263–70. [DOI] [PubMed]
Li F, Song S, Huang M, Xu Y, Zhao B, Liu Z, et al. Miconazole alleviates colitis by suppressing colonic senescence, NF-κB Signaling and gut microbiota modulation.Toxicol Appl Pharmacol. 2025;503:117488. [DOI] [PubMed]
Pelzmann B, Di Giuro CM, Zorn-Pauly K, Rossmann C, Hallström S, Groschner K, et al. Functional impairment of endothelial cells by the antimycotic amphotericin B.Biochem Biophys Res Commun. 2016;472:40–5. [DOI] [PubMed]
Braun JA, Herrmann AL, Blase JI, Frensemeier K, Bulkescher J, Scheffner M, et al. Effects of the antifungal agent ciclopirox in HPV-positive cancer cells: Repression of viral E6/E7 oncogene expression and induction of senescence and apoptosis.Int J Cancer. 2020;146:461–74. [DOI] [PubMed]
Cha HJ, Byrom M, Mead PE, Ellington AD, Wallingford JB, Marcotte EM. Evolutionarily repurposed networks reveal the well-known antifungal drug thiabendazole to be a novel vascular disrupting agent.PLoS Biol. 2012;10:e1001379. [DOI] [PubMed] [PMC]
Yalcin G, Lee CK. The Discovery of Druggable Anti-aging Agents.Ann Geriatr Med Res. 2020;24:232–42. [DOI] [PubMed] [PMC]
Choi PG, Kim HS, Park SH, Seo HD, Hahm JH, Huh YH, et al. Niclosamide extends health span and reduces frailty by ameliorating mTORC1 hyperactivation in aging models.J Adv Res. 2025;[Epub ahead of print]. [DOI] [PubMed]
Ozsvari B, Nuttall JR, Sotgia F, Lisanti MP. Azithromycin and Roxithromycin define a new family of “senolytic” drugs that target senescent human fibroblasts.Aging (Albany NY). 2018;10:3294–307. [DOI] [PubMed] [PMC]
Sharma RK, Yang T, Oliveira AC, Lobaton GO, Aquino V, Kim S, et al. Microglial Cells Impact Gut Microbiota and Gut Pathology in Angiotensin II-Induced Hypertension.Circ Res. 2019;124:727–36. [DOI] [PubMed] [PMC]
Yang T, Santisteban MM, Rodriguez V, Li E, Ahmari N, Carvajal JM, et al. Gut dysbiosis is linked to hypertension.Hypertension. 2015;65:1331–40. [DOI] [PubMed] [PMC]
Brunt VE, Gioscia-Ryan RA, Richey JJ, Zigler MC, Cuevas LM, Gonzalez A, et al. Suppression of the gut microbiome ameliorates age-related arterial dysfunction and oxidative stress in mice.J Physiol. 2019;597:2361–78. [DOI] [PubMed] [PMC]
Abraham P, Ramamoorthy H, Isaac B. Depletion of the cellular antioxidant system contributes to tenofovir disoproxil fumarate - induced mitochondrial damage and increased oxido-nitrosative stress in the kidney.J Biomed Sci. 2013;20:61. [DOI] [PubMed] [PMC]
Zeng Y, Hu R, Ma W, Ding Y, Zhou Y, Peng X, et al. New tricks for old drugs- praziquantel ameliorates bleomycin-induced pulmonary fibrosis in mice.BMC Pharmacol Toxicol. 2024;25:18. [DOI] [PubMed] [PMC]
Zhang G, Liu H, Xue T, Kong X, Tian D, Luo L, et al. Ribavirin extends the lifespan of Caenorhabditis elegans through AMPK-TOR Signaling.Eur J Pharmacol. 2023;946:175548. [DOI] [PubMed]
Lewis W, Dalakas MC. Mitochondrial toxicity of antiviral drugs.Nat Med. 1995;1:417–22. [DOI] [PubMed]
Kondapalli N, Katari V, Dalal KK, Paruchuri S, Thodeti CK. Microbiota in Gut-Heart Axis: Metabolites and Mechanisms in Cardiovascular Disease.Compr Physiol. 2025;15:e70024. [DOI] [PubMed] [PMC]
Li Y, Li C, Zhou Q, Liu X, Qiao Y, Xie T, et al. Multiomics and cellular senescence profiling of aging human skeletal muscle uncovers Maraviroc as a senotherapeutic approach for sarcopenia.Nat Commun. 2025;16:6207. [DOI] [PubMed] [PMC]
Wang X, Zhu Y, Liu H, Wang X, Zhang H, Chen X. Nitazoxanide alleviates experimental pulmonary fibrosis by inhibiting the development of cellular senescence.Life Sci. 2025;361:123302. [DOI] [PubMed]
Cho RL, Shih YL, Lien CF, Huang YJ, Lien PY, Lin CS, et al. Nitroxoline upregulates low-density lipoprotein receptors expression, enhances lipid metabolism, and reduces hepatic steatosis and atherosclerosis in Apoe-/- mice.Biochim Biophys Acta Mol Basis Dis. 2025;1871:168016. [DOI] [PubMed]
Wu R, Sun F, Zhang W, Ren J, Liu GH. Targeting aging and age-related diseases with vaccines.Nat Aging. 2024;4:464–82. [DOI] [PubMed]
Pessoa J, Nóbrega-Pereira S, de Jesus BB. Senescent cell-derived vaccines: a new concept towards an immune response against cancer and aging?Aging (Albany NY). 2024;16:10657–65. [DOI] [PubMed] [PMC]
Allen JC, Toapanta FR, Chen W, Tennant SM. Understanding immunosenescence and its impact on vaccination of older adults.Vaccine. 2020;38:8264–72. [DOI] [PubMed] [PMC]
Hsiao CL, Katsuumi G, Yoshida Y, Furihata T, Joki Y, Furuuchi R, et al. Vaccination targeting senescence-associated transmembrane protein alleviated cardiovascular pathology in the mice.Eur Heart J. 2024;45:ehae666.3654. [DOI]
