Immunobiography and the heterogeneity of immune responses in the elderly: A focus on inflammaging and trained immunity
Open accessAbstract
Owing to its memory and plasticity, the immune system (IS) is capable of recording all the immunological experiences and stimuli it was exposed to. The combination of type, dose, intensity, and temporal sequence of antigenic stimuli that each individual is exposed to has been named "immunobiography." This immunological history induces a lifelong continuous adaptation of the IS, which is responsible for the capability to mount strong, weak or no response to specific antigens, thus determining the large heterogeneity of immunological responses. In the last years, it is becoming clear that memory is not solely a feature of adaptive immunity, as it has been observed that also innate immune cells are provided with a sort of memory, dubbed "trained immunity." In this review, we discuss the main characteristics of trained immunity as a possible contributor to inflammaging within the perspective of immunobiography, with particular attention to the phenotypic changes of the cell populations known to be involved in trained immunity. In conclusion, immunobiography emerges as a pervasive and comprehensive concept that could help in understanding and interpret the individual heterogeneity of immune responses (to infections and vaccinations) that becomes particularly evident at old age and could affect immunosenescence and inflammaging.
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Franceschi et al. proposed the concept of "immunobiography," which considers the unique history of antigenic exposure that shapes an individual's immune system over time.
“To address this issue, Franceschi et al. proposed the concept of “immunobiography,” which considers the unique history of antigenic exposure that shapes an individual’s immune system over time.374”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [374]
Inflammaging is a chronic sterile inflammation with elevated IL-6, TNF, CXCL8, CCL2, CRP, and PLA2GD, linked to reduced myeloid DC and pDC numbers and function.
“Inflammaging is considered a chronic, sterile inflammation characterized by elevated levels of inflammatory mediators in the circulation including IL-6, TNF, CXCL8, CCL2, CRP, and PLA2GD”
From COVID-19 and the human innate immune system (2021) · cites this paper as Franceschi et al., 2017
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“proposed the concept of “immunobiography,” which considers the unique history of antigenic exposure that shapes an individual’s immune system over time.(374) While immunobiography provides a comprehensive framework for understanding immune aging, it does not take into account other factors that can influence the accum…”
BackgroundImmunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes?
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Self-citationDown syndrome, accelerated aging and immunosenescence
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Self-citationYarbro, J. R., Emmons, R. S., & Pence, B. D. (2020) · Immunometabolism · doi:10.20900/immunometab20200026 · Cited by 80 · see citing works
Macrophages in the cochlea; an immunological link between risk factors and progressive hearing loss
Hough, K., Verschuur, C. A., Cunningham, C. M., & Newman, T. A. (2021) · Glia · doi:10.1002/glia.24095 · Cited by 76 · see citing works
Munawara, U., Catanzaro, M., Xu, W., Tan, C., Hirokawa, K., Bosco, N., Dumoulin, D., Khalil, A., Larbi, A., Lévesque, S., et al. (2021) · Immunity & Ageing · doi:10.1186/s12979-021-00236-x · Cited by 74 · see citing works
The Aging Thyroid: A Reappraisal Within the Geroscience Integrated Perspective
Franceschi, C., Ostan, R., Mariotti, S., Monti, D., & Vitale, G. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00170 · Cited by 72 · see citing works
Self-citationSex and gender affect immune aging
Calabrò, A., Accardi, G., Aiello, A., Caruso, C., & Candore, G. (2023) · Frontiers in Aging · doi:10.3389/fragi.2023.1272118 · Cited by 71 · see citing works
Witkowski, J. M., Fülöp, T., & Bryl, E. (2022) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2022.111672 · Cited by 71 · see citing works
Immunosenescence, Inflammaging, and Lung Senescence in Asthma in the Elderly
Soma, T., & Nagata, M. (2022) · Biomolecules · doi:10.3390/biom12101456 · Cited by 71 · see citing works
Impact of Mesenchymal Stem Cell Senescence on Inflammaging
Lee, B.-C., & Yu, K. (2020) · BMB Reports · doi:10.5483/bmbrep.2020.53.2.291 · Cited by 70 · see citing works
Song, T., 昆明650223,中国, 中.-C., Zheng, H., Han, J.-B., Jin, L., Yang, X. S., Liu, F., Luo, R., Tian, R., Cai, H., et al. (2020) · 动物学研究 · doi:10.24272/j.issn.2095-8137.2020.202 · Cited by 62 · see citing works
Nonuniversality of inflammaging across human populations
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Self-citationHerpes Viruses and Senile Dementia: First Population Evidence for a Causal Link
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The dark side of Tregs during aging
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Marcon, G., Tettamanti, M., Capacci, G., Fontanel, G., Spanò, M., Nobili, A., Forloni, G., & Franceschi, C. (2020) · Aging · doi:10.18632/aging.103872 · Cited by 60 · see citing works
Self-citationTargeting 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
Trained Immunity: An Overview and the Impact on COVID-19
Brueggeman, J., Zhao, J., Schank, M., Yao, Z. Q., & Moorman, J. P. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.837524 · Cited by 57 · see citing works
CNS Ageing in Health and Neurodegenerative Disorders
Kesidou, E., Theotokis, P., Damianidou, O., Boziki, M. K., Konstantinidou, N., Taloumtzis, C., Sintila, S.-A., Grigoriadis, P., Evangelopoulos, M., Bakirtzis, C., et al. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12062255 · Cited by 57 · see citing works
Toward precision interventions and metrics of inflammaging
Franceschi, C., Olivieri, F., Moskalev, A., Ivanchenko, M., & Santoro, A. (2025) · Nature Aging · doi:10.1038/s43587-025-00938-7 · Cited by 59 · see citing works
Self-citationAge-related changes in the immune system and challenges for the development of age-specific vaccines
Doherty, M. T., Weinberger, B., Didierlaurent, A. M., & Lambert, P. (2025) · Annals of Medicine · doi:10.1080/07853890.2025.2477300 · Cited by 63 · see citing works
Aging and Options to Halt Declining Immunity to Virus Infections
Palacios-Pedrero, M. Á., Osterhaus, A. D. M. E., Becker, T., Elbahesh, H., Rimmelzwaan, G. F., & Saletti, G. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.681449 · Cited by 55 · see citing works
Immunosenescence and Altered Vaccine Efficiency in Older Subjects: A Myth Difficult to Change
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Self-citationNardini, C., Moreau, J., Gensous, N., Ravaioli, F., Garagnani, P., & Bacalini, M. G. (2018) · Seminars in Immunology · doi:10.1016/j.smim.2018.10.009 · Cited by 52 · see citing works
Self-citationThe peculiar aging of human liver: A geroscience perspective within transplant context
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Self-citationAn immunologist’s guide to immunosenescence and its treatment
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What if there’s no such thing as “aging”?
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The emerging role of T follicular helper (TFH) cells in aging: Influence on the immune frailty
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Ciabattini, A., Garagnani, P., Santoro, F., Rappuoli, R., Franceschi, C., & Medaglini, D. (2020) · Seminars in Immunopathology · doi:10.1007/s00281-020-00821-0 · Cited by 46 · see citing works
Self-citationOstan, R., Monti, D., Mari, D., Arosio, B., Gentilini, D., Ferri, E., Passarino, G., Rango, F. D., D’Aquila, P., Mariotti, S., et al. (2018) · The Journals of Gerontology Series A · doi:10.1093/gerona/gly194 · Cited by 42 · see citing works
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Inflammaging in Endemic Areas for Infectious Diseases
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Self-citationThe human immunosenescence phenotype: does it exist?
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Contribution of viral and bacterial infections to senescence and immunosenescence
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Immunosenescence: A Critical Factor Associated With Organ Injury After Sepsis
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The Human Body as a Super Network: Digital Methods to Analyze the Propagation of Aging
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Do vaccinations influence the development of Alzheimer disease?
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Risk Factors for Long COVID in Older Adults
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Inflammageing and clonal haematopoiesis interplay and their impact on human disease
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Age-Related Alterations in Immune Function and Inflammation: Focus on Ischemic Stroke
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- Authors
- Franceschi, C., Salvioli, S., Garagnani, P., de Eguileor, M., Monti, D., & Capri, M.
- Affiliations
- Istituto delle Scienze Neurologiche di Bologna (IT)
- University of Bologna (IT)
- University of Florence (IT)
- Corresponding author
- Salvioli, Stefano
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2017-08-15
- Volume
- 8
- Pages
- 982-982
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC5559470
- OpenAlex
- W2747602890
- Cited by
- 290
- References
- 127
- Citations by year
- 2026: 26 · 2025: 30 · 2024: 30 · 2023: 32 · 2022: 40 · 2021: 43 · 2020: 40 · 2019: 18 · 2018: 29 · 2017: 2
- FWCI
- 2.50
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by)
- Florence Research (University of Florence) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- IrInSubria (University of Insubria) (submittedVersion)
- Funders
- Seventh Framework Programme (602757)
- Horizon 2020 Framework Programme (634821)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- trained immunity, inflammaging, immunosenescence, immunological memory, vaccine response, infection response
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