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The immune system and aging: a review
Abstract
Abstract The concept of immunosenescence reflects age-related changes in immune responses, both cellular and serological, affecting the process of generating specific responses to foreign and self-antigens. The decline of the immune system with age is reflected in the increased susceptibility to infectious diseases, poorer response to vaccination, increased prevalence of cancer, autoimmune and other chronic diseases. Both innate and adaptive immune responses are affected by the aging process; however, the adaptive response seems to be more affected by the age-related changes in the immune system. Additionally, aged individuals tend to present a chronic low-grade inflammatory state that has been implicated in the pathogenesis of many age-related diseases (atherosclerosis, Alzheimer's disease, osteoporosis and diabetes). However, some individuals arrive to advanced ages without any major health problems, referred to as healthy aging. The immune system dysfunction seems to be somehow mitigated in this population, probably due to genetic and environmental factors yet to be described. In this review, an attempt is made to summarize the current knowledge on how the immune system is affected by the aging process.
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“As humans age, the immune system evolves from the immature and developing immune responses in infants and children, through to immune function that is potentially optimal in adolescents and young adults, followed by a gradual decline in immunity (particularly adaptive processes) in older people [1].”
From Immune function and micronutrient requirements change over the life course (2018) · cites this paper as [1]
In the citing paper
“Some older people age without any major health problems, known as healthy ageing, and immune system dysfunction appears to be mitigated in this population [1].”
From Immune function and micronutrient requirements change over the life course (2018) · cites this paper as [1]
In the citing paper
“Increased levels of circulating pro-inflammatory cytokines (e.g., tumor-necrosis factor alpha, IL-1, and IL-6 [1,25]) characterize low-grade chronic inflammation in older people, a process known as inflamm-aging [1].”
From Immune function and micronutrient requirements change over the life course (2018) · cites this paper as [1]
In the citing paper
“In older people, functional activity of immune cells such as phagocytes and the intracellular respiratory burst necessary to kill pathogens are reduced [1].”
From Immune function and micronutrient requirements change over the life course (2018) · cites this paper as [1]
In the citing paper
“Many of the most common chronic diseases associated with ageing, such as atherosclerosis, Alzheimer’s disease, osteoporosis and diabetes [1], are related to low-grade inflammation [32].”
From Immune function and micronutrient requirements change over the life course (2018) · cites this paper as [1]
In the citing paper
“This is the case in many older people, and these factors may explain why they have a poorer response to vaccines than the young [1,36].”
From Immune function and micronutrient requirements change over the life course (2018) · cites this paper as [1]
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“…apoptotic resistant memory B cells with reduced clonal expansion that leads to impaired antibody functioning and decreased opsonizing capabilities (7, 47, 48), the direction of association in this study was consistent with a previous study that showed that memory B cells were positively…”
Anti-aging based on stem cell therapy: A scoping review
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“Immune activation and response are impaired with increasing age leading to increased susceptibility to infections and malignancies.(9,10)”
BackgroundNanoparticle-based non-viral CRISPR delivery for enhanced immunotherapy
Shin, H., & Kim, J. (2022) · Chemical Communications · doi:10.1039/d1cc05999h · Cited by 14
The CD4/CD8 ratio is associated with coronary artery disease (CAD) in elderly Chinese patients
Gao, P., Rong, H., Lu, T., Tang, G., Si, L., Lederer, J. A., & Xiong, W. (2016) · International Immunopharmacology · doi:10.1016/j.intimp.2016.11.007 · Cited by 15
“Aging is now a well-recognized risk factor for cardiovascular disease, and aging is also characterized by a deficiency of immune function [11].”
BackgroundAge-related gene expression and DNA methylation changes in rhesus macaque
Zhou, M., Zhang, L., Yang, Q. L., Yan, C., Jiang, P., Lan, Y., Wang, J., Tang, R., He, M., Lei, G.-L., et al. (2020) · Genomics · doi:10.1016/j.ygeno.2020.09.021 · Cited by 15
You, Q., Fang, T., Yin, X., Wang, Y., Yang, Y., Zhang, L., & Xue, Y. (2021) · Journal of Immunology Research · doi:10.1155/2021/6539702 · Cited by 15
“The immune system dysfunction seems to be somehow mitigated in this population [38].”
BackgroundCarriers of the p.P522R variant in PLCγ2 have a slightly more responsive immune system
Diks, A. M., Teodosio, C., de Mooij, B., Groenland, R. J., Naber, B. A. E., de Laat, I. F., Vloemans, S. A., Rohde, S., de Jonge, M. I., Lorenz, L., et al. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00604-9 · Cited by 14
“Additionally, B and T-cell receptor (BCR, TCR) diversity decreases upon aging, leaving aged individuals less equipped to deal with neo-antigens [1, 3, 4].”
BackgroundLatent viruses can cause disease by disrupting the competition for the limiting factor p300/CBP
Polansky, H., & Schwab, H. (2018) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-018-0121-1 · Cited by 14
Olagoke, O., Quigley, B. L., Eiden, M., & Timms, P. (2019) · Scientific Reports · doi:10.1038/s41598-019-48880-0 · Cited by 14
Chaos theory for clinical manifestations in multiple sclerosis
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Dysregulated immune cell responses in severe dengue pathogenesis
Yoo, J., Shporn, O. Z., & Sklan, E. H. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1600999 · Cited by 13
“Age is another potential factor in fl uencing immune response variability (172, 173).”
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“This study also found that senescence in CD4 and CD8 T cell compartments was associated with cardiovascular mortality [2, 5, 22].”
Long-Term Immunity and Antibody Response: Challenges for Developing Efficient COVID-19 Vaccines
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“Additionally, new oral leukoplakia in older patients is considered at potentially higher risk than those of the younger individuals, probably due to decreasing immune function and cumulative effect of associated risk factors, unless local factors are identified as risk factors, such as local trauma [18,19].”
BackgroundIs signalment associated with clinicopathological findings in dogs with leishmaniosis?
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Nonlinear changes in pupillary attentional orienting responses across the lifespan
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“Aging is associated with altered regulation of cognitive and bodily function, ranging from memory [51] and attention to autonomic [62] and immune system regulation [12].”
Standardized Multi-Color Flow Cytometry and Computational Biomarker Discovery
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“Shortened leucocyte telomeres, a marker of immunosenescence, may hamper the effectiveness of these cells to replicate and contribute to the diminished resistance to infections often seen in older individuals, particularly if their immune system is already challenged by chronic diseases, systemic inflammation, or other…”
BackgroundLate-onset anti-N-methyl-d-aspartate receptor encephalitis in China
Zhang, L., Liu, X., Jiang, X., Wang, Y., Li, J., & Zhou, D. (2018) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2018.02.025 · Cited by 12
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Clinical Manifestations and Pathophysiology of Sarcopenia
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Li, Y., Qiu, H., Zhao, Z., Qi, F., & Cai, P. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1636483 · Cited by 11
“This knowledge also helps delay immune aging and informs preventative measures to safeguard older populations from age-associated illnesses (67).”
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“However, senescence of the immune system has been linked to autoimmunity (Castelo-Branco and Soveral, 2014).”
BackgroundAnibijuwon, I., Gbala, I., & Adebisi, O. O. (2018) · Notulae Scientia Biologicae · doi:10.15835/nsb10310300 · Cited by 10
“According to the concept of immunosenescence which explains the change in immune responses as a result of aging, individuals belonging to older age groups are more susceptible to infectious diseases, cancer development and auto immune (Castelo-Branco and Soveral, 2013; Simon et al., 2015).”
BackgroundHow latent viruses cause breast cancer: An explanation based on the microcompetition model
Polansky, H., & Schwab, H. (2018) · Bosnian Journal of Basic Medical Sciences · doi:10.17305/bjbms.2018.3950 · Cited by 11
Porphyromonas Gingivalis May Seek the Alzheimer’s Disease Brain to Acquire Iron from Its Surplus
Olsen, I. (2021) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-200272 · Cited by 12
“Of note is also that immunity can be declined in AD due immunosenescence [60].”
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Liver immunology and herbal treatment
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MacConnachie, L. P., Zhang, Y. S., Farina, M. P., Gutiérrez, C., Hoover, A., He, Y., Aiello, A. E., & Noppert, G. A. (2024) · Social Science & Medicine · doi:10.1016/j.socscimed.2024.116698 · Cited by 10
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“…1 (IL-1) and IL-6), chemokines or matrix metalloproteinases, which contribute to the development of a rather pro-inflammatory phenotype, the so-called senescence-associated secretory phenotype (SASP), causing DNA damage and a state of chronic systemic lowgrade inflammation [8, 16, 25–29].”
The role of age-associated B cells in systemic lupus erythematosus
Su, Q. Y., Zheng, X., Han, X.-T., Li, Q., Gao, Y.-R., Zhang, S., & Li, X.-F. (2025) · Journal of Autoimmunity · doi:10.1016/j.jaut.2025.103433 · Cited by 12
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Fu, X., Liu, Q., Sun, X., Chang, H., Liu, Y., & Han, J. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210656 · Cited by 10
“Studies have shown that the immune system dysfunction seems to be mitigated in healthy elderly compared to elderly with age-related diseases [33].”
Metadata
- Authors
- Castelo-Branco, C., & Soveral, I.
- Affiliations
- Faculty of Medicine, Institut Clínic of Gynecology, Obstetrics and Neonatology, University of Barcelona BarcelonaSpain
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- ORCID
- Soveral, Iris
- Venue
- Gynecological Endocrinology
- Publisher
- Informa UK Limited
- Published
- 2013-11-12
- Volume
- 30
- Issue
- 1
- Pages
- 16-22
- ISSN
- 0951-3590 (ISSN-L)
- 1473-0766
- OpenAlex
- W2027663660
- Cited by
- 449
- References
- 97
- Citations by year
- 2026: 16 · 2025: 46 · 2024: 41 · 2023: 50 · 2022: 60 · 2021: 57 · 2020: 36 · 2019: 31 · 2018: 39 · 2017: 26 · 2016: 25 · 2015: 19 · 2014: 3
- FWCI
- 1.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gynecological Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- immunosenescence, aging, immune system, innate immunity, adaptive immunity, low-grade inflammation, vaccine response, cancer susceptibility, autoimmune disease, healthy aging, age-related diseases
- MeSH terms
- Aging, Animals, Endocrine System, Humans, Immune System, Immunity, Innate, Immunologic Deficiency Syndromes, Inflammation, Autoimmunity, Cellular Senescence, Adaptive Immunity
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