The immune system and aging: A review

Castelo-Branco, Camil; Soveral, Iris

doi:10.3109/09513590.2013.852531

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

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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Immune function changes over the life course, developing in infants and children, potentially optimal in adolescents and young adults, and declining in older people.
“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]
Some older people age without any major health problems (healthy ageing), and immune system dysfunction appears to be mitigated in this population.
“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]
Increased levels of circulating pro-inflammatory cytokines characterize low-grade chronic inflammation in older people, a process known as inflamm-aging.
“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 older people, functional activity of immune cells such as phagocytes and the intracellular respiratory burst necessary to kill pathogens are reduced.
“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]
Many of the most common chronic diseases associated with ageing, such as atherosclerosis, Alzheimer's disease, osteoporosis and diabetes, are related to low-grade inflammation.
“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]

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Molecular Mechanisms Involved in the Aging of the T-cell Immune Response
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Natural killer cell function is altered during the primary response of aged mice to influenza infection
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Diversity of NKR expression in aging T cells and in T cells of the aged: The new frontier into the exploration of protective immunity in the elderly
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Effects of age on antibody affinity maturation
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Thymopoiesis in elderly human is associated with systemic inflammatory status
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T lymphocyte proliferative capability to defined stimuli and costimulatory CD28 pathway is not impaired in healthy centenarians
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Age-related decline in proliferative potential of purified stem cell candidates.
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Nasal ciliary beat frequency is age independent
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(2002) · doi:10.1002/1521-4141(200206)32:6

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Sex differences in immune responses
Klein, S. L., & Flanagan, K. L. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.90 · Cited by 6,370 · see citing works
Inflammation in CNS neurodegenerative diseases
Stephenson, J., Nutma, E., van der Valk, P., & Amor, S. (2018) · Immunology · doi:10.1111/imm.12922 · Cited by 966 · see citing works
Epigenetic clock analysis of diet, exercise, education, and lifestyle factors
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“The age-related changes in immune functioning and inflammation are believed to contribute to increased susceptibility of a wide range of diseases later in life, including diabetes, some cancers, cardiovascular, neurodegenerative, auto-immune, and infectious diseases [63, 64].”
Impact of Obesity and Metabolic Syndrome on Immunity
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“However, this change adversely affects immunity in older individuals (96, 100).”
Background
Immune function and micronutrient requirements change over the life course
Maggini, S., Pierre, A., & Calder, P. C. (2018) · Nutrients · doi:10.3390/nu10101531 · Cited by 710 · see citing works
Sexual-dimorphism in human immune system aging
Márquez, E. J., Chung, C.-H., Marches, R., Rossi, R. J., Nehar-Belaid, D., Eroglu, A., Mellert, D. J., Kuchel, G. A., Banchereau, J., & Ucar, D. (2020) · Nature Communications · doi:10.1038/s41467-020-14396-9 · Cited by 584 · see citing works
“Using novel systems immunology pipelines, we discovered a genomic signature of aging that is shared between sexes including (1) declines in T cell functions, (2) increases in cytotoxic (NK, memory CD8+ T) and monocyte cell functions.”
BackgroundMethodInfluential
Malignant transformation of oral leukoplakia: a systematic review of observational studies
Warnakulasuriya, S., & Ariyawardana, A. (2015) · Journal of Oral Pathology and Medicine · doi:10.1111/jop.12339 · Cited by 505 · see citing works
Immunology of aging: the birth of inflammaging
Fulop, T., Larbi, A., Pawelec, G., Khalil, A., Cohen, A. A., Hirokawa, K., Witkowski, J. M., & Franceschi, C. (2021) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-021-08899-6 · Cited by 464 · see citing works
“Over several decades, the paradigm was and still is that aging is related to the shrinkage of naïve T cells, which explains why certain diseases are increasing such as infection, cancer are increasing and why older subjects are not able to respond to the vaccination as efficiently as young subjects [49, 50].”
Background
Age Correlates with Response to Anti-PD1, Reflecting Age-Related Differences in Intratumoral Effector and Regulatory T-Cell Populations
Kugel, C. H., Douglass, S. M., Webster, M. R., Kaur, A., Liu, Q., Yin, X., Weiss, S. A., Darvishian, F., Al-Rohil, R. N., Ndoye, A., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-1116 · Cited by 367 · see citing works
16S rRNA Next Generation Sequencing Analysis Shows Bacteria in Alzheimer’s Post-Mortem Brain
Emery, D. C., Shoemark, D. K., Batstone, T. E., Waterfall, C. M., Coghill, J. A., Cerajewska, T. L., Davies, M., West, N. X., & Allen, S. J. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00195 · Cited by 317 · see citing works
“Immune response is known to be affected by age, with a waning in function of the adaptive immune system with increasing age (Weksler et al., 2005; Castelo-Branco and Soveral, 2014) whereas the innate immune system remains relatively intact, providing a rapid but short-lived acute defense against…”
Background
Comparison of efficacy of immune checkpoint inhibitors (ICIs) between younger and older patients: A systematic review and meta-analysis
Nishijima, T. F., Muss, H. B., Shachar, S. S., & Moschos, S. J. (2016) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2016.02.006 · Cited by 293 · see citing works
“In addition to numeric defects, functional defects have been described, such deficiency in CD28 co-stimulation, upregulation of co-inhibitory immune checkpoints PD-1 and Tim-3 [15], diminution of intracellular signaling important for T-cell activation, decreased cytokine production and IL-2 signaling [16].”
Background
Streptococcus pneumoniae’s Virulence and Host Immunity: Aging, Diagnostics, and Prevention
Brooks, L. R. K., & Mias, G. I. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01366 · Cited by 286 · see citing works
The Confluence of Sex Hormones and Aging on Immunity
Gubbels Bupp, M. R., Potluri, T., Fink, A. L., & Klein, S. L. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01269 · Cited by 277 · see citing works
“Comp Biochem Physiol A Comp Physiol (1985) 81(4):935–8.”
BackgroundInfluential
Geographic variation in the aetiology, epidemiology and microbiology of bronchiectasis
Chandrasekaran, R., Aogáin, M. M., Chalmers, J. D., Elborn, J. S., & Chotirmall, S. H. (2018) · BMC Pulmonary Medicine · doi:10.1186/s12890-018-0638-0 · Cited by 271 · see citing works
“The immune system, and potentially the microbiome, also undergoes its own change with age, a process incompletely understood, termed ‘immunosenescence’ [13, 14].”
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Aging and cancer: The role of macrophages and neutrophils
Jackaman, C., Tomay, F., Duong, L., Abdol Razak, N. B., Pixley, F. J., Metharom, P., & Nelson, D. J. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.03.008 · Cited by 251 · see citing works
Sex Differences in Immunity to Viral Infections
Jacobsen, H., & Klein, S. L. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.720952 · Cited by 234 · see citing works
Effects of Acute and Chronic Exercise on Immunological Parameters in the Elderly Aged: Can Physical Activity Counteract the Effects of Aging?
Sellami, M., Gasmi, M., Denham, J., Hayes, L. D., Stratton, D., Padulo, J., & Bragazzi, N. L. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02187 · Cited by 224 · see citing works
“Langerhans cells in the skin and monocyte-derived DCs) and the DCs of lymphoid origin (or plasmacytoid DCs) (128).”
BackgroundInfluential
Human longevity: 25 genetic loci associated in 389,166 UK biobank participants
Pilling, L. C., Kuo, C.-L., Sicinski, K., Tamosauskaite, J., Kuchel, G. A., Harries, L. W., Herd, P., Wallace, R., Ferrucci, L., & Melzer, D. (2017) · Aging · doi:10.18632/aging.101334 · Cited by 211 · see citing works
“Several loci are near genes involved in inflammation, an important pathway in the development of biological aging [21].”
Background
A hypothesis for pathobiology and treatment of COVID‐19 : The centrality of ACE1 / ACE2 imbalance
Sriram, K., & Insel, P. A. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15082 · Cited by 195 · see citing works
Association of inflammatory mediators with frailty status in older adults: results from a systematic review and meta-analysis
Marcos-Pérez, D., Sánchez-Flores, M., Proietti, S., Bonassi, S., Costa, S., Teixeira, J. P., Fernandez-Tajes, J. J., Pásaro, E., Laffón, B., & Valdiglesias, V. (2020) · GeroScience · doi:10.1007/s11357-020-00247-4 · Cited by 188 · see citing works
Obesity and COVID-19: what makes obese host so vulnerable?
Mohammad, S., Aziz, R., Mahri, S. A., Malik, S. S., Haji, E. M., Khan, A. H., Khatlani, T., & Bouchama, A. (2021) · Immunity & Ageing · doi:10.1186/s12979-020-00212-x · Cited by 180 · see citing works
“Consequently, obesity is assumed to promote premature “aging” of the immune system [92].”
Background
Inflammatory Markers Change with Age, but do not Fall Beyond Reported Normal Ranges
Wyczałkowska-Tomasik, A., Czarkowska‐Pączek, B., Zielenkiewicz, M., & Pączek, L. (2015) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-015-0357-7 · Cited by 165 · see citing works
“IL-8 is one of the most important chemokines responsible for recruiting circulating neutrophils to a site of infection, e.g., chemotaxis, which is probably not affected by age (Castelo-Branco and Soveral 2014; Franceschi et al. 2000).”
BackgroundInfluential
Sex and Gender Impact Immune Responses to Vaccines Among the Elderly
Fink, A. L., & Klein, S. L. (2015) · Physiology · doi:10.1152/physiol.00035.2015 · Cited by 154 · see citing works
Skeletal muscle regeneration and impact of aging and nutrition
Domingues-Faria, C., Vasson, M.-P., Goncalves-Mendes, N., Boirie, Y., & Walrand, S. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2015.12.004 · Cited by 157 · see citing works
The Oral Microbiome of Denture Wearers Is Influenced by Levels of Natural Dentition
O’Donnell, L. E., Robertson, D. P., Nile, C. J., Cross, L. J., Riggio, M. P., Sherriff, A., Bradshaw, D. J., Lambert, M., Malcolm, J., Buijs, M. J., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0137717 · Cited by 155 · see citing works
Autoimmunity in the Elderly: Insights from Basic Science and Clinics - A Mini-Review
Watad, ‬., Bragazzi, N. L., Adawi, M., Amital, H., Toubi, E., Katz, B.-S. P., & Shoenfeld, Y. (2017) · Gerontology · doi:10.1159/000478012 · Cited by 137 · see citing works
Antioxidant and immune-enhancing effects of probiotic Lactobacillus plantarum 200655 isolated from kimchi
Yang, S.-J., Lee, J., Lim, S.-M., Kim, Y., Lee, N., & Paik, H. (2018) · Food Science and Biotechnology · doi:10.1007/s10068-018-0473-3 · Cited by 133 · see citing works
Sex Hormones and Anticancer Immunity
Özdemir, B. C., & Dotto, G. P. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-0137 · Cited by 132 · see citing works
Inflammation in cancer: therapeutic opportunities from new insights
Xie, Y., Liu, F., Wu, Y., Zhu, Y., Jiang, Y., Wu, Q., Dong, Z., & Liu, K. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02243-8 · Cited by 134 · see citing works
Nutrition, Immunosenescence, and Infectious Disease: An Overview of the Scientific Evidence on Micronutrients and on Modulation of the Gut Microbiota
Calder, P. C., Ortega, E. F., Meydani, S. N., Adkins, Y. C., Stephensen, C. B., Thompson, B., & Zwickey, H. L. (2022) · Advances in Nutrition · doi:10.1093/advances/nmac052 · Cited by 136 · see citing works
The Impact of Immunosenescence on Pulmonary Disease
Murray, M., & Chotirmall, S. H. (2015) · Mediators of Inflammation · doi:10.1155/2015/692546 · Cited by 124 · see citing works
“Both innate and adaptive arms of immune function are affected [16].”
Influential
Intraocular cytokine profile and autoimmune reactions in retinitis pigmentosa, age-related macular degeneration, glaucoma and cataract
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Pathology of mouse models of accelerated aging
Harkema, L., Youssef, S. A., & de Bruin, A. (2016) · Veterinary Pathology · doi:10.1177/0300985815625169 · Cited by 105 · see citing works
“The functional changes associated with aging are most prominent in the adaptive immune system and lead to a decline in T and B cell function and reduced proliferative capacity of the bone marrow hematopoietic stem cells with a shift from lymphoid differentiation toward myeloid differentiation.(29,129) Age-related redu…”
Influential
Age-related sarcopenia and its pathophysiological bases
Ogawa, S., Yakabe, M., & Akishita, M. (2016) · Inflammation and Regeneration · doi:10.1186/s41232-016-0022-5 · Cited by 109 · see citing works
Age and gender leucocytes variances and references values generated using the standardized ONE‐Study protocol
Kverneland, A. H., Streitz, M., Geissler, E., Hutchinson, J., Vogt, K., Boës, D., Niemann, N., Pedersen, A. E., Schlickeiser, S., & Sawitzki, B. (2016) · Cytometry Part A · doi:10.1002/cyto.a.22855 · Cited by 99 · see citing works
“Conflicting results regarding age-dependent subset changes have been reported (28) indicating that immune cell aging is also influenced by factors such as ethnical or environmental variables, requiring methods to standardize and harmonize immune cell profiling (29–32).”
Method
Gut Microbiota Interaction with the Central Nervous System throughout Life
Ojeda, J., Ávila, A., & Vidal, P. M. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10061299 · Cited by 107 · see citing works
The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors
Deshpande, R. P., Sharma, S., & Watabe, K. (2020) · Cancers · doi:10.3390/cancers12102983 · Cited by 101 · see citing works
Polyphenols as promising biologically active substances for preventing SARS-CoV-2: A review with research evidence and underlying mechanisms
Mehany, T., Khalifa, I., Barakat, H., Althwab, S. A., Alharbi, Y., & Sohaimy, S. A. E. (2021) · Food Bioscience · doi:10.1016/j.fbio.2021.100891 · Cited by 99 · see citing works
Health Care Utilization and Health Care Expenditure of Nepali Older Adults
Acharya, S., Ghimire, S., Jeffers, E. M., & Shrestha, N. (2019) · Frontiers in Public Health · doi:10.3389/fpubh.2019.00024 · Cited by 96 · see citing works
“Biologically, aging is characterized by a gradual, lifelong accumulation of molecular and cellular degeneration that subsequently leads to a decrease in physiological functions, a compromised immune function, and an increased vulnerability to diseases (35, 36).”
Background
Age and Sex: Impact on adipose tissue metabolism and inflammation
Varghese, M., Song, J., & Singer, K. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111563 · Cited by 95 · see citing works
Role of lncRNAs in aging and age‐related diseases
He, J., Tu, C., & Liu, Y. (2018) · Aging Medicine · doi:10.1002/agm2.12030 · Cited by 88 · see citing works
“Moreover, aging is considered as a low‐grade chronic inflammation state, termed inflammaging, where SASP plays an important role.(255) SASP‐asso-”
Background
Aging, Cancer and Immunity
Hong, H., Wang, Q., Li, J., Liu, H. B., Meng, X., & Zhang, H. (2019) · Journal of Cancer · doi:10.7150/jca.30723 · Cited by 89 · see citing works
“There were three major theories which may explain immunosenescence, known as autoimmunity, immunodeficiency and immunodysregulation (6).”
Background
Vitamin D as a Shield against Aging
Fantini, C., Corinaldesi, C., Lenzi, A., Migliaccio, S., & Crescioli, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054546 · Cited by 96 · see citing works
Immunosenescence and vaccine failure in the elderly: strategies for improving response
Boraschi, D., & Italiani, P. (2014) · Immunology Letters · doi:10.1016/j.imlet.2014.06.006 · Cited by 86 · see citing works
Age and Periodontal Health—Immunological View
Ebersole, J. L., Dawson, D. R., Emecen‐Huja, P., Pandruvada, S. N. M., Basu, A., Nguyen, L., Zhang, Y., & González, O. A. (2018) · Current Oral Health Reports · doi:10.1007/s40496-018-0202-2 · Cited by 84 · see citing works
Age-related spontaneous lacrimal keratoconjunctivitis is accompanied by dysfunctional T regulatory cells
Coursey, T. G., Bian, F., Zaheer, M., Pflugfelder, S. C., Volpe, E., & de Paiva, C. S. (2016) · Mucosal Immunology · doi:10.1038/mi.2016.83 · Cited by 82 · see citing works
Possible correlation between gut microbiota and immunity among healthy middle-aged and elderly people in southwest China
Shen, X. P., Miao, J., Wan, Q., Wang, S., Li, M., Pu, F., Wang, G., Qian, W. P., Yu, Q., Marotta, F., et al. (2018) · Gut Pathogens · doi:10.1186/s13099-018-0231-3 · Cited by 79 · see citing works
“1090) software was used to identify representative sequences for each operational taxonomic unit (OTU), generated from complete linkage clustering with a 97% similarity against de novo clustered sequences and aligned to the Greengenes database (v201305 [8]).”
BackgroundMethod
COPD as a Disease of Immunosenescence
Cho, W., Lee, C. G., & Kim, L. K. (2019) · Yonsei Medical Journal · doi:10.3349/ymj.2019.60.5.407 · Cited by 79 · see citing works
“Both innate immunity and adaptive immunity are affected by aging.(27) Aging innate immune cells, such as neutrophils, macrophages, dendritic cells, and natural killer cells, undergo functional decline in phagocytosis, chemotaxis, their ability to secrete inflammatory cytokine, antigen-presenting capacity, and bacteric…”
Background
Dietary micronutrients in the wake of COVID-19: an appraisal of evidence with a focus on high-risk groups and preventative healthcare
McAuliffe, S., Ray, S., Fallon, E., Bradfield, J., Eden, T., & Kohlmeier, M. (2020) · BMJ Nutrition Prevention & Health · doi:10.1136/bmjnph-2020-000100 · Cited by 75 · see citing works
Inhibition of interleukin-6 decreases atrogene expression and ameliorates tail suspension-induced skeletal muscle atrophy
Yakabe, M., Ogawa, S., Ota, H., Iijima, K., Eto, M., Ouchi, Y., & Akishita, M. (2018) · PLoS ONE · doi:10.1371/journal.pone.0191318 · Cited by 74 · see citing works
The Contribution of Oxidative Stress and Inflamm-Aging in Human and Equine Asthma
Bullone, M., & Lavoie, J. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18122612 · Cited by 72 · see citing works
“mechanism for the reduced cytotoxicity of the single cell [113].”
BackgroundInfluential
The lethal sex gap: COVID-19
Márquez, E. J., Trowbridge, J. J., Kuchel, G. A., Banchereau, J., & Ucar, D. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-00183-z · Cited by 71 · see citing works
Fat-Soluble Vitamins
Stevens, S. L. (2021) · Nursing Clinics of North America · doi:10.1016/j.cnur.2020.10.003 · Cited by 72 · see citing works
Time-restricted feeding influences immune responses without compromising muscle performance in older men
Gasmi, M., Sellami, M., Denham, J., Padulo, J., Kuvačić, G., Selmi, W., & Khalıfa, R. (2018) · Nutrition · doi:10.1016/j.nut.2017.12.014 · Cited by 68 · see citing works
The influence of the microbiota on immune development, chronic inflammation, and cancer in the context of aging
Tibbs, T., Lopez, L. R., & Arthur, J. C. (2019) · Microbial Cell · doi:10.15698/mic2019.08.685 · Cited by 70 · see citing works
“For cells of the innate immune system, there are reported functional differences for every major cell type [31].”
Background
Systematic exploration of Astragalus membranaceus and Panax ginseng as immune regulators: Insights from the comparative biological and computational analysis
Liu, J., Nile, S. H., Xu, G., Wang, Y., & Kai, G. (2019) · Phytomedicine · doi:10.1016/j.phymed.2019.153077 · Cited by 65 · see citing works
Antibodies in Melioidosis: The Role of the Indirect Hemagglutination Assay in Evaluating Patients and Exposed Populations
Chaichana, P., Jenjaroen, K., Amornchai, P., Chumseng, S., Langla, S., Rongkard, P., Sumonwiriya, M., Jeeyapant, A., Chantratita, N., Teparrukkul, P., et al. (2018) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.17-0998 · Cited by 62 · see citing works
“due to age-related decline of naive B-cell production and impaired memory B cells, leading to a decrease of circulating antibodies(26,43,44) and their functional activities.(45) However, it”
Background
Enhanced inflammation in aged mice following infection withStreptococcus pneumoniaeis associated with decreased IL-10 and augmented chemokine production
Williams, A. E., José, R. J. P., Brown, J., & Chambers, R. C. (2015) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00141.2014 · Cited by 62 · see citing works
Revisiting the Role of Thiopurines in Inflammatory Bowel Disease Through Pharmacogenomics and Use of Novel Methods for Therapeutic Drug Monitoring
Lim, S. Z., & Chua, E. W. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01107 · Cited by 62 · see citing works
“This is due to the dysregulated immune function in elderly patients, leading to their increased susceptibility to infection, malignancies, and other adverse drug reactions (Gavazzi and Krause, 2002; Weng, 2006; CasteloBranco and Soveral, 2013).”
Ingestion, Immunity, and Infection: Nutrition and Viral Respiratory Tract Infections
Govers, C., Calder, P. C., Savelkoul, H. F. J., Albers, R., & van Neerven, R. J. J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.841532 · Cited by 66 · see citing works
Microglial response to aging and neuroinflammation in the development of neurodegenerative diseases
Han, T., Xu, Y., Sun, L., Hashimoto, M., & Wei, J. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.385845 · Cited by 60 · see citing works
“The adverse effects of senescence on the innate and adaptive immune responses decrease the efficacy of vaccination and increase susceptibility to infectious, chronic, autoimmune, and neurodegenerative diseases (Castelo-Branco and Soveral, 2014).”
Background
Food nutrients as inherent sources of immunomodulation during COVID-19 pandemic
Vishwakarma, S., Panigrahi, C., Barua, S., Sahoo, M., & Mandliya, S. (2022) · LWT · doi:10.1016/j.lwt.2022.113154 · Cited by 59 · see citing works
“These secretions are carried out by two mechanisms viz. cell cytotoxicity and cytokine secretion and done by two main subpopulations, CD56dimCD16+ NK cells and CD56brightCD16- NK cells (Castelo-Branco & Soveral, 2014).”
BackgroundInfluential
Sex-Specific Immune Responses in Stroke
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Targeting Immune Senescence in Atherosclerosis
Vellasamy, D. M., Lee, S.-J., Goh, K. W., Goh, B. H., Tang, Y.-Q., Ming, L. C., & Yap, W. H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113059 · Cited by 60 · see citing works
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Analyses of 123 Peripheral Human Immune Cell Subsets: Defining Differences with Age and between Healthy Donors and Cancer Patients Not Detected in Analysis of Standard Immune Cell Types
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“Changes in the immune system with aging are evidenced by the observation that older individuals have a higher prevalence of autoimmunity, chronic diseases and cancer [32].”
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Comparative Study on the Structural Properties and Bioactivities of Three Different Molecular Weights of Lycium barbarum Polysaccharides
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Stromal Fibroblast in Age-Related Cancer: Role in Tumorigenesis and Potential as Novel Therapeutic Target
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Immunological alterations in frail older adults: A cross sectional study
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“The alterations that occur with aging, and that compromise the competence of immune system to generate specific responses to internal and external damaging agents, are defined as “immunosenescence” (Castelo-Branco and Soveral, 2014; de Araújo et al., 2013).”
Immunosenescence and lymphomagenesis
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“Concurrently, elevated levels of antiinflammatory cytokines, such as transforming growth factor (TGF)-β and IL-10, have been reported (Carrieri et al., 2004; Lio et al., 2004; Franceschi et al., 2007; Castelo-Branco and Soveral, 2014), which may regulate the inflammatory aging microenvironment.”
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Cell type–specific immune phenotypes predict loss of insulin secretion in new-onset type 1 diabetes
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“Immunological characteristics, including relative abundance of peripheral blood leukocyte populations, change with age (37, 38).”
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Frailty Status in Older Adults Is Related to Alterations in Indoleamine 2,3-Dioxygenase 1 and Guanosine Triphosphate Cyclohydrolase I Enzymatic Pathways.
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Muscle Mass and Inflammation in Older Adults: Impact of the Metabolic Syndrome
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Rabies pre-exposure prophylaxis elicits long-lasting immunity in humans
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“Immunosenescence and inflammation contributes to AD pathogenesis (Candore et al. 2010; Di Bona et al. 2010; Martorana et al. 2012; Michaud et al. 2013; Castelo-Branco and Soveral 2014; Fulop et al. 2015).”
Association between Active Helicobacter pylori Infection and Glaucoma: A Systematic Review and Meta-Analysis
Doulberis, M., Papaefthymiou, A., Pοlyzos, S. A., Bargiotas, P., Liatsos, C. N., Srivastava, D., Zavos, C., Katsinelos, P., & Kountouras, J. (2020) · Microorganisms · doi:10.3390/microorganisms8060894 · Cited by 43 · see citing works
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“As females age and estrogen levels decrease during reproductive senescence, there is a correlative functional decline in immune function, characterized by a persistent increase in proinflammatory factors (Castelo-Branco and Soveral, 2014).”
Associations between saliva and plasma cytokines in cognitively normal, older adults
Parkin, G. M., Kim, S., Mikhail, A. P., Malhas, R., McMillan, L. C., Hollearn, M. K., Granger, D. A., Mapstone, M. E., Yassa, M. A., & Thomas, E. A. (2022) · Aging Clinical and Experimental Research · doi:10.1007/s40520-022-02292-9 · Cited by 38 · see citing works
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Postoperative complications in elderly patients following pancreaticoduodenectomy lead to increased postoperative mortality and costs. A retrospective cohort study
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“Current studies have highlighted a more pronounced in ﬂ uence of aging on the adaptive immune system compared to the innate counterpart (27), and the impairment of immune surveillance will accelerate the accumulation of senescent cells and further expedite the aging process (28).”
Background
Improving the effectiveness of anti-aging modalities by using the constrained disorder principle-based management algorithms
Hurvitz, N., Elkhateeb, N., Sigawi, T., Rinsky‐Halivni, L., & Ilan, Y. (2022) · Frontiers in Aging · doi:10.3389/fragi.2022.1044038 · Cited by 36 · see citing works
“Inflamm-aging is associated with atherosclerosis, dementia, diabetes mellitus, cardiovascular changes, Alzheimer’s disease, Parkinson’s disease, depression, osteoarthritis, sarcopenia, and cancer (Castelo-Branco and Soveral, 2014; Franceschi et al., 2017b; Franceschi et al., 2018a; Franceschi et al., 2018b; Teodori et…”
Transcriptome analysis reveals immune-related gene expression changes with age in giant panda (Ailuropoda melanoleuca) blood
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Nuclear Sirtuins and the Aging of the Immune System
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“Indeed, this state of chronic inflammation, or inflammaging, is a typical feature of immunosenescence that actively contributes to the deterioration of immune and non-immune tissues [54].”
Background
Fat-Soluble Vitamins and the Current Global Pandemic of COVID-19: Evidence-Based Efficacy from Literature Review
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“1 3 decline in function of the immune system [44].”
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Causes and consequences of higher Leishmania infantum burden in patients with kala‐azar: a study of 625 patients
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“Infants have a dominant T-regulatory bias [36, 37], and CD8+ T-cell immunity is impaired to a greater extent in the elderly [38, 39], which may explain the higher parasitemia at the extremes of life.”
Background
Epigenetic age acceleration correlates with BMI in young adults
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“Age-related changes in inflammation are believed to contribute to increased risk of a myriad of comorbidities later in life, including diabetes, cardiovascular disease, and some cancers [26, 27].”
Background
Perspective: Role of Micronutrients and Omega-3 Long-Chain Polyunsaturated Fatty Acids for Immune Outcomes of Relevance to Infections in Older Adults—A Narrative Review and Call for Action
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“As regeneration capacity of cells and tissues decreases with age, barrier function weakens and hence is less efficient at preventing pathogen entry into the body (10).”
Prognostic role of pan‐immune‐inflammation value in patients with metastatic castration‐resistant prostate cancer treated with androgen receptor‐signaling inhibitors
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“Changes in both innate and adaptive immune systems with aging, and chronic low‐grade systemic inflammation causes an increase in the frequency of chronic diseases, especially cancer.(19,20) In the elderly population, inflammatory markers are associated with morbidity and mortality, including all‐cause death.”
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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