Cited by 451T-cell and B-cell ImmunologyGenetics, Aging, and Longevity in Model OrganismsImmune responses and vaccinations

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The immune system and aging: a review

Castelo-Branco, Camil, Soveral, Iris·2014·Gynecological Endocrinology

DOI 10.3109/09513590.2013.852531

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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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Kalyoncuo, S. (2023) · Black Sea Journal of Health Science · doi:10.19127/bshealthscience.1289615 · Cited by 5
Development and validation of a risk-prediction model for immune-related adverse events in patients with non-small-cell lung cancer receiving PD-1/PD-L1 inhibitors
Qiu, Q., Wu, C., Tang, W., Ji, L., Dai, G., Gao, Y., Chen, E., Jiang, H., Xie, X., & Zhang, J. (2023) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b2200631 · Cited by 5
“However, there is a consensus that immune-cell subsets and overall immune function decline with age, and this is called “immune aging” (Castelo-Branco and Soveral, 2014).”
The role of immune aging in Giant Cell Arteritis
Harkins, P., Cowley, S., Harrington, R., Kane, D. J., & Conway, R. P. (2023) · Aging Pathobiology and Therapeutics · doi:10.31491/apt.2023.09.119 · Cited by 5
Elucidation of Immune Regulation Mechanism of Renshen Guben Oral Liquid by Network Pharmacology and Molecular Docking
Tan, Y., Liu, Y., Zhang, J., Li, J., Ye, P.-Z., Stalin, A., Fan, X., Huang, Z., Li, B. J., Wu, C., et al. (2023) · World Journal of Traditional Chinese Medicine · doi:10.4103/2311-8571.391113 · Cited by 6
ANALYTICAL REVIEW OF HEALTHY AGEING IN THE WHO EUROPEAN REGION COUNTRIES AND RUSSIAN FEDERATION
Vorobyev, R. V., & Владимировна, К. А. (2016) · Social Aspects of Population Health · doi:10.21045/2071-5021-2016-51-5-3 · Cited by 6
Sex-Biased Aging Effects on Ig Somatic Hypermutation Targeting
Cui, A., Chawla, D. G., & Kleinstein, S. H. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.2000576 · Cited by 5
A cellular senescence-related genes model allows for prognosis and treatment stratification of hepatocellular carcinoma: A bioinformatics analysis and experimental verification
Li, J., Tan, R., Wu, J., Guo, W., Wang, Y., You, G., Zhang, Y., Yu, Z., Geng, Y., Zan, J., et al. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2022.1099148 · Cited by 5
“Emerging studies report immune dysfunction is significantly associated with HCC development (Mizukoshi and Kaneko, 2019), and cellular senescence acts essential roles in immune dysfunction (Castelo-Branco and Soveral, 2014).”
Background
Comprehensive review on sexual dimorphism to improve scalp acupuncture in nervous system disease
Wang, C., Wang, J., Wu, X., Liu, T., Feng, W., Zhou, H., Chen, C., Shi, L., Lin, M., Liu, T., et al. (2023) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14447 · Cited by 5
“41,42 However, pathogen-associated lesions, including delayed clearance, were associated with male-biased infection.”
Background
Immunosenescence and Alzheimer’s Disease
Fülöp, T., Larbi, A., Khalil, A., Plotka, A., Laurent, B., Ramassamy, C., Bosco, N., Hirokawa, K., Frost, E. H., & Witkowski, J. M. (2021) · Healthy ageing and longevity · doi:10.1007/978-3-030-87532-9_9 · Cited by 4
A TALE OF TWO SCIENTIFIC PARADIGMS: CONFLICTING SCIENTIFIC OPINIONS ON WHAT “FOLLOWING THE SCIENCE” MEANS FOR SARS-COV-2 AND THE COVID-19 PANDEMICPreprint
Quinn, G. A., Connolly, R., ÓhAiseadha, C. O., & Hynds, P. D. (2021) · OSF Preprints (OSF Preprints) · doi:10.31219/osf.io/s9z2p · Cited by 5
Foodborne Diseases and Vulnerable Groups
Obadina, A. O. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-822521-9.00002-2 · Cited by 5
Negative association of C-reactive protein-albumin-lymphocyte index (CALLY index) with all-cause and cardiovascular mortality in population with CKD: the mediating role of biological age acceleration
Huang, D., Wu, H., Zhou, J., Yin, S., Wang, R., & Quan, Z. (2025) · Renal Failure · doi:10.1080/0886022x.2025.2586892 · Cited by 5
“…and malignancies, consequently heightening the risk of all-cause mortality [25,57]. in this context, immune senescence perpetuates chronic inflammation through the persistent secretion of pro-inflammatory cytokines, creating a detrimental feedback loop that exacerbates biological aging [58–60].”
IL-6 and CD4+/CD8+ are Important Indicators for Predicting Prognosis in Elderly AECOPD Patients: A Retrospective Study
Liu, Q., Wang, Y., Cao, X., Zhang, S., & Xie, J. (2025) · Journal of Inflammation Research · doi:10.2147/jir.s496735 · Cited by 4
Core–Shell ZnO2@Cerium-Based Metal–Organic Framework with Low Turnover, Dual-Catalytic Activity for Biosafe Biofilm Dispersal and Immune Modulation
Wu, R., Ge, T., Yu, T., Shi, Q., Shi, R., Ren, Y., Busscher, H. J., Liu, J., & van der Mei, H. C. (2025) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.5c08974 · Cited by 5
Difference between the biologic and chronologic age as an individualized indicator for the skin care intensity selection: skin topography and immune system state studies, parameter correlations with age difference
Суховей, Ю. Г., Костоломова, Е. Г., Unger, I., Koptyug, A. V., & Kaigorodov, D. (2019) · Biomedical Dermatology · doi:10.1186/s41702-019-0050-2 · Cited by 4
The Effect of Mango Mistletoes (Dendrophthoe pentandra) Leaves Extract on Percentage of CD4+CD28+, CD8+CD28+, and interleukin-2 Levels of Aged Balb/c Mice
Handono, K., Pratama, M. Z., Sermoati, I. A., Yuniati, M. G., Haryati, N. P. S., Norahmawati, E., Endharti, A. T., Irwanto, Y., Solikhin, M. B., & Hidayat, S. (2021) · Open Access Macedonian Journal of Medical Sciences · doi:10.3889/oamjms.2021.6182 · Cited by 5
“In humans, with age, viral infections, exposure to antigens, thymus involution, and accumulation of ROS lead to aging of the immune system or known as immunosenescence [15].”
Background
Sleep Variability and Inflammation in Midlife and Older Women
Leger, K. A., Gloger, E. M., Crofford, L. J., McDade, T. W., & Segerstrom, S. C. (2022) · Psychosomatic Medicine · doi:10.1097/psy.0000000000001130 · Cited by 4
“In addition, older age is accompanied with a decline in immune efficacy, resulting in increased inflammation (24).”
Background
Unravelling the genetic variability of host resilience to endo- and ectoparasites in Nellore commercial herds
Gouveia, G. C., Ribeiro, V. M. P., Fortes, M. R. S., Raidan, F. S. S., Reverter, A., Porto-Neto, L. R., de Moraes, M. M., Gonçalves, D. R., Silva, M. V. G. B. D., & Toral, F. L. B. (2023) · Genetics Selection Evolution · doi:10.1186/s12711-023-00844-9 · Cited by 5
“This result might be partially explained by the effect of age on immune response mechanisms [51–53].”
Background
The impact of leukapheresis on immune-cell number and function in patients with advanced cancer
Gulley, J. L., Marté, J. L., Heery, C. R., Madan, R. A., Steinberg, S. M., Leitman, S. F., Tsang, K. Y., & Schlom, J. (2015) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-015-1738-9 · Cited by 4
“This may be important, as reports have suggested a gradual decrease in immune repertoire over time [8].”
Conceptos inmunológicos básicos aplicados a la vacunología
Cambronero, M. R., Prado-Cohrs, D., & Sanroma, M. L. (2017) · Vacunas · doi:10.1016/j.vacun.2017.10.001 · Cited by 4
Analysis of the levels of inflammatory parameters in persons over the age of 90
Zabielska, P., Wieder-Huszla, S., Karakiewicz, B., Skonieczna‐Żydecka, K., Lubkowska, A., & Jurczak, A. (2021) · Experimental Gerontology · doi:10.1016/j.exger.2021.111278 · Cited by 4
CD4+/CD8+ Ratio and Growth Differentiation Factor 8 Levels in Peripheral Blood of Large Canine Males Are Useful Parameters to Build an Age Prediction Model
Lee, H.-J., Hong, S.-J., Kim, S., Kwon, Y., Choi, B., Choi, K.-M., Sheen, S.-H., Lee, M.-J., Hwang, S., Park, K., et al. (2022) · The World Journal of Men s Health · doi:10.5534/wjmh.210003 · Cited by 4
“Relevant to the current work, immunosenescence is one of the major aging traits occurring in both dog and human [6,15,16].”
Background
Vitamin D and estrogen steroid hormones and their immunogenetic roles in Infectious respiratory (TB and COVID-19) diseases
Borborema, M. E. D. A., de Lucena, T. M. C., & Silva, J. D. A. (2023) · Genetics and Molecular Biology · doi:10.1590/1415-4757-gmb-2022-0158 · Cited by 4
“Elderly/menopause Woman: - Suppression of the immune system (Castelo-Branco and Soveral, 2014); - Increased release of pro-inflammatory cytokines (IL-1, IL-6, TNF) and inhibition of IFN-γ release and B and T cells recruitment.”
Evaluation of Clinico-Radiological and Functional Profile of Patients with Bronchiectasis According to FACED Score
Singh, A. K., Bairwa, M., Mangal, V., Qureshi, M. J., & Agnihotri, S. P. (2022) · The Indian Journal of Chest Diseases and Allied Sciences · doi:10.5005/ijcdas-63-2-75 · Cited by 4
Mikronährstoffe, Immunüberwachung und Immunseneszenz
Stoll, G. (2020) · Deutsche Zeitschrift für Onkologie · doi:10.1055/a-1240-8399 · Cited by 4
The effect of pneumococcal immunization on total and antigen-specific B cells in patients with severe chronic kidney disease
Gaultier, G. N., McCready, W. G., & Ulanova, M. (2019) · BMC Immunology · doi:10.1186/s12865-019-0325-9 · Cited by 4
“activation of T-cell response have been found in CKD patients [34, 35].”
Background
Prevalence and clinical profile of comorbidity among newly diagnosed pulmonary tuberculosis patients: a multi-center observational study in eastern China
Wang, W., Wang, X., Chen, S., Li, J., Cheng, Q., Zhang, Y., Wu, Q., Liu, K., Jiang, X., & Chen, B. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1446835 · Cited by 3
“Studies have shown that older people are more susceptible to infections and other chronic diseases (27), which may be related to a decline in the immune system (28).”
Revealing the Landscape Crosstalk Between Reproductive System and Organs Aging
Wu, J., Wu, P., Wang, S., Guan, Y., & Wang, J. (2025) · The FASEB Journal · doi:10.1096/fj.202403410r · Cited by 3
“The function of the immune system declines with age, one specific manifestation of which is that the activity of dendritic cells, macrophages, and neutrophils changes with age [181, 182].”
Pregnancy lab test dynamics resemble rejuvenation of some organs and aging of others
Moran, R., Pridham, G., Toledano, Y., & Alon, U. (2026) · Nature Communications · doi:10.1038/s41467-026-69340-0 · Cited by 3
“Some of the changes in pregnancy resemble changes in aging, such as a shift in immunitytowardsinnateimmunity 5,6 andreducedredbloodcell(RBC) counts 1,7 .”
Opioids and the Immune System
González‐Espinosa, C., Madera-Salcedo, I. K., Molina-Martínez, L. M., & Martínez-Cuevas, F. L. (2022) · Springer eBooks · doi:10.1007/978-3-031-09936-6_12 · Cited by 3
Hormone replacement therapy and COVID-19 outcomes in solid organ transplant recipients compared with the general population
Vinson, A. J., Anzalone, A. J., Schissel, M. E., Dai, R., French, E., Olex, A. L., Mannon, R. B., Wilcox, A. B., Lee, A. M., Graves, A., et al. (2023) · American Journal of Transplantation · doi:10.1016/j.ajt.2023.04.020 · Cited by 3
“Thus, decreasing endogenous sex hormones over the lifespan (gradually in males and more rapidly in females at menopause) are associated with corresponding changes in the immune response.(5) Sex-based differences in COVID-19 risk may be partially attributed to inflammaging, defined as diminishing adaptive immunity and…”
Background
Poor Physical Health in Caregivers of Children with ADHD or ASD and its Association with Health Risk Behaviours: NHIS 2016–2018
Ku, B., & Ghim, S. (2024) · International Journal of Behavioral Medicine · doi:10.1007/s12529-023-10253-3 · Cited by 3
“As older age is a significant factor for experiencing a health problem [21], the current study limited caregivers’ age to 64 years and 11 months.”
Immunomodulatory Effects of Modified Colostrum, Whey, and Their Combination With Other Natural Products: Effects on Natural Killer Cells
Han, X., Vollmer, D. L., Yan, X., Zhang, Y., Zang, M., Zhang, C., Sherwin, C. M. T., & Enioutina, E. Y. (2024) · Current Therapeutic Research · doi:10.1016/j.curtheres.2024.100750 · Cited by 3
Association of blood trihalomethane concentrations with diabetes mellitus in older adults in the US: a cross-sectional study of NHANES 2013–2018
Chen, T., He, H., Tang, W., Liu, Z., & Zhang, H. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1401131 · Cited by 3
“Older adults usually have a low level of immune system and tend to show chronic low-grade in ﬂ ammation, which is related to the pathogenesis of many age-related diseases (atherosclerosis, Alzheimer ’ s disease, osteoporosis, and diabetes) (26).”
Background
Identification of senescence-related biomarkers for osteoporosis based on microarray analysis, Mendelian randomization, and experimental validation
Zhu, Y., Zhao, J., Li, Z., & Chen, Y. (2025) · Mammalian Genome · doi:10.1007/s00335-025-10116-0 · Cited by 3
Executive function and soluble urokinase-type plasminogen activator receptor (suPAR): a longitudinal study of midlife adults
Shell, A., Vize, C. E., Gianaros, P. J., Rasmussen, L. J. H., & Marsland, A. L. (2025) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.06.030 · Cited by 3
IMMUNOMEDIATOR GENE TRANSCRIPTION PROFILING IN BELUGA WHALE (DELPHINAPTERUS LEUCAS) CLINICAL CASES
Hofstetter, A. R., Bonn, W. G. V., & Sacco, R. E. (2020) · Journal of Zoo and Wildlife Medicine · doi:10.1638/2018-0225 · Cited by 3
“One target of HIF-1a is CXCR4, a chemokine receptor important in immune cell trafficking,(57) vasculogenesis, and angiogenesis.(1,9) Thus, the assay panel covered a broad range of immunomediators.”
Background

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
DOI: 10.3109/09513590.2013.852531
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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The immune system and aging: a review

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