The DOI matches its Crossref record; 117 of the 117 references it cites were found in a registry or an index.
Understanding immunosenescence to improve responses to vaccines
Open accessAbstract
In the older adult, the benefits of vaccination to prevent infectious disease are limited, mainly because of the adaptive immune system's inability to generate protective immunity. The age-dependent decrease in immunological competence, often referred to as 'immunosenescence', results from the progressive deterioration of innate and adaptive immune responses. Most insights into mechanisms of immunological aging have been derived from studies of mouse models. In this Review, we explore how well such models are applicable to understanding the aging process throughout the 80-100 years of human life and discuss recent advances in identifying and characterizing the mechanisms that underlie age-associated defective adaptive immunity in humans.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“These and other models, for which it has been shown that accelerated aging depends, at least partly, on cellular senescence, are valuable for studying the impact of senescence on health and lifespan”
From Guidelines for minimal information on cellular senescence experimentation in vivo (2024) · cites this paper as [100]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Mouse models of rapid telomere shortening, dysfunctional mitosis or impaired DNA repair (Terc, BubR1, and Ercc1 mutant mice, respectively), display high levels of cellular senescence and accelerated aging86,99,100.”
From Guidelines for minimal information on cellular senescence experimentation in vivo (2024) · cites this paper as [100]
Experimental — accuracy not yet measuredIn the citing paper
“Evidence of waning adaptive immunity is already apparent in mid adulthood, as early as at the age of 50 years, with increasing clinical relevance in the 7th–10th decade of life”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Goronzy and Weyand, 2013
In the citing paper
“Mechanistically, immunosenescence is only partially explained by organismal and cellular senescence.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [23]
In the citing paper
“Therefore, these hallmarks of immunosenescence would be markedly affected by the history of the individual exposure to pathogens (6, 23).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [23]
In the citing paper
“The hallmarks of immunosenescence include: (i) a reduced ability to respond to new antigens; (ii) the accumulation of memory T cells; (iii) a lingering level of low-grade inflammation termed “inflamm-aging.””
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [23]
In the citing paper
“T cell clones specific for HCMV dominate the repertoire in the older people and contribute to the contraction in diversity in the memory compartment (23).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [23]
In the citing paper
“In contrast, high frequencies of antigen-specific T cells reactive to HCMV persist throughout life.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [23]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Wherry, E. J. (2011) · Nature Immunology · doi:10.1038/ni.2035 · Cited by 4,062
Of Mice and Not Men: Differences between Mouse and Human Immunology
Mestas, J., & Hughes, C. C. W. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.5.2731 · Cited by 3,822
The PD‐1 pathway in tolerance and autoimmunity
Francisco, L. M., Sage, P. T., & Sharpe, A. H. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00923.x · Cited by 2,300
Vaccine Adjuvants: Putting Innate Immunity to Work
Coffman, R. L., Sher, A., & Seder, R. A. (2010) · Immunity · doi:10.1016/j.immuni.2010.10.002 · Cited by 1,927
Changes in thymic function with age and during the treatment of HIV infection
Douek, D. C., McFarland, R. D., Keiser, P. H., Gage, E. A., Massey, J. M., Haynes, B. F., Polis, M. A., Haase, A. T., Feinberg, M. B., Sullivan#, J. L., et al. (1998) · Nature · doi:10.1038/25374 · Cited by 1,893
Metabolic Regulation of T Lymphocytes
MacIver, N. J., Michalek, R. D., & Rathmell, J. C. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-095956 · Cited by 1,244
Age-related changes in lymphocyte development and function
Linton, P. J., & Dorshkind, K. A. (2004) · Nature Immunology · doi:10.1038/ni1033 · Cited by 1,199
miR-181a Is an Intrinsic Modulator of T Cell Sensitivity and Selection
Li, Q.-J., Chau, J., Ebert, P. J. R., Sylvester, G., Min, H., Liu, G., Braich, R. S., Manoharan, M., Soutschek, J., Skare, P., et al. (2007) · Cell · doi:10.1016/j.cell.2007.03.008 · Cited by 1,165
Redefining Chronic Viral Infection
Virgin, H. W., Wherry, E. J., & Ahmed, R. (2009) · Cell · doi:10.1016/j.cell.2009.06.036 · Cited by 1,031
Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age
Pang, W. W., Price, E. A., Sahoo, D., Beerman, I., Maloney, W. J., Rossi, D. J., Schrier, S. L., & Weissman, I. L. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1116110108 · Cited by 991
Flagged first, then by citations
Research works printed but not linked: 1
- Boraschi, D. et al. Ageing and Immunity. Sci. Transl. Med. (in the press).
Cited by
Sorted by citations
Items 201–300 of 841
Thyagarajan, B., Faul, J. D., Vivek, S., Kim, J. K., Nikolich‐Žugich, J., Weir, D. R., & Crimmins, E. M. (2021) · The Journals of Gerontology Series A · doi:10.1093/gerona/glab300 · Cited by 53
Age-Associated Failure To Adjust Type I IFN Receptor Signaling Thresholds after T Cell Activation
Li, G., Ju, J., Weyand, C. M., & Goronzy, J. J. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1402389 · Cited by 55
“A better understanding of the age-associated defects in adaptive immunity holds the potential to design age-targeted interventions to improve vaccine responses (3, 18).”
BackgroundSelf-citationBektas, A., Zhang, Y., Lehmann, E., Wood, W. H., Becker, K. G., Madara, K., Ferrucci, L., & Sen, R. (2014) · Aging · doi:10.18632/aging.100705 · Cited by 54
Papadatou, I., Tzovara, I., & Licciardi, P. V. (2019) · Vaccines · doi:10.3390/vaccines7010013 · Cited by 52
“Age-driven immunosenescence [57] as well as immunocompromising conditions, such as HIV and asplenia, also diminish the MBC response in comparison to healthy young adults [58–60].”
BackgroundBoikos, C., Fischer, L., O’Brien, D., Vasey, J., Sylvester, G. C., & Mansi, J. A. (2021) · Clinical Infectious Diseases · doi:10.1093/cid/ciab152 · Cited by 52
“Because of immunosenescence, or age-related decline in immune efficacy, older adults have diminished responses to vaccination and are more susceptible to infections and influenza-related sequelae [1, 2].”
BackgroundA Single Cell Transcriptomic Atlas Characterizes Aging Tissues in the MousePreprint
Pisco, A. O., McGeever, A., Schaum, N., Karkanias, J., Neff, N. F., Darmanis, S., Wyss‐Coray, T., & Quake, S. R. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/661728 · Cited by 57
DUSP4-mediated accelerated T-cell senescence in idiopathic CD4 lymphopenia
Bignon, A., Régent, A., Klipfel, L., Desnoyer, A., de la Grange, P., Martinez, V., Lortholary, O., Dalloul, A., Mouthon, L., & Balabanian, K. (2015) · Blood · doi:10.1182/blood-2014-08-598565 · Cited by 51
“EM 151 (92-245) 167 (102-258) 102 (56-257) 64 (42-112)**†”
InfluentialDieleman, J. M., Peelen, L. M., Coulson, T. G., Tran, T., Reid, C. M., Smith, J. A., Myles, P. S., & Pilcher, D. V. (2017) · British Journal of Anaesthesia · doi:10.1093/bja/aex239 · Cited by 52
Denk, D., Singh, A., Kasler, H. G., D’Amico, D., Rey, J., Alcober-Boquet, L., Gorol, J. M., Steup, C., Tiwari, R., Kwok, R., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00996-x · Cited by 58
CD4 T cell defects in the aged: Causes, consequences and strategies to circumvent
Zhang, W., Brahmakshatriya, V., & Swain, S. L. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.01.002 · Cited by 49
“It seems reasonable to conclude from observations of others (Goronzy and Weyand, 2013) and our studies of IL-6 signaling in aged naïve CD4 T cells that the aged T cells have a higher activation threshold, or as in our studies require a higher dose of inflammatory cytokine, compared to those from the young.”
ResultAvian Influenza Viruses, Inflammation, and CD8+ T Cell Immunity
Wang, Z., Loh, L., Kedzierski, Ł., & Kedzierska, K. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00060 · Cited by 52
The life cycle of a T cell after vaccination – where does immune ageing strike?
Kim, C., Fang, F., Weyand, C. M., & Goronzy, J. J. (2016) · Clinical & Experimental Immunology · doi:10.1111/cei.12829 · Cited by 50
Self-citationSingle-cell sequencing reveals antitumor characteristics of intratumoral immune cells in old mice
Zhang, C., Lei, L., Yang, X., Ma, K., Zheng, H., Su, Y., Jiao, A., Wang, X., Liu, H., Zou, Y., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-002809 · Cited by 50
Marciani, D. J. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13608 · Cited by 48
Mu, W., Vanhoosier, E., Elks, C. M., & Grant, R. W. (2018) · Nutrients · doi:10.3390/nu10070918 · Cited by 48
Immune response to Propionibacterium acnes in patients with sarcoidosis – in vivo and in vitro
Schupp, J. C., Tchaptchet, S., Lützen, N., Engelhard, P., Müller–Quernheim, J., Freudenberg, M. A., & Prasse, A. (2015) · BMC Pulmonary Medicine · doi:10.1186/s12890-015-0070-7 · Cited by 47
“, the reactivity to antigens is markedly reduced in older people [35].”
BackgroundDefects in Antiviral T Cell Responses Inflicted by Aging-Associated miR-181a Deficiency
Kim, C., Jadhav, R. R., Gustafson, C. E., Smithey, M. J., Hirsch, A. J., Uhrlaub, J. L., Hildebrand, W. H., Nikolich‐Žugich, J., Weyand, C. M., & Goronzy, J. J. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.10.044 · Cited by 47
“Since miR-181a targets several phosphatases that attenuate TCR signaling, the age-associated decline has been implicated in rendering aged T cells less responsive to antigenic stimulation (Goronzy and Weyand, 2013).”
BackgroundSelf-citationBeran, J., Reynales, H., Põder, A., Yu, C. Y., Pitisuttithum, P., Yuan, L. L., Vermeulen, W., Verhoeven, C., Leav, B. A., Zhang, B., et al. (2021) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(20)30694-0 · Cited by 47
Dynamics of thymus function and T cell receptor repertoire breadth in health and disease
Granadier, D., Iovino, L., Kinsella, S. M., & Dudakov, J. A. (2021) · Seminars in Immunopathology · doi:10.1007/s00281-021-00840-5 · Cited by 46
Davtyan, H., Zagorski, K., Rajapaksha, H., Hovakimyan, A., Davtyan, A., Petrushina, I., Kazarian, K., Cribbs, D. H., Petrovsky, N., Agadjanyan, M. G., et al. (2016) · Scientific Reports · doi:10.1038/srep28912 · Cited by 47
Covre, L. P., Martins, R. F., Devine, O., Chambers, E. S., Vukmanovic‐Stejic, M., Silva, J. A., Dietze, R., Rodrigues, R. R., Guedes, H. L. D. M., Falqueto, A., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2018.03001 · Cited by 48
“These include decreased responsiveness to TCR stimulation, diminished proliferative capacity, increased susceptibility to apoptosis and expression of immune inhibitory receptors (11, 20) that directly impede the host effort to mount an effective immunity against pathogens (21, 22).”
BackgroundMechanism and potential predictive biomarkers of immune checkpoint inhibitors in NSCLC
Qu, J., Jiang, M., Wang, L., Zhao, D., Qin, K., Wang, Y., Tao, J., & Zhang, X. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.109996 · Cited by 46
The metabolic hormone leptin promotes the function of TFH cells and supports vaccine responses
Deng, J., Chen, Q., Chen, Z., Liang, K., Gao, X., Wang, X., Makota, F. V., Ong, H. S., Wan, Y., Luo, K., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23220-x · Cited by 47
Acute Kidney Injury is Aggravated in Aged Mice by the Exacerbation of Proinflammatory Processes
Márquez‐Expósito, L., Tejedor-Santamaria, L., Santos‐Sanchez, L., Valentijn, F. A., Cantero‐Navarro, E., Rayego‐Mateos, S., Rodrigues-Díez, R. R., Tejera‐Muñoz, A., Marchant, V. A., Sanz, A. B., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.662020 · Cited by 46
“Many evidences in humans indicate that the elderly exhibit low-grade systemic chronic inflammation even in healthy conditions (Goronzy and Weyand, 2013; Franceschi and Campisi, 2014).”
BackgroundT-Cell Senescence in Human Metabolic Diseases
Nga, H. T., Nguyen, T. L., & Yi, H. (2024) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2024.0140 · Cited by 47
From Infections to Anthropogenic Inflicted Pathologies: Involvement of Immune Balance
Lee, F., & Lawrence, D. A. (2017) · Journal of Toxicology and Environmental Health Part B · doi:10.1080/10937404.2017.1412212 · Cited by 45
van de Sandt, C. E., Nguyen, T. H. O., Gherardin, N. A., Crawford, J. C., Samir, J., Minervina, A. A., Pogorelyy, M. V., Rizzetto, S., Szeto, C. W., Kaur, J., et al. (2023) · Nature Immunology · doi:10.1038/s41590-023-01633-8 · Cited by 47
“These changes are defined as immunosenescence 24,25 .”
BackgroundKunze, U. (2015) · Ticks and Tick-borne Diseases · doi:10.1016/j.ttbdis.2015.12.018 · Cited by 44
Impact of stress on aged immune system compartments: Overview from fundamental to clinical data
Fali, T., Vallet, H., & Sauce, D. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2018.02.007 · Cited by 46
“It's outlined by several characteristics that affect the adaptive and innate immune compartment (Goronzy & Weyand, 2013), as well as the hematopoietic compartment.”
BackgroundUpdates on Merkel Cell Carcinoma
Emge, D. A., & Cardones, A. R. (2019) · Dermatologic Clinics · doi:10.1016/j.det.2019.06.002 · Cited by 45
Human Toll-Like Receptor 8-Selective Agonistic Activities in 1-Alkyl-1 H -benzimidazol-2-amines
Beesu, M., Malladi, S. S., Fox, L. M., Jones, C. D., Dixit, A., & David, S. A. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm500701q · Cited by 43
Bowirrat, A. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12111817 · Cited by 46
Immunologic Changes in Frail Older Adults
Wang, G. C., & Casolaro, V. (2014) · Europe PMC (PubMed Central) · doi:10.14273/unisa-236 · Cited by 44
“Remarkably, while at least 10 5 -10 6 clones account for the functional diversity of the T-cell receptor (TCR) repertoire in the healthy adult memory T-cell population, these can be reduced by up to 2 orders of magnitude in the senescent immune system [17,22].”
BackgroundImmunometabolism at the cornerstone of inflammaging, immunosenescence, and autoimmunity in COVID-19
Omarjee, L., Perrot, F., Meilhac, O., Mahé, G., Bousquet, G., & Janin, A. (2020) · Aging · doi:10.18632/aging.202422 · Cited by 43
“Immunosenescence is characterized by decreased naïve T-cells, increased memory T-cells, and poor response to newly-encountered antigens and vaccines [34, 35].”
BackgroundThe influence of immunological stressors on traumatic brain injury
Sun, M., McDonald, S. J., Brady, R. D., O'Brien, T. J., & Shultz, S. R. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.01.007 · Cited by 41
“Immunosenescence includes two components: diminished immunological competence in response to antigens (Goronzy and Weyand, 2013; Shaw et al., 2013); and elevated basal inflammation that can involve up-regulation of pro-inflammatory cytokines, clotting factors, and acute phase reactants (Shaw et…”
Cytomegalovirus Exposure in the Elderly Does Not Reduce CD8 T Cell Repertoire Diversity
Lindau, P., Mukherjee, R., Gutschow, M. V., Vignali, M., Warren, E. H., Riddell, S. R., Makar, K. W., Turtle, C. J., & Robins, H. S. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1800217 · Cited by 42
Li, N., Ye, Y., Wu, Y., Li, L., Hu, J., Luo, D., Li, Y., Yang, J., Gao, Y., Hai, W., et al. (2023) · iScience · doi:10.1016/j.isci.2023.106571 · Cited by 44
Immunosenescence and aging in HIV
Tsoukas, C. M. (2014) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0000000000000077 · Cited by 40
van Opstal, E. J., Kolling, G. L., Moore, J. H., Coquery, C. M., Wade, N. S., Loo, W. M., Bolick, D. T., Shin, J. H., Erickson, L. D., & Warren, C. A. (2016) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiw071 · Cited by 39
“pneumoniae, and influenza.[10] Antibody responses specific for C.”
BackgroundReduced insulin/IGF1 signaling prevents immune aging via ZIP-10/bZIP–mediated feedforward loop
Lee, Y., Jung, Y., Jeong, D., Hwang, W., Ham, S., Park, H. H., Kwon, S., Ashraf, J. M., Murphy, C. T., & Lee, S. (2021) · The Journal of Cell Biology · doi:10.1083/jcb.202006174 · Cited by 40
Age as a risk factor in vasculitis
Gloor, A. D., Berry, G. J., Goronzy, J. J., & Weyand, C. M. (2022) · Seminars in Immunopathology · doi:10.1007/s00281-022-00911-1 · Cited by 44
“It is now understood that the immune aging process begins in the 3rd decade of life and accelerates after the age of 50 years [18-20].”
Self-citationCapelle, C., Ciré, S., Hedin, F., Hansen, M., Pavelka, L., Grzyb, K., Kyriakis, D., Hunewald, O. E., Konstantinou, M., Revets, D., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-43053-0 · Cited by 46
“The age range has a major impact on immunological parameters 101,102 .”
BackgroundFlagellin‐dependent TLR 5/caveolin‐1 as a promising immune activator in immunosenescence
Lim, J. S., Nguyen, K. C. T., Nguyen, C. T., Jang, I., Han, J. M., Fabian, C., Lee, S. E., Rhee, J. H., & Cho, K. A. (2015) · Aging Cell · doi:10.1111/acel.12383 · Cited by 39
“Elderly individuals exhibit a decreased ability to resist infectious diseases and generate robust, protective immune responses against vaccinepreventable diseases, including influenza and pneumonia (Boraschi et al., 2010; Goronzy & Weyand, 2013).”
BackgroundOnyema, O. O., Decoster, L., Njemini, R., Forti, L. N., Bautmans, I., Waele, M. D., & Mets, T. F. (2015) · BMC Cancer · doi:10.1186/s12885-015-2013-3 · Cited by 38
“Immunosenescence has been shown to increase with chronological age among normal adults, even without any disease interference [3, 50, 60].”
BackgroundTelomerase deficiency reflects age-associated changes in CD4+ T cells
Matthe, D. M., Thoma, O., Sperka, T., Neurath, M. F., & Waldner, M. J. (2022) · Immunity & Ageing · doi:10.1186/s12979-022-00273-0 · Cited by 41
“Furthermore, a typical ageassociated feature found in both CD4+ and CD8+ T cells is the loss of the costimulatory molecule CD28 [3, 6].”
InfluentialThe Emerging Role of Senotherapy in Cancer: A Comprehensive Review
Malayaperumal, S., Marotta, F., Kumar, M. M., Somasundaram, I., Ayala, A., Pinto, M. F. M., Banerjee, A., & Pathak, S. (2023) · Clinics and Practice · doi:10.3390/clinpract13040076 · Cited by 41
“With age, the proportions of memory-phenotype T cells in the peripheral T cell population steadily rise, but it is still unclear how this change relates to immunosenescent phenotypes [69,70].”
BackgroundSex Hormone Receptor Expression in the Immune System
Buskiewicz, I. A., Huber, S. A., & Fairweather, D. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802388-4.00004-5 · Cited by 38
Stervbo, U., Bozzetti, C., Baron, U., Jürchott, K., Meier, S., Mälzer, J. N., Nienen, M., Olek, S., Rachwalik, D., Schulz, A. R., et al. (2015) · AGE · doi:10.1007/s11357-015-9829-2 · Cited by 37
“Indeed, memory T cells expand in the elderly, and the memory compartment is altered to contain larger pools of fewer clones (reviewed in Goronzy and Weyand 2013).”
BackgroundShifrut, E., Baruch, K., Gal, H., Ndifon, W. O., Deczkowska, A., Schwartz, M., & Friedman, N. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00379 · Cited by 37
“In addition, susceptibility to infectious diseases inclines with age (32) due to a combination of several factors such as immune senescence (33), transcriptional changes (34), and loss of de novo production of naïve T cells (35).”
BackgroundNascimento, C. M. C., Zazzetta, M. S., Gomes, G. A. O., Orlandi, F. D. S., Gramani‐Say, K., Vasilceac, F. A., Gratão, A. C. M., Pavarini, S. C. I., & Cominetti, M. R. (2018) · BMC Geriatrics · doi:10.1186/s12877-018-0961-6 · Cited by 37
Aging-associated patterns in the expression of human endogenous retroviruses
Nevalainen, T., Autio, A., Mishra, B. H., Marttila, S., Jylhä, M. K., & Hurme, M. (2018) · PLoS ONE · doi:10.1371/journal.pone.0207407 · Cited by 37
Haralambieva, I. H., Ovsyannikova, I. G., Kennedy, R. B., Zimmermann, M. T., Grill, D. E., Oberg, A. L., & Poland, G. A. (2016) · Vaccine · doi:10.1016/j.vaccine.2016.06.034 · Cited by 36
“Immunosenescence is a profound age-related dysregulation of the immune system, which leads to impaired immunity/protection following immunization, or significant morbidity and mortality from infection as a result of age-associated changes in both innate and adaptive immune system components [6, 7].”
BackgroundAgeing and ocular surface immunity
Mashaghi, A., Hong, J., Chauhan, S. K., & Dana, R. (2016) · British Journal of Ophthalmology · doi:10.1136/bjophthalmol-2015-307848 · Cited by 36
Friend or foe: the dichotomous impact of T cells on neuro-de/re-generation during aging
Coder, B., Wang, W., Wang, L., Wu, Z., Zhuge, Q., & Su, D. (2016) · Oncotarget · doi:10.18632/oncotarget.12572 · Cited by 36
“One aspect that has been overlooked is that vaccination of immunosenescent patients is not efficient and all elderly patients exhibit some degree of immunosenescence [39].”
BackgroundImmune modulatory capacity of probiotic lactic acid bacteria and applications in vaccine development
Mojgani, N., Shahali, Y., & Dadar, M. (2020) · Beneficial Microbes · doi:10.3920/bm2019.0121 · Cited by 35
Hyperprogressive Disease in Cancers Treated With Immune Checkpoint Inhibitors
Shen, P., Han, L., Ba, X., Qin, K., & Tu, S. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.678409 · Cited by 36
“In addition, T cell signaling through T cell receptors has been found to decrease with age (Solana et al., 2012; Goronzy and Weyand, 2013).”
BackgroundImmunosenescence and cancer: Opportunities and challenges
Fu, Z., Xu, H., Yue, L., Zheng, W., Pan, L., Gao, F., & Liu, X. (2023) · Medicine · doi:10.1097/md.0000000000036045 · Cited by 37
“[9,15,16] The thymus consists of 2 distinct tissue types: epithelial tissue, which has thymic developmental functions, and non-epithelial space surrounding blood vessels that lacks thymic developmental functions.”
BackgroundHodel, K. V. S., Fiuza, B. S. D., Conceição, R. S., Aleluia, A. C. M., Pitanga, T. N., Fonseca, L. M. D. S., Valente, C. O., Rezende, C. S. M. E., & Machado, B. A. S. (2024) · Pharmaceuticals · doi:10.3390/ph17060807 · Cited by 38
“This decline in immune function necessitates special attention in vaccine development and administration to protect against age-related diseases [147].”
BackgroundBhattacharya, P., Dey, R., Dagur, P. K., Joshi, A. B., Ismail, N., Gannavaram, S., Debrabant, A., Akue, A. D., KuKuruga, M. A., Selvapandiyan, A., et al. (2016) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0004963 · Cited by 34
“Immune dysfunction is a hallmark of aging leading to an increased susceptibility to infectious diseases in older individuals [16, 60].”
BackgroundCompartmentalized effects of aging on group 2 innate lymphoid cell development and function
D’Souza, S. S., Shen, X., Fung, I. T. H., Ye, L., Kuentzel, M. L., Chittur, S. V., Furuya, Y., Siebel, C. W., Maillard, I. P., Metzger, D. W., et al. (2019) · Aging Cell · doi:10.1111/acel.13019 · Cited by 36
“However, although adaptive T/B lymphopoiesis is dimin‐ ished with aging (Chinn et al., 2012; Goronzy & Weyand, 2013; Nikolich‐Zugich, 2018), early ILC2 development in the BM is instead drastically increased in old mice due to enhanced Notch signaling.”
BackgroundXu, W., Lau, Z. W. X., Fülöp, T., & Larbi, A. (2020) · Cells · doi:10.3390/cells9051181 · Cited by 36
“These increased incidences of diseases observed in elderly individuals could be attributed to the immune system being dysfunctional with age and this is often termed as immunosenescence [22].”
BackgroundTreanor, J. J., Sherwood, J., Cramer, J. P., Cam, N. L., Lin, S., Baehner, F., & Borkowski, A. (2020) · Vaccine · doi:10.1016/j.vaccine.2020.06.011 · Cited by 35
Aiello, A., Ligotti, M. E., Garnica, M., Accardi, G., Calabrò, A., Pojero, F., Arasanz, H., Bocanegra, A., Blanco, E., Chocarro, L., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179880 · Cited by 37
“an effective approach to improve the health of this age category is preventive medicine and vaccination [3,4].”
BackgroundThe Biology of Aging and Lymphoma: a Complex Interplay
Sarkozy, C., Salles, G. A., & Falandry, C. (2015) · Current Oncology Reports · doi:10.1007/s11912-015-0457-x · Cited by 36
Impaired Efferocytosis Enables Apoptotic Osteoblasts to Escape Osteoimmune Surveillance During Aging
Xu, R., Xie, H., Shen, X., Huang, J., Zhang, H., Fu, Y., Zhang, P., Guo, S., Wang, D., Li, S., et al. (2023) · Advanced Science · doi:10.1002/advs.202303946 · Cited by 33
Accelerated immune ageing is associated with COVID-19 disease severity
Lord, J. M., Veenith, T., Sullivan, J., Sharma‐Oates, A., Richter, A. G., Greening, N. J., McAuley, H., Evans, R. A., Moss, P. A. H., Moore, S. C., et al. (2024) · Immunity & Ageing · doi:10.1186/s12979-023-00406-z · Cited by 35
“…of immunesenescence include an increased risk of bacterial infections, reactivation of latent viruses, poor vaccine responses, increased risk of chronic inflammatory conditions [61, 62] and organ functional decline [63], severe COVID-19 survivors can thus be considered as a vulnerable population.”
BackgroundStervbo, U., Nienen, M., Weist, B. J. D., Kuchenbecker, L., Hecht, J., Wehler, P., Westhoff, T. H., Reinke, P., & Babel, N. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00767 · Cited by 34
“Such permanent antigenic stimuli can lead to clonal skewing with an expansion of a few clones, similar to a phenomenon described for older patients with CMV reactivations (46).”
ResultMachine Learning Approaches to TCR Repertoire Analysis
Katayama, Y., Yokota, R., Akiyama, T., & Kobayashi, T. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.858057 · Cited by 35
“Also, each disease may affect repertoire uniquely [e.g., the difference between CMV and varicella zoster virus (VZV) (178)].”
BackgroundHuibers, M. M. H., Vink, A., Kaldeway, J., Huisman, A., Timmermans, K., Leenders, M. B., Schipper, M. E. I., Lahpor, J. R., Kirkels, H., Klöpping, C., et al. (2014) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2014.07.016 · Cited by 34
“A possible explanation for this observation could be the fact that aging is frequently associated with a decline in immune function [31,32].”
BackgroundKhaledi, M., Poureslamfar, B., Alsaab, H. O., Tafaghodi, S., Hjazi, A. M., Singh, R., Alawadi, A. H., Alsaalamy, A. H., Qasim, Q. A., & Sameni, F. (2024) · Annals of Microbiology · doi:10.1186/s13213-023-01744-5 · Cited by 50
“Age-related immune system disruption can result from a number of factors, such as persistent viral infection and the production of damage-associated molecular patterns (DAMPs) (Gibson et al. 2016; Goronzy and Weyand 2013; Goronzy et al. 2001).”
BackgroundTree Longevity: Multifaceted Genetic Strategies and Beyond
Liu, S., Xu, H., Wang, G., Jin, B., Cao, F., & Wang, L. (2024) · Plant Cell & Environment · doi:10.1111/pce.15146 · Cited by 36
Immunotherapy and senolytics in head and neck squamous cell carcinoma: phase 2 trial results
Liu, N., Wu, J., Deng, E., Zhong, J., Wei, B., Cai, T., Xie, Z., Duan, X., Fu, S., Osei-Hwedieh, D. O., et al. (2025) · Nature Medicine · doi:10.1038/s41591-025-03873-7 · Cited by 41
Efficacy and Safety of an mRNA Seasonal Influenza Vaccine in Adults
Leroux-Roels, I., Huang, G., Ferguson, M., Kohli, A., Clark, R., Bickel, M., Soens, M., Du, E., Pucci, A., Hicks, B., et al. (2026) · New England Journal of Medicine · doi:10.1056/nejmoa2516491 · Cited by 37
Muggen, A. F., de Jong, M. M. E., Wolvers-Tettero, I. L. M., Kallemeijn, M. J., Teodósio, C., Darzentas, N., Stadhouders, R., IJspeert, H., van der Burg, M., van IJcken, W. F. J., et al. (2019) · Immunity & Ageing · doi:10.1186/s12979-019-0163-x · Cited by 32
Hasegawa, T., Feng, Z., Yan, Z., Ngo, K. H., Hosoi, J., & Demehri, S. (2019) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2019.11.017 · Cited by 33
Genetic and phenotypic analysis of the causal relationship between aging and COVID-19
Ying, K., Zhai, R., Pyrkov, T. V., Shindyapina, A. V., Mariotti, M., Fedichev, P. O., Shen, X., & Gladyshev, V. N. (2021) · Communications Medicine · doi:10.1038/s43856-021-00033-z · Cited by 37
Vaccination in the Elderly: What Can Be Recommended?
Lang, P. O., & Aspinall, R. (2014) · Drugs & Aging · doi:10.1007/s40266-014-0193-1 · Cited by 33
“In addition, several studies have been undertaken on possible reasons for this problem and have produced a large number of studies on age-associated changes in the immune system [17, 18, 21, 110–112].”
BackgroundPavlicek, D., Krebs, J., Capossela, S., Bertolo, A., Engelhardt, B., Pannek, J., & Stoyanov, J. V. (2017) · Immunity & Ageing · doi:10.1186/s12979-017-0103-6 · Cited by 31
“manifests as a decline in immune function, a higher susceptibility to infectious diseases and a reduced response to vaccines [9, 10].”
Eremenko, E., Mittal, K., Berner, O., Kamenetsky, N., Nemirovsky, A., Elyahu, Y., & Monsonego, A. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.04.019 · Cited by 33
Factors influencing the immunogenicity of influenza vaccines
Wen, S., Wu, Z., Zhong, S., Mao, L., & Shu, Y. (2021) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2021.1875761 · Cited by 34
“The effects of immunosenescence have also been demonstrated by numerous studies in mouse model.(89,90) In a word, it is of great significance for the public health to popularize the coverage of influenza vaccination among the elderly and provide them with a more optimized vaccination”
BackgroundRisk Factors for Long COVID in Older Adults
Hu, Y., Liu, Y., Zheng, H., & Liu, L. (2023) · Biomedicines · doi:10.3390/biomedicines11113002 · Cited by 32
“This state, known as immunosenescence, is characterized by chronic low-grade inflammation and a decline in the ability to respond to and defend against external threats [37,38].”
BackgroundZidar, D. A., Mudd, J. C., Juchnowski, S. M., Lopes, J. P., Sparks, S. D., Park, S. S., Ishikawa, M., Osborne, R. J., Washam, J. B., Chan, C. C. W., et al. (2015) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.115.306112 · Cited by 30
Kalim, H., Wahono, C. S., Permana, B. P. O., Pratama, M. Z., & Handono, K. (2021) · Reumatologia/Rheumatology · doi:10.5114/reum.2021.110318 · Cited by 30
“Another study also showed that IFN-γ levels produced by CD4+CD57+ T cells were markedly lower than CD8+CD57+ T cells [21].”
ResultWagoner, Z. W., Yates, T. B., Hernandez‐Davies, J. E., Sureshchandra, S., Joloya, E. M., Jain, A., de Assis, R., Kastenschmidt, J. M., Sorn, A. M., Mitul, M. T., et al. (2025) · Cell stem cell · doi:10.1016/j.stem.2025.01.014 · Cited by 30
Premature aging of circulating T cells predicts all-cause mortality in hemodialysis patients
Xiang, F., Chen, R., Cao, X., Shen, B., Chen, X., Ding, X., & Zou, J. (2020) · BMC Nephrology · doi:10.1186/s12882-020-01920-8 · Cited by 30
Immunotherapy in older patients with hepatocellular carcinoma
Lyu, N., Yi, J., & Zhao, M. D. (2021) · European Journal of Cancer · doi:10.1016/j.ejca.2021.11.024 · Cited by 29
An adjuvanted zoster vaccine elicits potent cellular immune responses in mice without QS21
Nam, H. J., Hong, S. J., Lee, A., Kim, J., Lee, S.-H., Casper, C., Carter, D., Reed, S. G., Simeon, G., & Shin, E. (2022) · npj Vaccines · doi:10.1038/s41541-022-00467-z · Cited by 29
Sharma, R., Diwan, B., Sharma, A., & Witkowski, J. M. (2022) · Biogerontology · doi:10.1007/s10522-022-09995-6 · Cited by 30
“…changes in the innate and adaptive immune system, even during immunosenescence, have been identified which warrant a cautious approach in using and interpreting studies, especially related to immune modulatory preclinical work, for human translation (Goronzy and Weyand 2013; High et al.”
BackgroundCramer, J. P., Dubischar, K. L., Eder, S., Burchard, G. D., Jelı́nek, T., Jilma, B., Kollaritsch, H., Reisinger, E. C., & Westritschnig, K. (2016) · Vaccine · doi:10.1016/j.vaccine.2016.07.029 · Cited by 28
“In the age group P65 years, concomitant diseases and medications may affect the immune response in addition to the general reduced function of adaptive and innate immune systems, generally referred to as ‘im munosenescence’ [11].”
BackgroundBorgey, F., Henry, L., Lebeltel, J., Lescure, P., Coutour, X. L., Vabret, A., Verdon, R., & Thibon, P. (2019) · Vaccine · doi:10.1016/j.vaccine.2019.01.066 · Cited by 28
Fcγ receptors on aging neutrophils
Gasparoto, T. H., Dalboni, T. M., Amôr, N. G., Abe, A. E., Perri, G., Lara, V. S., Vieira, N. A., Gasparoto, C. T., & Campanelli, A. P. (2021) · Journal of Applied Oral Science · doi:10.1590/1678-7757-2020-0770 · Cited by 28
Mathot, E., Liberman, K., Dinh, H. C., Njemini, R., & Bautmans, I. (2021) · Experimental Gerontology · doi:10.1016/j.exger.2021.111318 · Cited by 29
Chronovaccination: Harnessing circadian rhythms to optimize immunisation strategies
Otasowie, C., Tanner, R., Ray, D. W., Austyn, J. M., & Coventry, B. J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.977525 · Cited by 27
“Frontiers in Immunology 05 progressively reduced responses to Covid vaccinations (75).”
BackgroundA Mathematical Model of Immune Activation with a Unified Self-Nonself Concept
Khailaie, S., Bahrami, F., Janahmadi, M., Milanez‐Almeida, P., Huehn, J., & Meyer‐Hermann, M. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00474 · Cited by 27
“Aging of the immune system, the so-called immunosenescence, is characterized by involution of thymus, decreased number of thymic output, contraction in T cell diversity, and disturbed T cell homeostasis which all result in attenuated immune function and susceptibility to infectious diseases and cancer in the elderly (…”
BackgroundLingblom, C., Kowli, S., Swaminathan, N., Maecker, H. T., & Lambert, S. L. (2018) · Journal of Translational Medicine · doi:10.1186/s12967-018-1528-1 · Cited by 28
“Waning adaptive immunity can be seen in adults as young as 50 years old [1].”
BackgroundImproving intestinal inflammaging to delay aging? A new perspective
Zhang, L., Yan, J., Zhang, C., Feng, S., Zhan, Z., Bao, Y., Zhan, Z., & Chao, G. (2023) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2023.111841 · Cited by 27
Akagi, T., Nagata, N., Miyazaki, H., Harada, T., Takeda, S., Yoshida, Y., Wada, K., Fujita, M., & Watanabe, K. (2019) · BMC Geriatrics · doi:10.1186/s12877-018-1008-8 · Cited by 27
Mucosal TLR5 activation controls healthspan and longevity
Lim, J. S., Jeon, E. J., Go, H. S., Kim, H., Kim, K. Y., Nguyen, T. Q. T., Lee, D. Y., Kim, K. S., Pietrocola, F., Hong, S. H., et al. (2024) · Nature Communications · doi:10.1038/s41467-023-44263-2 · Cited by 32
Age gene expression and coexpression progressive signatures in peripheral blood leukocytes
Irizar, H., Goñi, J., Alzualde, A., Castillo‐Triviño, T., Olascoaga, J., de Munaín, A. L., & Otaegui, D. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.09.003 · Cited by 26
“This deregulation has been defined as immunosenescence (Goronzy & Weyand 2013).”
BackgroundRedefining priorities towards graded travel-related infectious disease research
Torresi, J., & Steffen, R. J. (2017) · Journal of Travel Medicine · doi:10.1093/jtm/tax064 · Cited by 26
Metadata
- Authors
- Goronzy, J. J., & Weyand, C. M.
- Affiliations
- Stanford Medicine (US)
- VA Palo Alto Health Care System (US)
- Corresponding author
- Goronzy, Jörg J
- Venue
- Nature Immunology
- Published
- 2013-04-18
- Volume
- 14
- Issue
- 5
- Pages
- 428-436
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC4183346
- OpenAlex
- W1992431343
- Cited by
- 827
- References
- 115
- Citations by year
- 2026: 66 · 2025: 62 · 2024: 89 · 2023: 76 · 2022: 61 · 2021: 83 · 2020: 58 · 2019: 68 · 2018: 46 · 2017: 59 · 2016: 53 · 2015: 53 · 2014: 38 · 2013: 15
- FWCI
- 4.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P01HL058000, R01HL117913)
- National Eye Institute (R01EY011916)
- National Institute of Allergy and Infectious Diseases (R01AI044142, U01AI089859, R01AI44142, R01AI108906, U19AI090019, R01AI108891, U19AI057266)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR042527)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- immunosenescence, immunological aging, older adults, vaccine response, innate immune dysregulation, mouse models of aging
- MeSH terms
- Aged, Aged, 80 and over, Aging, Animals, Communicable Disease Control, Humans, Immunocompetence, Vaccination, Vaccines, Cellular Senescence, Mice, Adaptive Immunity
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
