Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Targeting aging and age-related diseases with vaccines

Nature Aging volume 4, pages 464–482 (2024)Cite this article

Subjects

Abstract

Aging is a major risk factor for numerous chronic diseases. Vaccination offers a promising strategy to combat these age-related diseases by targeting specific antigens and inducing immune responses. Here, we provide a comprehensive overview of recent advances in vaccine-based interventions targeting these diseases, including Alzheimer’s disease, type II diabetes, hypertension, abdominal aortic aneurysm, atherosclerosis, osteoarthritis, fibrosis and cancer, summarizing current approaches for identifying disease-associated antigens and inducing immune responses against these targets. Further, we reflect on the recent development of vaccines targeting senescent cells, as a strategy for more broadly targeting underlying causes of aging and associated pathologies. In addition to highlighting recent progress in these areas, we discuss important next steps to advance the therapeutic potential of these vaccines, including improving and robustly demonstrating efficacy in human clinical trials, as well as rigorously evaluating the safety and long-term effects of these vaccine strategies.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Timeline of milestones relevant to vaccine technology and senotherapy.
Fig. 2: Vaccine strategies for immunotherapy and prevention of AD.
Fig. 3: Vaccine strategies for immunotherapy and prevention of T2D.
Fig. 4: Vaccine strategies combating age-related vascular pathologies.
Fig. 5: Major cancer vaccine development platforms and immunological mechanisms of cancer vaccines.
Fig. 6: Potential senescent cell antigens for immunotherapy development.

Similar content being viewed by others

References

  1. Lopez-Otin, C., Blasco, M. A., Partridge, L., Serrano, M. & Kroemer, G. Hallmarks of aging: an expanding universe. Cell 186, 243–278 (2023).

    Article  CAS  PubMed  Google Scholar 

  2. Benz, C. C. & Yau, C. Ageing, oxidative stress and cancer: paradigms in parallax. Nat. Rev. Cancer 8, 875–879 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Wu, Z., Qu, J., Zhang, W. & Liu, G. H. Stress, epigenetics, and aging: unraveling the intricate crosstalk. Mol. Cell 84, 34–54 (2024).

    Article  CAS  PubMed  Google Scholar 

  4. Cai, Y. et al. The landscape of aging. Sci. China Life Sci. 65, 2354–2454 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Dehghan, A. et al. Risk of type 2 diabetes attributable to C-reactive protein and other risk factors. Diabetes Care 30, 2695–2699 (2007).

    Article  CAS  PubMed  Google Scholar 

  6. Bussian, T. J. et al. Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline. Nature 562, 578–582 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Yan, H. et al. Degeneration Directory: a multi-omics web resource for degenerative diseases. Protein Cell https://doi.org/10.1093/procel/pwad066 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Katz, D. L. & Meller, S. Can we say what diet is best for health? Annu. Rev. Public Health 35, 83–103 (2014).

    Article  CAS  PubMed  Google Scholar 

  9. Newman, J. C. et al. Ketogenic diet reduces midlife mortality and improves memory in aging mice. Cell Metab. 26, 547–557 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hojman, P., Gehl, J., Christensen, J. F. & Pedersen, B. K. Molecular mechanisms linking exercise to cancer prevention and treatment. Cell Metab. 27, 10–21 (2018).

    Article  CAS  PubMed  Google Scholar 

  11. Harrison, D. E. et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460, 392–395 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Vaiserman, A., De Falco, E., Koliada, A., Maslova, O. & Balistreri, C. R. Anti-ageing gene therapy: not so far away? Ageing Res. Rev. 56, 100977 (2019).

    Article  PubMed  Google Scholar 

  13. Yan, P. et al. FOXO3-engineered human ESC-derived vascular cells promote vascular protection and regeneration. Cell Stem Cell 24, 447–461 (2019).

    Article  CAS  PubMed  Google Scholar 

  14. Liu, F. et al. Identification of FOXO1 as a geroprotector in human synovium through single-nucleus transcriptomic profiling. Protein Cell https://doi.org/10.1093/procel/pwad060 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Huang, D. et al. CRL2APPBP2-mediated TSPYL2 degradation counteracts human mesenchymal stem cell senescence. Sci. China Life Sci. https://doi.org/10.1007/s11427-023-2451-3 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Jing, Y. et al. Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging. Protein Cell 14, 497–512 (2023).

    PubMed  Google Scholar 

  17. Yusheng Cai, Z. J., Si Wang. et al. Genetic enhancement: an avenue to combat aging-related diseases. Life Med. https://doi.org/10.1093/lifemedi/lnac054 (2022).

  18. Rudin, C. M. et al. Phase II study of single-agent navitoclax (ABT-263) and biomarker correlates in patients with relapsed small cell lung cancer. Clin. Cancer Res. 18, 3163–3169 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Riedel, S. Edward Jenner and the history of smallpox and vaccination. Proc. Bayl Univ. Med. Cent. 18, 21–25 (2005).

  20. Thomas, F. Jr & Magill, T. Vaccination of human subjects with virus of human influenza. Proc. Soc. Exp. Biol. Med. 33, 604–606 (1936).

    Article  Google Scholar 

  21. Liu, J. et al. Cancer vaccines as promising immuno-therapeutics: platforms and current progress. J. Hematol. Oncol. 15, 28 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Pulendran, B. & Ahmed, R. Immunological mechanisms of vaccination. Nat. Immunol. 12, 509–517 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Pollard, A. J. & Bijker, E. M. A guide to vaccinology: from basic principles to new developments. Nat. Rev. Immunol. 21, 83–100 (2021).

    Article  CAS  PubMed  Google Scholar 

  24. Jackson, D. A., Symons, R. H. & Berg, P. Biochemical method for inserting new genetic information into DNA of Simian Virus 40: circular SV40 DNA molecules containing lambda phage genes and the galactose operon of Escherichia coli. Proc. Natl Acad. Sci. USA 69, 2904–2909 (1972).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. McAleer, W. J. et al. Human hepatitis B vaccine from recombinant yeast. Nature 307, 178–180 (1984).

    Article  CAS  PubMed  Google Scholar 

  26. Kutzler, M. A. & Weiner, D. B. DNA vaccines: ready for prime time? Nat. Rev. Genet. 9, 776–788 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N. Engl. J. Med. 383, 2603–2615 (2020).

  28. Suda, M. et al. Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice. Nat. Aging 1, 1117–1126 (2021).

    Article  PubMed  Google Scholar 

  29. Aging Biomarker, C. et al. Biomarkers of aging. Sci. China Life Sci. 66, 893–1066 (2023).

    Article  Google Scholar 

  30. Aging Biomarker Consortium; Suo, J. et al. A framework of biomarkers for skeletal aging: a consensus statement by the Aging Biomarker Consortium. Life Med. https://doi.org/10.1093/lifemedi/lnad045 (2023).

  31. Aging Biomarker Consortium; Zhang, L. et al. A framework of biomarkers for vascular aging: a consensus statement by the Aging Biomarker Consortium. Life Med. https://doi.org/10.1093/lifemedi/lnad033 (2023).

  32. Aging Biomarker Consortium et al. A biomarker framework for cardiac aging: the Aging Biomarker Consortium consensus statement. Life Med. https://doi.org/10.1093/lifemedi/lnad035 (2023).

    Article  Google Scholar 

  33. Alcorta, D. A. et al. Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. Proc. Natl Acad. Sci. USA 93, 13742–13747 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lu, H. et al. Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics. Protein Cell https://doi.org/10.1093/procel/pwad063 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Boni-Schnetzler, M. et al. Increased interleukin (IL)-1beta messenger ribonucleic acid expression in beta -cells of individuals with type 2 diabetes and regulation of IL-1beta in human islets by glucose and autostimulation. J. Clin. Endocrinol. Metab. 93, 4065–4074 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  36. Valiukas, Z. et al. Immunotherapies for Alzheimer’s disease—a review. Vaccines https://doi.org/10.3390/vaccines10091527 (2022).

  37. Pecchi, E. et al. Induction of nerve growth factor expression and release by mechanical and inflammatory stimuli in chondrocytes: possible involvement in osteoarthritis pain. Arthritis Res. Ther. 16, R16 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Xia, X., Jiang, Q., McDermott, J. & Han, J. J. Aging and Alzheimer’s disease: Comparison and associations from molecular to system level. Aging Cell 17, e12802 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  39. McDade, E., Llibre-Guerra, J. J., Holtzman, D. M., Morris, J. C. & Bateman, R. J. The informed road map to prevention of Alzheimer disease: a call to arms. Mol. Neurodegener. 16, 49 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Broussard, G. J., Mytar, J., Li, R. C. & Klapstein, G. J. The role of inflammatory processes in Alzheimer’s disease. Inflammopharmacology 20, 109–126 (2012).

    Article  CAS  PubMed  Google Scholar 

  41. Zhang, Y., Chen, H., Li, R., Sterling, K. & Song, W. Amyloid beta-based therapy for Alzheimer’s disease: challenges, successes and future. Signal Transduct. Target. Ther. 8, 248 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ossenkoppele, R., van der Kant, R. & Hansson, O. Tau biomarkers in Alzheimer’s disease: towards implementation in clinical practice and trials. Lancet Neurol. 21, 726–734 (2022).

    Article  CAS  PubMed  Google Scholar 

  43. Yamazaki, Y., Zhao, N., Caulfield, T. R., Liu, C. C. & Bu, G. Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies. Nat. Rev. Neurol. 15, 501–518 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Depp, C. et al. Myelin dysfunction drives amyloid-beta deposition in models of Alzheimer’s disease. Nature 618, 349–357 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Gilman, S. et al. Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology 64, 1553–1562 (2005).

    Article  CAS  PubMed  Google Scholar 

  46. Reiss, A. B. et al. Alzheimer disease clinical trials targeting amyloid: lessons learned from success in mice and failure in humans. Neurologist 26, 52–61 (2021).

    Article  PubMed  Google Scholar 

  47. Ketter, N. et al. A randomized, double-blind, phase 2 study of the effects of the vaccine vanutide cridificar with QS-21 adjuvant on immunogenicity, safety and amyloid imaging in patients with mild to moderate alzheimer’s disease. J. Prev. Alzheimers Dis. 3, 192–201 (2016).

    CAS  PubMed  Google Scholar 

  48. Plascencia-Villa, G. & Perry, G. Lessons from antiamyloid-beta immunotherapies in Alzheimer’s disease. Handb. Clin. Neurol. 193, 267–292 (2023).

    Article  PubMed  Google Scholar 

  49. Hardy, J. & Allsop, D. Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol. Sci. 12, 383–388 (1991).

    Article  CAS  PubMed  Google Scholar 

  50. Muhs, A. et al. Liposomal vaccines with conformation-specific amyloid peptide antigens define immune response and efficacy in APP transgenic mice. Proc. Natl Acad. Sci. USA 104, 9810–9815 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Hickman, D. T. et al. Sequence-independent control of peptide conformation in liposomal vaccines for targeting protein misfolding diseases. J. Biol. Chem. 286, 13966–13976 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Rafii, M. S. et al. Safety, tolerability, and immunogenicity of the ACI-24 vaccine in adults with Down syndrome: a phase 1b randomized clinical trial. JAMA Neurol. 79, 565–574, (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Wang, C. Y. et al. UB-311, a novel UBITh amyloid beta peptide vaccine for mild Alzheimer’s disease. Alzheimers Dement. 3, 262–272 (2017).

    Article  Google Scholar 

  54. Kwan, P., Konno, H., Chan, K. Y. & Baum, L. Rationale for the development of an Alzheimer’s disease vaccine. Hum. Vaccin. Immunother. 16, 645–653 (2020).

    Article  CAS  PubMed  Google Scholar 

  55. Yu, H. J. et al. Safety, tolerability, immunogenicity, and efficacy of UB-311 in participants with mild Alzheimer’s disease: a randomised, double-blind, placebo-controlled, phase 2a study. EBioMedicine 94, 104665 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Petrushina, I. et al. Characterization and preclinical evaluation of the cGMP grade DNA based vaccine, AV-1959D to enter the first-in-human clinical trials. Neurobiol. Dis. 139, 104823 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Davtyan, H. et al. The MultiTEP platform-based Alzheimer’s disease epitope vaccine activates a broad repertoire of T helper cells in nonhuman primates. Alzheimers Dement. 10, 271–283 (2014).

    Article  PubMed  Google Scholar 

  58. Lacosta, A. M. et al. Safety, tolerability and immunogenicity of an active anti-Abeta(40) vaccine (ABvac40) in patients with Alzheimer’s disease: a randomised, double-blind, placebo-controlled, phase I trial. Alzheimers Res. Ther. 10, 12 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  59. Neff, R. A. et al. Molecular subtyping of Alzheimer’s disease using RNA sequencing data reveals novel mechanisms and targets. Sci. Adv. https://doi.org/10.1126/sciadv.abb5398 (2021).

  60. Theunis, C. et al. Efficacy and safety of a liposome-based vaccine against protein Tau, assessed in tau.P301L mice that model tauopathy. PLoS ONE 8, e72301 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Song, C. et al. Immunotherapy for Alzheimer’s disease: targeting beta-amyloid and beyond. Transl. Neurodegener. 11, 18 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Novak, P. et al. FUNDAMANT: an interventional 72-week phase 1 follow-up study of AADvac1, an active immunotherapy against tau protein pathology in Alzheimer’s disease. Alzheimers Res. Ther. 10, 108 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  63. Panza, F. & Logroscino, G. Anti-tau vaccine in Alzheimer’s disease: a tentative step. Lancet Neurol. 16, 99–100 (2017).

    Article  PubMed  Google Scholar 

  64. Novak, P. et al. ADAMANT: a placebo-controlled randomized phase 2 study of AADvac1, an active immunotherapy against pathological tau in Alzheimer’s disease. Nat. Aging 1, 521–534 (2021).

    Article  PubMed  Google Scholar 

  65. Sato, C. et al. Tau kinetics in neurons and the human central nervous system. Neuron 97, 1284–1298 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Park, H. H. et al. Novel vaccine peptide GV1001 effectively blocks beta-amyloid toxicity by mimicking the extra-telomeric functions of human telomerase reverse transcriptase. Neurobiol. Aging 35, 1255–1274 (2014).

    Article  CAS  PubMed  Google Scholar 

  67. Malonis, R. J., Lai, J. R. & Vergnolle, O. Peptide-based vaccines: current progress and future challenges. Chem. Rev. 120, 3210–3229 (2020).

    Article  CAS  PubMed  Google Scholar 

  68. Frenkel, D., Maron, R., Burt, D. S. & Weiner, H. L. Nasal vaccination with a proteosome-based adjuvant and glatiramer acetate clears beta-amyloid in a mouse model of Alzheimer disease. J. Clin. Invest. 115, 2423–2433 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Rafii, M. S. & Aisen, P. S. Detection and treatment of Alzheimer’s disease in its preclinical stage. Nat. Aging 3, 520–531 (2023).

    Article  PubMed  Google Scholar 

  70. Baruch, K. et al. PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer’s disease. Nat. Med. 22, 135–137 (2016).

    Article  CAS  PubMed  Google Scholar 

  71. Ogurtsova, K. et al. IDF Diabetes Atlas: global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res. Clin. Pract. 128, 40–50 (2017).

    Article  CAS  PubMed  Google Scholar 

  72. DeFronzo, R. A. et al. Type 2 diabetes mellitus. Nat. Rev. Dis. Prim. 1, 15019 (2015).

    Article  PubMed  Google Scholar 

  73. Gallwitz, B. Clinical perspectives on the use of the GIP/GLP-1 receptor agonist tirzepatide for the treatment of type-2 diabetes and obesity. Front. Endocrinol. https://doi.org/10.3389/fendo.2022.1004044 (2022).

    Article  Google Scholar 

  74. Vogt, A. S. et al. Anti-IAPP monoclonal antibody improves clinical symptoms in a mouse model of type 2 diabetes. Vaccines https://doi.org/10.3390/vaccines9111316 (2021).

  75. Scarpa, E. S. et al. The combination of natural molecules naringenin, hesperetin, curcumin, polydatin and quercetin synergistically decreases sema3e expression levels and DPPIV activity in in vitro models of insulin resistance. Int. J. Mol. Sci. https://doi.org/10.3390/ijms24098071 (2023).

  76. Voelker, J. et al. Anti-TGF-beta1 antibody therapy in patients with diabetic nephropathy. J. Am. Soc. Nephrol. 28, 953–962 (2017).

    Article  CAS  PubMed  Google Scholar 

  77. Galicia-Garcia, U. et al. Pathophysiology of type 2 diabetes mellitus. Int. J. Mol. Sci. https://doi.org/10.3390/ijms21176275 (2020).

  78. Sandhu, H. et al. Glucagon-like peptide 1 increases insulin sensitivity in depancreatized dogs. Diabetes 48, 1045–1053 (1999).

    Article  CAS  PubMed  Google Scholar 

  79. Pang, Z. et al. Therapeutic vaccine against DPP4 improves glucose metabolism in mice. Proc. Natl Acad. Sci. USA 111, E1256–E1263 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Dinarello, C. A., Simon, A. & van der Meer, J. W. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat. Rev. Drug Discov. 11, 633–652 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Malozowski, S. & Sahlroot, J. T. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N. Engl. J. Med. 357, 302–303 (2007).

    Article  CAS  PubMed  Google Scholar 

  82. Cavelti-Weder, C. et al. Development of an interleukin-1beta vaccine in patients with type 2 diabetes. Mol. Ther. 24, 1003–1012 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Dhimolea, E. Canakinumab. MAbs 2, 3–13 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Zhang, Y. et al. Therapeutic vaccine against IL-1beta improved glucose control in a mouse model of type 2 diabetes. Life Sci. 192, 68–74 (2018).

    Article  CAS  PubMed  Google Scholar 

  85. Ekoru, K. et al. Type 2 diabetes complications and comorbidity in sub-Saharan Africans. EClinicalMedicine 16, 30–41 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  86. Danser, A. H. & Deinum, J. Renin, prorenin and the putative (pro)renin receptor. Hypertension 46, 1069–1076 (2005).

    Article  CAS  PubMed  Google Scholar 

  87. Kanda, A. & Ishida, S. Prorenin receptor: involvement in diabetic retinopathy and development of molecular targeted therapy. J. Diabetes Investig. 10, 6–17 (2019).

    Article  CAS  PubMed  Google Scholar 

  88. Yokota, H. et al. Effect of prorenin peptide vaccine on the early phase of diabetic retinopathy in a murine model of type 2 diabetes. PLoS ONE 17, e0262568 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Abdul-Ghani, M. A. & DeFronzo, R. A. Pathogenesis of insulin resistance in skeletal muscle. J. Biomed. Biotechnol. 2010, 476279 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  90. Shimizu, I. et al. Semaphorin3E-induced inflammation contributes to insulin resistance in dietary obesity. Cell Metab. 18, 491–504 (2013).

    Article  CAS  PubMed  Google Scholar 

  91. Garay-Gutierrez, N. F., Hernandez-Fuentes, C. P., Garcia-Rivas, G., Lavandero, S. & Guerrero-Beltran, C. E. Vaccines against components of the renin–angiotensin system. Heart Fail. Rev. 26, 711–726 (2021).

    Article  CAS  PubMed  Google Scholar 

  92. Downham, M. R. et al. Evaluation of two carrier protein-angiotensin I conjugate vaccines to assess their future potential to control high blood pressure (hypertension) in man. Br. J. Clin. Pharm. 56, 505–512 (2003).

    Article  CAS  Google Scholar 

  93. Ambuhl, P. M. et al. A vaccine for hypertension based on virus-like particles: preclinical efficacy and phase I safety and immunogenicity. J. Hypertens. 25, 63–72 (2007).

    Article  PubMed  Google Scholar 

  94. Tissot, A. C. et al. Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory blood pressure: a double-blind, randomised, placebo-controlled phase IIa study. Lancet 371, 821–827 (2008).

    Article  CAS  PubMed  Google Scholar 

  95. Brown, M. J. Success and failure of vaccines against renin–angiotensin system components. Nat. Rev. Cardiol. 6, 639–647 (2009).

    Article  CAS  PubMed  Google Scholar 

  96. Chen, X. et al. Effectiveness and safety of a therapeutic vaccine against angiotensin II receptor type 1 in hypertensive animals. Hypertension 61, 408–416 (2013).

    Article  CAS  PubMed  Google Scholar 

  97. Zhou, Y. et al. ATRQbeta-001 vaccine prevents atherosclerosis in apolipoprotein E-null mice. J. Hypertens. 34, 474–485 (2016).

    Article  CAS  PubMed  Google Scholar 

  98. Pan, Y. et al. The ATRQbeta-001 vaccine improves cardiac function and prevents postinfarction cardiac remodeling in mice. Hypertens. Res. 42, 329–340 (2019).

    Article  CAS  PubMed  Google Scholar 

  99. Ferrario, C. M. Importance of the renin-angiotensin-aldosterone system (RAS) in the physiology and pathology of hypertension. An overview. Drugs 39, 1–8 (1990).

    Article  PubMed  Google Scholar 

  100. Li, C. et al. Vaccine targeted alpha 1D-adrenergic receptor for hypertension. Hypertension 74, 1551–1562 (2019).

    Article  CAS  PubMed  Google Scholar 

  101. Tanoue, A. et al. The alpha 1D-adrenergic receptor directly regulates arterial blood pressure via vasoconstriction. J. Clin. Invest. 109, 765–775 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Docherty, J. R. Subtypes of functional alpha1-adrenoceptor. Cell. Mol. Life Sci. 67, 405–417 (2010).

    Article  CAS  PubMed  Google Scholar 

  103. Nordon, I. M., Hinchliffe, R. J., Loftus, I. M. & Thompson, M. M. Pathophysiology and epidemiology of abdominal aortic aneurysms. Nat. Rev. Cardiol. 8, 92–102 (2011).

    Article  PubMed  Google Scholar 

  104. Greenhalgh, R. M. et al. Early elective open surgical repair of small abdominal aortic aneurysms is not recommended: results of the UK Small Aneurysm Trial. Steering Committee. Eur. J. Vasc. Endovasc. Surg. 16, 462–464 (1998).

    Article  CAS  PubMed  Google Scholar 

  105. Kurashiki, T., Miyake, T., Nakagami, H., Nishimura, M. & Morishita, R. Prevention of progression of aortic aneurysm by peptide vaccine against Ang II (angiotensin II) in a rat model. Hypertension 76, 1879–1888 (2020).

    Article  CAS  PubMed  Google Scholar 

  106. Xuan, H. et al. Inhibition or deletion of angiotensin II type 1 receptor suppresses elastase-induced experimental abdominal aortic aneurysms. J. Vasc. Surg. 67, 573–584 (2018).

    Article  PubMed  Google Scholar 

  107. Zhang, H. et al. ATRQbeta-001 vaccine prevents experimental abdominal aortic aneurysms. J. Am. Heart Assoc. 8, e012341 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  108. Wang, J. C. & Bennett, M. Aging and atherosclerosis: mechanisms, functional consequences, and potential therapeutics for cellular senescence. Circ. Res. 111, 245–259 (2012).

    Article  CAS  PubMed  Google Scholar 

  109. Kobiyama, K. & Ley, K. Atherosclerosis. Circ. Res. 123, 1118–1120 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Hansson, G. K. & Nilsson, J. Developing a vaccine against atherosclerosis. Nat. Rev. Cardiol. 17, 451–452 (2020).

    Article  PubMed  Google Scholar 

  111. Ait-Oufella, H. et al. Natural regulatory T cells control the development of atherosclerosis in mice. Nat. Med. 12, 178–180 (2006).

    Article  CAS  PubMed  Google Scholar 

  112. Gistera, A. et al. Low-density lipoprotein-reactive T cells regulate plasma cholesterol levels and development of atherosclerosis in humanized hypercholesterolemic mice. Circulation 138, 2513–2526 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Lichtman, A. H., Binder, C. J., Tsimikas, S. & Witztum, J. L. Adaptive immunity in atherogenesis: new insights and therapeutic approaches. J. Clin. Invest. 123, 27–36 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Kimura, T. et al. Regulatory CD4+ T cells recognize major histocompatibility complex class II molecule-restricted peptide epitopes of apolipoprotein B. Circulation 138, 1130–1143 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Momtazi-Borojeni, A. A., Jaafari, M. R., Badiee, A. & Sahebkar, A. Long-term generation of antiPCSK9 antibody using a nanoliposome-based vaccine delivery system. Atherosclerosis 283, 69–78 (2019).

    Article  CAS  PubMed  Google Scholar 

  116. Ma, Z. et al. Peptide vaccine against ADAMTS-7 ameliorates atherosclerosis and postinjury neointima hyperplasia. Circulation 147, 728–742 (2023).

    Article  CAS  PubMed  Google Scholar 

  117. Bourinbaiar, A. S. & Jirathitikal, V. Effect of oral immunization with pooled antigens derived from adipose tissue on atherosclerosis and obesity indices. Vaccine 28, 2763–2768 (2010).

    Article  CAS  PubMed  Google Scholar 

  118. Bourinbaiar, A. S. & Jirathitikal, V. Safety and efficacy trial of adipose-tissue derived oral preparation V-6 Immunitor (V-6): results of open-label, two-month, follow-up study. Lipids Health Dis. 9, 14 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  119. Nilsson, J. & Hansson, G. K. Vaccination strategies and immune modulation of atherosclerosis. Circ. Res. 126, 1281–1296 (2020).

    Article  CAS  PubMed  Google Scholar 

  120. Ridker, P. M. et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med. 377, 1119–1131 (2017).

    Article  CAS  PubMed  Google Scholar 

  121. Loeser, R. F. The role of aging in the development of osteoarthritis. Trans. Am. Clin. Climatol. Assoc. 128, 44–54 (2017).

    PubMed  PubMed Central  Google Scholar 

  122. Shane Anderson, A. & Loeser, R. F. Why is osteoarthritis an age-related disease? Best. Pract. Res Clin. Rheumatol. 24, 15–26 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. von Loga, I. S. et al. Active immunisation targeting nerve growth factor attenuates chronic pain behaviour in murine osteoarthritis. Ann. Rheum. Dis. 78, 672–675 (2019).

    Article  Google Scholar 

  124. Lane, N. E. & Corr, M. Osteoarthritis in 2016: anti-NGF treatments for pain—two steps forward, one step back? Nat. Rev. Rheumatol. 13, 76–78 (2017).

    Article  PubMed  Google Scholar 

  125. Chen, Y. et al. Aging reprograms the hematopoietic-vascular niche to impede regeneration and promote fibrosis. Cell Metab. 33, 395–410 (2021).

    Article  CAS  PubMed  Google Scholar 

  126. Brack, A. S. et al. Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science 317, 807–810 (2007).

    Article  CAS  PubMed  Google Scholar 

  127. Sobecki, M. et al. Vaccination-based immunotherapy to target profibrotic cells in liver and lung. Cell Stem Cell 29, 1459–1474 (2022).

    Article  CAS  PubMed  Google Scholar 

  128. Kang, H. M. et al. Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development. Nat. Med. 21, 37–46 (2015).

    Article  CAS  PubMed  Google Scholar 

  129. Wu, D. et al. Vaccine against PCSK9 improved renal fibrosis by regulating fatty acid beta-oxidation. J. Am. Heart Assoc. 9, e014358 (2020).

    Article  CAS  PubMed  Google Scholar 

  130. Melero, I. et al. Therapeutic vaccines for cancer: an overview of clinical trials. Nat. Rev. Clin. Oncol. 11, 509–524 (2014).

    Article  CAS  PubMed  Google Scholar 

  131. Markowitz, L. E. et al. Human papillomavirus vaccine introduction—the first five years. Vaccine 30, 139–148, (2012).

    Article  Google Scholar 

  132. Crews, D. W., Dombroski, J. A. & King, M. R. Prophylactic cancer vaccines engineered to elicit specific adaptive immune response. Front. Oncol. 11, 626463 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Karpanen, T. & Olweus, J. The potential of donor T-cell repertoires in neoantigen-targeted cancer immunotherapy. Front. Immunol. 8, 1718 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  134. Paston, S. J., Brentville, V. A., Symonds, P. & Durrant, L. G. Cancer vaccines, adjuvants, and delivery systems. Front. Immunol. 12, 627932 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Giaccone, G. et al. A phase III study of belagenpumatucel-L, an allogeneic tumour cell vaccine, as maintenance therapy for non-small cell lung cancer. Eur. J. Cancer 51, 2321–2329 (2015).

    Article  CAS  PubMed  Google Scholar 

  136. Verma, V. et al. PD-1 blockade in subprimed CD8 cells induces dysfunctional PD-1+CD38hi cells and anti-PD-1 resistance. Nat. Immunol. 20, 1231–1243 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Saxena, M., van der Burg, S. H., Melief, C. J. M. & Bhardwaj, N. Therapeutic cancer vaccines. Nat. Rev. Cancer 21, 360–378 (2021).

    Article  CAS  PubMed  Google Scholar 

  138. Lazaro, A. et al. Human leukocyte antigen (HLA) typing by DNA sequencing. Methods Mol. Biol. 1034, 161–195 (2013).

    Article  CAS  PubMed  Google Scholar 

  139. Jennings, L. J. et al. Guidelines for validation of next-generation sequencing-based oncology panels: a joint consensus recommendation of the association for molecular pathology and college of american pathologists. J. Mol. Diagn. 19, 341–365 (2017).

    Article  PubMed  Google Scholar 

  140. Duperret, E. K. et al. A Synthetic DNA, multi-neoantigen vaccine drives predominately MHC class I CD8+ T-cell responses, impacting tumor challenge. Cancer Immunol. Res. 7, 174–182 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Liu, S. et al. A DNA nanodevice-based vaccine for cancer immunotherapy. Nat. Mater. 20, 421–430 (2021).

    Article  CAS  PubMed  Google Scholar 

  142. Hammerich, L., Bhardwaj, N., Kohrt, H. E. & Brody, J. D. In situ vaccination for the treatment of cancer. Immunotherapy 8, 315–330 (2016).

    Article  CAS  PubMed  Google Scholar 

  143. Chen, J. et al. In situ cancer vaccination using lipidoid nanoparticles. Sci. Adv. 7, eadv.abf1244 (2021).

  144. Chen, L. et al. Bacterial cytoplasmic membranes synergistically enhance the antitumor activity of autologous cancer vaccines. Sci. Transl. Med. https://doi.org/10.1126/scitranslmed.abc2816 (2021).

  145. Lopez-Otin, C., Pietrocola, F., Roiz-Valle, D., Galluzzi, L. & Kroemer, G. Meta-hallmarks of aging and cancer. Cell Metab. 35, 12–35 (2023).

    Article  CAS  PubMed  Google Scholar 

  146. Wells, D. K. et al. Key parameters of tumor epitope immunogenicity revealed through a consortium approach improve neoantigen prediction. Cell 183, 818–834 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Liu, X. et al. Resurrection of endogenous retroviruses during aging reinforces senescence. Cell 186, 287–304 (2023).

    Article  CAS  PubMed  Google Scholar 

  148. Xiaoqian Liu, H. J. et al. Migrasomes trigger innate immune activation and mediate transmission of senescence signals across human cells. Life Med. https://doi.org/10.1093/lifemedi/lnad050 (2023).

  149. Marin, I. et al. Cellular senescence is immunogenic and promotes antitumor immunity. Cancer Discov. 13, 410–431 (2023).

    Article  CAS  PubMed  Google Scholar 

  150. Sciorati, C. et al. Pharmacological blockade of TNF prevents sarcopenia and prolongs survival in aging mice. Aging 12, 23497–23508 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Ridker, P. M. et al. Effect of interleukin-1beta inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet 390, 1833–1842 (2017).

    Article  CAS  PubMed  Google Scholar 

  152. Kang, T. W. et al. Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature 479, 547–551 (2011).

    Article  CAS  PubMed  Google Scholar 

  153. Chen, H. A. et al. Senescence rewires microenvironment sensing to facilitate antitumor immunity. Cancer Discov. 13, 432–453 (2023).

    Article  CAS  PubMed  Google Scholar 

  154. Childs, B. G. et al. Senescent cells: an emerging target for diseases of ageing. Nat. Rev. Drug Discov. 16, 718–735 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Childs, B. G. et al. Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science 354, 472–477 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Jeon, O. H. et al. Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment. Nat. Med. 23, 775–781 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Baker, D. J. et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479, 232–236 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Baker, D. J. et al. Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature 530, 184–189 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Xue, W. et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445, 656–660 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Yoshida, S. et al. The CD153 vaccine is a senotherapeutic option for preventing the accumulation of senescent T cells in mice. Nat. Commun. 11, 2482 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Sharpless, N. E., Ramsey, M. R., Balasubramanian, P., Castrillon, D. H. & DePinho, R. A. The differential impact of p16INK4a or p19ARF deficiency on cell growth and tumorigenesis. Oncogene 23, 379–385 (2004).

    Article  CAS  PubMed  Google Scholar 

  162. Xu, W. & Larbi, A. Markers of T cell senescence in humans. Int. J. Mol. Sci. https://doi.org/10.3390/ijms18081742 (2017).

  163. Mittelbrunn, M. & Kroemer, G. Hallmarks of T cell aging. Nat. Immunol. 22, 687–698 (2021).

    Article  CAS  PubMed  Google Scholar 

  164. Shirakawa, K. et al. Obesity accelerates T cell senescence in murine visceral adipose tissue. J. Clin. Invest. 126, 4626–4639 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  165. Smith, C. A. et al. CD30 antigen, a marker for Hodgkin’s lymphoma, is a receptor whose ligand defines an emerging family of cytokines with homology to TNF. Cell 73, 1349–1360 (1993).

    Article  CAS  PubMed  Google Scholar 

  166. Blazar, B. R. et al. CD30/CD30 ligand (CD153) interaction regulates CD4+ T cell-mediated graft-versus-host disease. J. Immunol. 173, 2933–2941 (2004).

    Article  CAS  PubMed  Google Scholar 

  167. Sato, Y. et al. CD153/CD30 signaling promotes age-dependent tertiary lymphoid tissue expansion and kidney injury. J. Clin. Invest. https://doi.org/10.1172/JCI146071 (2022).

  168. Yazdanbakhsh, M., Kremsner, P. G. & van Ree, R. Allergy, parasites, and the hygiene hypothesis. Science 296, 490–494 (2002).

    Article  CAS  PubMed  Google Scholar 

  169. Hansen, G., Berry, G., DeKruyff, R. H. & Umetsu, D. T. Allergen-specific Th1 cells fail to counterbalance Th2 cell-induced airway hyperreactivity but cause severe airway inflammation. J. Clin. Invest. 103, 175–183 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Sallin, M. A. et al. Host resistance to pulmonary Mycobacterium tuberculosis infection requires CD153 expression. Nat. Microbiol. 3, 1198–1205 (2018).

    Article  CAS  PubMed  Google Scholar 

  171. Vanhoutte, P. M. Endothelial dysfunction and atherosclerosis. Eur. Heart J. 18, E19–E29 (1997).

    Article  PubMed  Google Scholar 

  172. Suda, M. et al. Glycoprotein nonmetastatic melanoma protein B regulates lysosomal integrity and lifespan of senescent cells. Sci. Rep. 12, 6522 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Ogawa, T. et al. Osteoactivin upregulates expression of MMP-3 and MMP-9 in fibroblasts infiltrated into denervated skeletal muscle in mice. Am. J. Physiol. Cell Physiol. 289, 697–707 (2005).

    Article  Google Scholar 

  174. Saade, M., Araujo de Souza, G., Scavone, C. & Kinoshita, P. F. The role of GPNMB in inflammation. Front. Immunol. 12, 674739 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Demaria, M. et al. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev. Cell 31, 722–733 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Hernandez-Segura, A. et al. Unmasking transcriptional heterogeneity in senescent cells. Curr. Biol. 27, 2652–2660 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Van Damme, H. et al. Therapeutic depletion of CCR8+ tumor-infiltrating regulatory T cells elicits antitumor immunity and synergizes with anti-PD-1 therapy. J. Immunother. Cancer https://doi.org/10.1136/jitc-2020-001749 (2021).

  178. Amor, C. et al. Senolytic CAR T cells reverse senescence-associated pathologies. Nature 583, 127–132 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Amor, C. et al. Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction. Nat. Aging https://doi.org/10.1038/s43587-023-00560-5 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  180. Grove, L. M. et al. Urokinase-type plasminogen activator receptor (uPAR) ligation induces a raft-localized integrin signaling switch that mediates the hypermotile phenotype of fibrotic fibroblasts. J. Biol. Chem. 289, 12791–12804 (2014).

  181. Elberling, C. et al. Urokinase receptor forms in serum from non-small cell lung cancer patients: relation to prognosis. Lung Cancer 74, 510–515 (2011).

  182. Li, Y. & Cozzi, P. J. Targeting uPA/uPAR in prostate cancer. Cancer Treatment Rev. 33, 521–527, (2007).

    Article  CAS  Google Scholar 

  183. Kiyan, J., Smith, G., Haller, H. & Dumler, I. Urokinase-receptor-mediated phenotypic changes in vascular smooth muscle cells require the involvement of membrane rafts. Biochem. J. 423, 343–351 (2009).

    Article  CAS  PubMed  Google Scholar 

  184. Bajou, K. et al. Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization. Nat. Med. 4, 923–928 (1998).

    Article  CAS  PubMed  Google Scholar 

  185. Sagiv, A. et al. NKG2D ligands mediate immunosurveillance of senescent cells. Aging 8, 328–344 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Yang, D. et al. NKG2D-CAR T cells eliminate senescent cells in aged mice and nonhuman primates. Sci. Transl. Med. 15, eadd1951 (2023).

    Article  CAS  PubMed  Google Scholar 

  187. Michieletto, D., Lusic, M., Marenduzzo, D. & Orlandini, E. Physical principles of retroviral integration in the human genome. Nat. Commun. 10, 575 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Melenhorst, J. J. et al. Decade-long leukaemia remissions with persistence of CD4+ CAR T cells. Nature 602, 503–509 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Hasegawa, T. et al. Cytotoxic CD4+ T cells eliminate senescent cells by targeting cytomegalovirus antigen. Cell 186, 1417–1431 (2023).

    Article  CAS  PubMed  Google Scholar 

  190. Gasek, N. S., Kuchel, G. A., Kirkland, J. L. & Xu, M. Strategies for targeting senescent cells in human disease. Nat. Aging 1, 870–879 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  191. Wang, T. W. et al. Blocking PD-L1–PD-1 improves senescence surveillance and ageing phenotypes. Nature 611, 358–364 (2022).

    Article  CAS  PubMed  Google Scholar 

  192. Lin, M. J. et al. Cancer vaccines: the next immunotherapy frontier. Nat. Cancer 3, 911–926 (2022).

    Article  CAS  PubMed  Google Scholar 

  193. Kim, K. M. et al. Identification of senescent cell surface targetable protein DPP4. Genes Dev. 31, 1529–1534 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  194. Ambrosi, T. H. et al. Adipocyte accumulation in the bone marrow during obesity and aging impairs stem cell-based hematopoietic and bone regeneration. Cell Stem Cell 20, 771–784 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Valencia, I. et al. DPP4 promotes human endothelial cell senescence and dysfunction via the PAR2–COX-2–TP axis and NLRP3 inflammasome activation. Hypertension 79, 1361–1373 (2022).

    Article  CAS  PubMed  Google Scholar 

  196. Tian, X. L. & Li, Y. Endothelial cell senescence and age-related vascular diseases. J. Genet Genomics 41, 485–495 (2014).

    Article  PubMed  Google Scholar 

  197. Mund, A. et al. Deep Visual Proteomics defines single-cell identity and heterogeneity. Nat. Biotechnol. 40, 1231–1240 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Li, S. et al. Multiregional profiling of the brain transmembrane proteome uncovers novel regulators of depression. Sci. Adv. https://doi.org/10.1126/sciadv.abf0634 (2021).

  199. Schmidt, J. et al. Prediction of neo-epitope immunogenicity reveals TCR recognition determinants and provides insight into immunoediting. Cell Rep. Med. 2, 100194 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Sohail, M. S., Ahmed, S. F., Quadeer, A. A. & McKay, M. R. In silico T cell epitope identification for SARS-CoV-2: progress and perspectives. Adv. Drug Deliv. Rev. 171, 29–47 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Chiang, E. Y. et al. Targeted depletion of lymphotoxin-alpha-expressing TH1 and TH17 cells inhibits autoimmune disease. Nat. Med. 15, 766–773 (2009).

    Article  CAS  PubMed  Google Scholar 

  202. O’Connor, R. A. et al. Cutting edge: Th1 cells facilitate the entry of Th17 cells to the central nervous system during experimental autoimmune encephalomyelitis. J. Immunol. 181, 3750–3754 (2008).

    Article  PubMed  Google Scholar 

  203. Liu, Z. et al. Immunosenescence: molecular mechanisms and diseases. Signal Transduct. Target. Ther. 8, 200 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Goronzy, J. J. & Weyand, C. M. Understanding immunosenescence to improve responses to vaccines. Nat. Immunol. 14, 428–436 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Pera, A. et al. Immunosenescence: implications for response to infection and vaccination in older people. Maturitas 82, 50–55 (2015).

    Article  CAS  PubMed  Google Scholar 

  206. Weinberger, B. Adjuvant strategies to improve vaccination of the elderly population. Curr. Opin. Pharmacol. 41, 34–41 (2018).

    Article  CAS  PubMed  Google Scholar 

  207. Mannick, J. B. et al. TORC1 inhibition enhances immune function and reduces infections in the elderly. Sci. Transl. Med. https://doi.org/10.1126/scitranslmed.aaq1564 (2018).

  208. Akinc, A. et al. Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms. Mol. Ther. 18, 1357–1364 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Pardi, N., Hogan, M. J., Porter, F. W. & Weissman, D. mRNA vaccines - a new era in vaccinology. Nat. Rev. Drug Discov. 17, 261–279 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Krizhanovsky, V. et al. Senescence of activated stellate cells limits liver fibrosis. Cell 134, 657–667 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  211. Meyer, K., Hodwin, B., Ramanujam, D., Engelhardt, S. & Sarikas, A. Essential role for premature senescence of myofibroblasts in myocardial fibrosis. J. Am. Coll. Cardiol. 67, 2018–2028 (2016).

    Article  CAS  PubMed  Google Scholar 

  212. Ritschka, B. et al. The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration. Genes Dev. 31, 172–183 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  213. Jun, J. I. & Lau, L. F. The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing. Nat. Cell Biol. 12, 676–685 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Grosse, L. et al. Defined p16high senescent cell types are indispensable for mouse healthspan. Cell Metab. 32, 87–99 (2020).

    Article  CAS  PubMed  Google Scholar 

  215. Cai, Y. et al. Decoding aging-dependent regenerative decline across tissues at single-cell resolution. Cell Stem Cell 30, 1674–1691 (2023).

    Article  CAS  PubMed  Google Scholar 

  216. Cullen, N. C. et al. Efficacy assessment of an active tau immunotherapy in Alzheimer’s disease patients with amyloid and tau pathology: a post hoc analysis of the “ADAMANT” randomised placebo-controlled double-blind multi-centre phase 2 clinical trial. eBioMedicine 99, 104923 (2024).

Download references

Acknowledgements

We are grateful to Z. Wu for providing critical advice for this Review, and L. Bai for her administrative assistance. This work was supported by the National Natural Science Foundation of China (81921006 to G.-H.L., 92149301 to G.-H.L.), the National Key Research and Development Program of China (2020YFA0804000 to G.-H.L., 2020YFA0803401 to J.R., 2022YFA1103700 to W.Z. and 2019YFA0802202 to J.R.), the National Natural Science Foundation of China (92168201 to G.-H.L., 92049116 to W.Z., 32121001 to W.Z. and J.R., and 31970597 to J.R.), the Strategic Priority Research Program of the Chinese Academy of Science (XDB0570100 to J.R.), the CAS Project for Young Scientists in Basic Research (YSBR-076 to G.-H.L. and J.R., YSBR-012 to W.Z.) and the New Cornerstone Science Foundation through the XPLORER PRIZE (2021-1045 to G.-H.L.). All figures were created with or modified from BioRender.com.

Author information

Author notes

  1. These authors contributed equally: Ruochen Wu, Fei Sun.

Authors and Affiliations

  1. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China

    Ruochen Wu & Guang-Hui Liu

  2. Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China

    Ruochen Wu & Guang-Hui Liu

  3. University of Chinese Academy of Sciences, Beijing, China

    Ruochen Wu, Weiqi Zhang, Jie Ren & Guang-Hui Liu

  4. Department of Cell Biology, Duke University Medical Center, Durham, NC, USA

    Fei Sun

  5. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China

    Weiqi Zhang, Jie Ren & Guang-Hui Liu

  6. CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing, China

    Weiqi Zhang & Jie Ren

  7. Sino-Danish College, School of Future Technology, University of Chinese Academy of Sciences, Beijing, China

    Weiqi Zhang & Jie Ren

  8. Aging Biomarker Consortium, Beijing, China

    Weiqi Zhang, Jie Ren & Guang-Hui Liu

  9. Key Laboratory of RNA Science and Engineering, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China

    Jie Ren

  10. Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China

    Guang-Hui Liu

  11. Advanced Innovation Center for Human Brain Protection, and National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital, Capital Medical University, Beijing, China

    Guang-Hui Liu

  12. Aging Translational Medicine Center, International Center for Aging and Cancer, Xuanwu Hospital, Capital Medical University, Beijing, China

    Guang-Hui Liu

Authors
  1. Ruochen Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fei Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Weiqi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jie Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Guang-Hui Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

G.-H.L., J.R. and W.Z. designed and supervised the review and reviewed the manuscript; R.W. and F.S. wrote the manuscript and constructed the figures and tables. All the authors read and approved the article.

Corresponding authors

Correspondence to Weiqi Zhang, Jie Ren or Guang-Hui Liu.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Aging thanks Tohru Minamino and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, R., Sun, F., Zhang, W. et al. Targeting aging and age-related diseases with vaccines. Nat Aging 4, 464–482 (2024). https://doi.org/10.1038/s43587-024-00597-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s43587-024-00597-0

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing