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The Impact of Immune System Aging on Infectious Diseases
Open accessAbstract
Immune system aging is becoming a field of increasing public health interest because of prolonged life expectancy, which is not paralleled by an increase in health expectancy. As age progresses, innate and adaptive immune systems undergo changes, which are defined, respectively, as inflammaging and immune senescence. A wealth of available data demonstrates that these two conditions are closely linked, leading to a greater vulnerability of elderly subjects to viral, bacterial, and opportunistic infections as well as lower post-vaccination protection. To face this novel scenario, an in-depth assessment of the immune players involved in this changing epidemiology is demanded regarding the individual and concerted involvement of immune cells and mediators within endogenous and exogenous factors and co-morbidities. This review provides an overall updated description of the changes affecting the aging immune system, which may be of help in understanding the underlying mechanisms associated with the main age-associated infectious diseases.
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![Figure 2 Main qualitative age-associated changes in the cells of innate and adaptive immunity [13,28,29,32,35,37,39,40,41,42,43,44,45,46,49,50,51].](/paper-figures/7e0d4cec679348fe9764baedeb5dd63b/the-impact-of-immune-system-aging-on-infectious-diseases-figure-2.jpg)
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From The Environmental Determinants of Skin Health: Linking Climate Change, Air Pollution, and the Dermatologic Disease Burden (2025) · cites this paper as [88]
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“Furthermore, as impaired innate and adaptive immune responses make the elderly more vulnerable to pathogens and decreases the effectiveness of many vaccines (28).”
Aging and DNA Damage: Investigating the Microbiome’s Stealthy Impact – A Perspective
Chakrabarti, S. K., & Chattopadhyay, D. (2025) · Exploratory Research and Hypothesis in Medicine · doi:10.14218/erhm.2024.00046 · Cited by 2
“164–166 New research emphasizes the considerable role that imbalances in gut microbiota play in the processes associated with aging.”
Leang, C., Suwannatrai, A., Suttiprapa, S., Laha, T., & Sripa, B. (2025) · Tropical medicine & international health · doi:10.1111/tmi.14100 · Cited by 2
“…to other family members ( p = 0.02), suggesting that occupational exposures and behavioural factors specific to this role, such as increased involvement in agricultural activities or greater exposure to contaminated environments, as mentioned above, may contribute to their increased risk [28, 29].”
InfluentialSpeckled-egg staining appearance of cryptococcal osteomyelitis in an immunocompetent patient
Stack, M. A., Lavik, J.-P., Schneider, J. G., & Cross, B. (2025) · IDCases · doi:10.1016/j.idcr.2025.e02171 · Cited by 2
“Advanced age is a risk factor not only for cryptococcal infection, but other infections as well due to immunosenescence from an aging immune system [12,13].”
Deckers, J., van Elsas, Y., Versteeg, I., Anbergen, T., Toner, Y. C., Grao-Roldán, C., Cole, J. E., Umali, M., Wang, W., Nauta, S. A., et al. (2026) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2026.101660
Nagappan, G. L., Antony, A. M., Venkateswaran, R., & Thirunavukkarasu, R. (2026) · IP International Journal of Medical Microbiology and Tropical Diseases · doi:10.18231/j.ijmmtd.16720.1784528227 · Cited by 1
“31 Several studies evaluating SSI risk factors are limited by single-center design, heterogeneous patient populations, and variations in wound classification systems.”
Vaccines for the Prevention of COVID-19 in Older Adults
Olagunju, O. J., Oyebanji, O. A., Mylonakis, E. E., & Canaday, D. H. (2026) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2025.09.003 · Cited by 1
Reinstrup, N. W., Gidsel, R. H., Heikkinen, T., Dyrhol-Riise, A., Levin, L., Østergaard, L., & Ehlers, L. (2026) · Vaccines · doi:10.3390/vaccines14080703 · Cited by 1
Bhavya, R., & Sandur, R. (2026) · Immunological Investigations · doi:10.1080/08820139.2026.2695165 · Cited by 1
“…related signalling and senescence associated secretory phenotype (SASP) promote chronic low-grade inflammation (inflammaging) attenuating immune activity (Allameen et al., 2025; Kamroo et al., 2025; Mohapatra et al., 2023; Quiros-Roldan et al., 2024; Rea et al., 2018; Swanson et al., 2019).”
Thomas, S., van Haren, S. D., & Levy, O. (2026) · Current Opinion in Virology · doi:10.1016/j.coviro.2026.101557 · Cited by 2
Immune interplay between sepsis and haematological malignancies
Pons, S., Grosset, M., Touze, E., & Zafrani, L. (2026) · Intensive Care Medicine Experimental · doi:10.1186/s40635-026-00904-6 · Cited by 1
Yadav, A., Rana, M. J., & Rahaman, M. (2026) · Discover Public Health · doi:10.1186/s12982-026-01947-6 · Cited by 1
Ramadhan, A. F., Sutandhio, S., Darmadi, E. T., Wihanto, L., & Tanudjaja, G. N. (2026) · JUKEJ : Jurnal Kesehatan Jompa · doi:10.57218/jkj.vol5.iss1.2397 · Cited by 1
Typhoid fever in the West Gonja Municipality, Ghana: Analysis of 2022 laboratory surveillance data
Saeed, F. U., Apetorgbor, S. J., Issahaku, G. R., Akowuah, G., Odikro, M., Kenu, E., Nindow, J. A. C., & Kubio, C. (2026) · Journal of Interventional Epidemiology and Public Health · doi:10.37432/jieph-d-24-02048 · Cited by 1
Testing the redox theory of aging under parasitism
Silva, L. M., Belli, A., & Koella, J. C. (2026) · npj Aging · doi:10.1038/s41514-026-00357-x
“Contrary to the expectation that infection accelerates physiological decline 24 , parasite exposure increased longevity in both sexes.”
Zhang, Y.-Y., Zhang, Y.-W., Zhou, F., Chen, S., Dai, D., Li, C., Duan, Y., & Liu, M. (2025) · BMC Public Health · doi:10.1186/s12889-025-25970-5 · Cited by 1
“…respiratory infections accounted for the majority of cases among individuals over 55 years old, which is closely linked to age-related immune decline [22] and the higher prevalence of chronic respiratory diseases (e.g., Chronic Obstructive Pulmonary Disease (COPD), asthma) in this cohort [23].”
Jin, J., Hu, Y., & Lianxing, D. U. (2025) · Health Science Reports · doi:10.1002/hsr2.71639
“However, related studies [40–42] revealed that age widely influenced the susceptibility to pathogen infections, and there were marked differences in susceptibility and immune responses across age groups.”
Quantification of the IgG antibody response half-life for hybrid immunity to SARS-CoV-2
Bongiovanni, F., Conway, E. J., Smith, L., Cumming, J., Mazhari, R., Kiernan‐Walker, N., Eriksson, E. M., McVernon, J., & Müeller, I. (2025) · BMC Medicine · doi:10.1186/s12916-025-04490-4 · Cited by 1
Zhang, Y., Lou, C., Mao, L., Yao, W., Ma, C., Shi, X., Qin, F., & Zhang, R. (2025) · BMC Women s Health · doi:10.1186/s12905-025-04119-x · Cited by 1
“The increase in middle-aged and older populations may be attributable to immunosenescence, which heightens infection risk [39].”
Gushchin, V., Semenenko, T., Burtseva, E., Simakova, Y., Ogarkova, D., Nozdracheva, A., Gotvyanskaya, T. P., Ermakova, T. V., Vetrova, E. V., Mukasheva, E. A., et al. (2025) · Epidemiology and Vaccinal Prevention · doi:10.31631/2073-3046-2025-24-4-14-30 · Cited by 1
A bibliometric analysis of the immune system and cognitive impairment: trends from 1985 to 2024
Zou, B., Xiang, J., Zhang, M., Huang, J., & Feng, C. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1587575 · Cited by 2
Ramly, N., Muhammad, E. N., Asari, F. N., Mutalip, M. H. A., Hisham, M. F. M., Haris, H. M., & Chong, Z. L. (2025) · Clinical Epidemiology and Global Health · doi:10.1016/j.cegh.2025.102152 · Cited by 1
Alyazidi, A., Muthanna, A., Noor, S. M., Osman, M., & Seman, Z. (2025) · Malaysian Journal of Social Sciences and Humanities · doi:10.47405/mjssh.v10i5.3382 · Cited by 1
“Collaborative interlaboratory studies, such as those conducted under ISO standards for bacterial quantification, demonstrate how pooling resources and standardizing protocols can improve reproducibility and reliability across diverse settings (Quiros-Roldan et al., 2024).”
Amewu, E., Amaglo, B., Osei-Poku, P., Abakah, A., Shardow, A. L. K., Wright, L., & Kwarteng, A. (2025) · PLoS ONE · doi:10.1371/journal.pone.0320640 · Cited by 1
“This relationship may be attributed to the cumulative effects of chronic infections and the natural decline in immune function that occurs with aging [41].”
Manzo, C., Isetta, M., & Castagna, A. (2024) · Rheumatology · doi:10.5114/reum/194687 · Cited by 1
“Immunosenescence, the progressive decline in the immune system functions associated with aging, can favour – among other consequences – an increase of incidence and severity of infections [70, 71].”
Bricout, H., LEVANT, M.-C., Crépey, P., Gavazzi, G., Gaillat, J., Dufournet, M., Assi, N., Grenier, B., RAGUIDEAU, F., Péretz, F., et al. (2025) · Influenza and Other Respiratory Viruses · doi:10.1111/irv.70193 · Cited by 1
Human Metapneumovirus: A Comprehensive Review of Etiology and Pathogenesis
Asif, M., Ullah, I., Aziz, M., Zubair, M., Ramzan, A., Nadeem, M., M.A.Dahesh, S., & Aziz, M. (2025) · Journal of Chemical Health Risks · doi:10.52783/jchr.v15.i3.8132 · Cited by 1
Invasive guests: the role of non-oral bacteria in oral dysbiosis and systemic health
Ari, M. M., Al‐Ahmad, A., Cieplik, F., & Scholz, K. J. (2026) · Journal of Oral Microbiology · doi:10.1080/20002297.2026.2745592
“Oral carriage rates vary widely, ranging from 24 to 84% in healthy adults [108] and approximately 48% in denture wearers [109], with older adults being particularly vulnerable due to age ‑ related immune decline, chronic conditions, medications, or nutritional deficiencies [110].”
Triggers and Modifiers of Acute Coronary Events and Implications for Practice: An Umbrella Review
Hunt, L., Riegel, M., Tofler, G. H., Heighes, P. T., Shi, W., & Buckley, T. A. (2026) · Journal of Advanced Nursing · doi:10.1111/jan.70777
Ebob, A. O. B., Gandjui, N. T. V., Lenz, B., Ouam, E., Foyet, J., Beng, A. A., Fombad, F. F., Nietcho, F., Ritter, M., Karunakaran, I., et al. (2026) · PLoS Neglected Tropical Diseases · doi:10.1371/journal.pntd.0014780
Preservation of MHC-Ia protective allele suppression of SIVmac239 in aged rhesus macaques
Marenco, A., Varco-Merth, B. D., Nkoy, C., Aparna, G., Lam, A., Li, H., Fachko, D. N., Duell, D. M., Goodwin, W., Ogunwale, O., et al. (2026) · The Journal of Immunology · doi:10.1093/jimmun/vkag272
Maiti, S., Lu, T., Dietz, Z. K., Whittier, S. K., Picking, W. D., & Picking, W. L. (2026) · Infection and Immunity · doi:10.1128/iai.00355-26
Chan, M. K. S., Skutella, T., Thomas, F. M., Lakey, J. R. T., Mutto, A. Á., Fukuda, K., Baochi, L., & Wong, M. B. F. (2026) · Frontiers in Veterinary Science · doi:10.3389/fvets.2026.1919982
“Immune competence, inflammatory regulation, age, co-infections, metabolic status and environmental stress can affect disease severity (80).”
Zhao, R., Zhao, M., Wang, Y., Zhang, X., Zhang, J., Ge, J., Jian-xing, Y. U. E., Xu, Y., & Liu, Q. (2026) · British Journal of Hospital Medicine · doi:10.31083/bjhm58253
Park, S. J., Choi, J. W., Choi, H., Im, G. E., Seo, B. H., Kim, H. E., Park, K.-B., Kim, S. A., Jung, J., Choi, M., et al. (2026) · Journal of Microbiology and Biotechnology · doi:10.4014/jmb.2607.07022
Derijks, L., Karapinar-Çarkıt, F., Mujagić, Z., van Marum, R. V., & Pierik, M. (2026) · Drugs & Aging · doi:10.1007/s40266-026-01321-w
“In parallel, immunosenescence and inflammaging may increase susceptibility to viral and opportunistic infections and may amplify class-specific adverse effects, such as HZ with JAK inhibition and initiation-related conduction effects with S1P receptor modulators [37, 69, 81, 88, 89].”
The Role of the Mammalian Target of Rapamycin in Microglial Phenotypic Polarization
Partridge, K. J., & Ebert, A. D. (2026) · Cells · doi:10.3390/cells15181654
“This may be particularly relevant for neuroinflammatory disease where long-term treatment may be required, and where patients may have age-related risks for metabolic comorbidities or vulnerability to infection [133,134].”
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Chaudhari, H. R., & Tonde, T. (2026) · Medical Journal Armed Forces India · doi:10.1016/j.mjafi.2026.08.003
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“Owners completed the Canine Dementia Scale (CADES 32 ) questionnaire along with others related to general health (study-specific), pain (LOAD, 37 CBPI 38 ), quality of life (adapted CORQ 39 , 40 ), sleep quality (Snore3.”
Maina, E., Ndung’u, P., Karanja, P., & Moriasi, G. A. (2026) · IJID Regions · doi:10.1016/j.ijregi.2026.100998
“Additional host factors contributing to increased risk among the elderly include reduced gastric acidity, impaired gut motility, and intestinal microbiome dysbiosis [ 10 , 11 ].”
Age- and sex-dependent heterogeneity during LPS-induced murine acute lung injury
Crispens, C., Wilken-Schmitz, A., Dern, V., Rahimi, A. R., Madau, E., Frigger, N. C., Jakob, J., Häupl, B., Oellerich, T., Weigert, A., et al. (2026) · Immunity & Ageing · doi:10.1186/s12979-026-00592-6
“These processes collectively contribute to the chronic low-grade inflammatory state termed inflammageing , which substantially modifies host responses to acute inflammatory injury [14–21, 29, 30, 52, 53].”
Application of artificial intelligence in geriatric infection: recent advances and prospects
Liang, P., Tan, Z., Liang, B., Xu, Y., Wang, T., Zhang, Z., & Cai, Y. (2026) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2026.1887322
Zailan, N. F. Z., Chee, H. Y., Tohit, E. R. M., Abdullah, M., Nordin, S. A., Ismail, I. Z., & Hassan, M. (2026) · Journal of Applied Toxicology · doi:10.1002/jat.70380
Quatorze, J., Reis, M., Alvarez1, G., & Martins, A. C. (2026) · Sensors · doi:10.3390/s26144616
“Other common age-related changes include declines in memory and information processing speed, as well as alterations in sexual, neurological, endocrine, cardiopulmonary, gastrointestinal, urinary [5,16], and immune system functions [17].”
Salam, T., Tufael, Siddique, M. A. B., Bari, K. F., Mujahid, M. H., Debnath, A., Nath, N. D., Ullah, M. S., & Upadhye, V. J. (2026) · BMC Microbiology · doi:10.1186/s12866-026-05292-1
Metadata
- Authors
- Quiros-Roldan, E., Sottini, A., Natali, P. G., & Imberti, L.
- Affiliations
- Department of Infectious and Tropical Diseases, ASST- Spedali Civili and DSCS- University of Brescia, 25123 Brescia, Italy
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT)
- Mediterranean Task Force for Cancer Control (MTCC), Via Pizzo Bernina, 14, 00141 Rome, Italy
- University of Brescia (IT)
- Corresponding author
- Imberti, Luisa
- Venue
- Microorganisms
- Publisher
- MDPI AG
- Published
- 2024-04-11
- Volume
- 12
- Issue
- 4
- Pages
- 775
- ISSN
- 2076-2607 (ISSN-L)
- PMC
- PMC11051847
- OpenAlex
- W4394716887
- Cited by
- 133
- References
- 270
- Citations by year
- 2026: 56 · 2025: 63 · 2024: 14
- FWCI
- 5.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Microorganisms (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Funders
- 2nd bando Sanità; PNRR-Salute; Ministero della Salute, Italia
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- immunosenescence, inflammaging, opportunistic infections, viral infection, bacterial infection, vaccine response in the elderly, innate immunity, adaptive immunity, comorbidities
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