Does the human immune system ever really become “senescent”?
Open accessAbstract
Like all somatic tissues, the human immune system changes with age. This is believed to result in an increased frequency of, and susceptibility to, infectious disease and to contribute to a wide range of non-communicable age-associated diseases in later life, especially cancer, cardiovascular disease, and autoimmunity. The majority of studies addressing immune ageing has been cross-sectional, but limited longitudinal studies are contributing to a better understanding of age-associated changes, as opposed to differences, and their clinical relevance. However, intriguing differences are emerging that implicate highly context-dependent immune ageing processes, mitigating against current generalisations concerning human immunosenescence and indicating the necessity for detailed comparisons of different populations, even those that would appear quite similar at first glance.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The pool of antigen-specific T cells may diminish over time.
“Immune memory can be very long lasting, providing protection against many infections for decades; however, people are living much longer than before, and the pool of antigen-specific T cells may diminish over time [36].”
From Immune function and micronutrient requirements change over the life course (2018) · cites this paper as [36]
Immune memory can be very long lasting, providing protection against many infections for decades.
“Immune memory can be very long lasting, providing protection against many infections for decades; however, people are living much longer than before, and the pool of antigen-specific T cells may diminish over time [36].”
From Immune function and micronutrient requirements change over the life course (2018) · cites this paper as [36]
Thymic involution and the relative paucity of naïve lymphocytes in older people means that they are less able to mount an adequate defense against neoantigens and thus exposure to them is more hazardous than in younger people.
“In addition, thymic involution and the relative paucity of naïve lymphocytes in older people means that they are less able to mount an adequate defense against neoantigens and thus exposure to them is more hazardous than in younger people [36].”
From Immune function and micronutrient requirements change over the life course (2018) · cites this paper as [36]
In older people, a lifetime of exposure to antigens and to numerous sources of oxidative stress can cause immune dysregulation that makes them more susceptible to infections than any other age group apart from young children.
“In older people, a lifetime of exposure to antigens and to numerous sources of oxidative stress can cause immune dysregulation that makes them more susceptible to infections than any other age group apart from young children [23,35,36].”
From Immune function and micronutrient requirements change over the life course (2018) · cites this paper as [36]
These factors may explain why older people have a poorer response to vaccines than the young.
“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 [36]
It is especially important to ensure that antioxidant levels (e.g., vitamins C, E, and A) and micronutrients that are components of antioxidant enzymes (e.g., zinc, copper, iron, and selenium) are sufficient to combat the oxidative stress that is induced by many lifestyle factors common in this group, and which has great impact on immune function.
“It is especially important to ensure that antioxidant levels (e.g., vitamins C, E, and A) and micronutrients that are components of antioxidant enzymes (e.g., zinc, copper, iron, and selenium) are sufficient to combat the oxidative stress that is induced by many lifestyle factors common in this group, and which has great impact on immune function [10,23,35,36,44].”
From Immune function and micronutrient requirements change over the life course (2018) · cites this paper as [36]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Telomeres shorten during ageing of human fibroblasts
Harley, C. B., Futcher, A. B., & Greider, C. W. (1990) · Nature · doi:10.1038/345458a0 · Cited by 5,750 · see citing works
Inflamm‐aging: An Evolutionary Perspective on Immunosenescence
FRANCESCHI, C., BONAFÈ, M., VALENSIN, S., OLIVIERI, F., DE LUCA, M., OTTAVIANI, E., & DE BENEDICTIS, G. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06651.x · Cited by 5,358 · see citing works
Cellular senescence and the senescent secretory phenotype: therapeutic opportunities
Tchkonia, T., Zhu, Y., van Deursen, J., Campisi, J., & Kirkland, J. L. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64098 · Cited by 1,774 · see citing works
Perforin and granzymes: function, dysfunction and human pathology
Voskoboinik, I., Whisstock, J. C., & Trapani, J. A. (2015) · Nature Reviews Immunology · doi:10.1038/nri3839 · Cited by 1,327 · see citing works
Proinflammatory Cytokines, Aging, and Age-Related Diseases
Michaud, M., Balardy, L., Moulis, G., Gaudin, C., Peyrot, C., Vellas, B., Cesari, M., & Nourhashemi, F. (2013) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2013.05.009 · Cited by 1,094 · see citing works
Quantification of biological aging in young adults
Belsky, D. W., Caspi, A., Houts, R., Cohen, H. J., Corcoran, D. L., Danese, A., Harrington, H., Israel, S., Levine, M. E., Schaefer, J. D., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1506264112 · Cited by 1,012 · see citing works
Donnelly, C. A., Ghani, A. C., Leung, G. M., Hedley, A. J., Fraser, C., Riley, S., Abu-Raddad, L. J., Ho, L.-M., Thach, T.-Q., Chau, P., et al. (2003) · The Lancet · doi:10.1016/s0140-6736(03)13410-1 · Cited by 940 · see citing works
Stem cell aging: mechanisms, regulators and therapeutic opportunities
Oh, J., Lee, Y. D., & Wagers, A. J. (2014) · Nature Medicine · doi:10.1038/nm.3651 · Cited by 796 · see citing works
Solana, R., Tarazona, R., Gayoso, I., Lesur, O., Dupuis, G., & Fulop, T. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.04.008 · Cited by 567 · see citing works
Shortage of circulating naive CD8+ T cells provides new insights on immunodeficiency in aging
Fagnoni, F. F., Vescovini, R., Passeri, G., Bologna, G., Pedrazzoni, M., Lavagetto, G., Casti, A., Franceschi, C., Passeri, M., & Sansoni, P. (2000) · Blood · doi:10.1182/blood.v95.9.2860.009k35_2860_2868 · Cited by 519 · see citing works
Wikby, A., Ferguson, F., Forsey, R., Thompson, J., Strindhall, J., Löfgren, S., Nilsson, B.-O., Ernerudh, J., Pawelec, G., & Johansson, B. (2005) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/60.5.556 · Cited by 407 · see citing works
Self-citationWertheimer, A. M., Bennett, M. S., Park, B., Uhrlaub, J. L., Martinez, C., Pulko, V., Currier, N. L., Nikolich-Žugich, D., Kaye, J., & Nikolich-Žugich, J. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1301721 · Cited by 352 · see citing works
Aspinall, R., & Andrew, D. (2000) · Journal of Clinical Immunology · doi:10.1023/a:1006611518223 · Cited by 315 · see citing works
An evolutionary perspective on the mechanisms of immunosenescence
Shanley, D. P., Aw, D., Manley, N. R., & Palmer, D. B. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.05.001 · Cited by 315 · see citing works
McElhaney, J. E., Zhou, X., Talbot, H. K., Soethout, E., Bleackley, R. C., Granville, D. J., & Pawelec, G. (2012) · Vaccine · doi:10.1016/j.vaccine.2012.01.015 · Cited by 229 · see citing works
Self-citationDOWD, J. B., AIELLO, A. E., & ALLEY, D. E. (2009) · Epidemiology and Infection · doi:10.1017/s0950268808000551 · Cited by 210 · see citing works
Fuertes Marraco, S. A., Soneson, C., Cagnon, L., Gannon, P. O., Allard, M., Maillard, S. A., Montandon, N., Rufer, N., Waldvogel, S., Delorenzi, M., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aaa3700 · Cited by 206 · see citing works
Derhovanessian, E., Maier, A. B., Hähnel, K., Beck, R., de Craen, A. J. M., Slagboom, P. E., Westendorp, R. G. J., & Pawelec, G. (2011) · Journal of General Virology · doi:10.1099/vir.0.036004-0 · Cited by 186 · see citing works
Self-citationHallmark Features of Immunosenescence Are Absent in Familial Longevity
Derhovanessian, E., Maier, A. B., Beck, R., Jahn, G., Hähnel, K., Slagboom, P. E., de Craen, A. J. M., Westendorp, R. G. J., & Pawelec, G. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001629 · Cited by 164 · see citing works
Self-citationEmerging concepts in tissue-resident T cells: lessons from humans
Thome, J. J. C., & Färber, D. L. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.05.003 · Cited by 144 · see citing works
McElhaney, J. E., Kuchel, G. A., Zhou, X., Swain, S. L., & Haynes, L. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00041 · Cited by 139 · see citing works
Di Benedetto, S., Derhovanessian, E., Steinhagen-Thiessen, E., Goldeck, D., Müller, L., & Pawelec, G. (2015) · Biogerontology · doi:10.1007/s10522-015-9563-2 · Cited by 131 · see citing works
Self-citationWeltevrede, M., Eilers, R., de Melker, H. E., & van Baarle, D. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2016.02.005 · Cited by 128 · see citing works
Continuous cytomegalovirus seroconversion in a large group of healthy blood donors
Hecker, M., Qiu, D.-Y., Marquardt, K., et al. (2004) · Vox Sanguinis · doi:10.1111/j.0042-9007.2004.00388.x · Cited by 124 · see citing works
The confounded effects of age and exposure history in response to influenza vaccination
Mosterín, A., McElhaney, J. E., Fonville, J. M., Powers, D. C., BEYER, W. E. P., & Smith, D. J. (2015) · Vaccine · doi:10.1016/j.vaccine.2015.11.058 · Cited by 112 · see citing works
Schulz, A. R., Mälzer, J. N., Domingo, C., Jürchott, K., Grützkau, A., Babel, N., Nienen, M., Jelinek, T., Niedrig, M., & Thiel, A. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500598 · Cited by 112 · see citing works
Hayflick, L. (1968) · Scientific American · doi:10.1038/scientificamerican0368-32 · Cited by 110 · see citing works
Ferrando‐Martínez, S., Romero-Sánchez, M. C., Solana, R., Delgado, J., de la Rosa, R., Muñoz‐Fernández, M. Á., Ruíz-Mateos, E., & Leal, M. (2011) · AGE · doi:10.1007/s11357-011-9341-2 · Cited by 107 · see citing works
HSC Aging and Senescent Immune Remodeling
Denkinger, M. D., Leins, H., Schirmbeck, R., Florian, M. C., & Geiger, H. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.10.008 · Cited by 105 · see citing works
Derhovanessian, E., Maier, A. B., Hähnel, K., McElhaney, J. E., Slagboom, E. P., & Pawelec, G. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1303361 · Cited by 93 · see citing works
Self-citationNK cells converge lytic granules to promote cytotoxicity and prevent bystander killing
Hsu, H., Mace, E. M., Carisey, A. F., Viswanath, D. I., Christakou, A. E., Wiklund, M., Önfelt, B., & Orange, J. S. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201604136 · Cited by 86 · see citing works
The SENIEUR protocol after 16 years
Pawelec, G., Ferguson, F. G., & Wikby, A. (2001) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(00)00240-2 · Cited by 83 · see citing works
Self-citationBlood-Borne Biomarkers of Mortality Risk: Systematic Review of Cohort Studies
Barron, E., Lara, J., White, M. J., & Mathers, J. C. (2015) · PLoS ONE · doi:10.1371/journal.pone.0127550 · Cited by 81 · see citing works
Complexity of Anti‐immunosenescence Strategies in Humans
Capri, M., Monti, D., Salvioli, S., Lescai, F., Pierini, M., Altilia, S., Sevini, F., Valensin, S., Ostan, R., Bucci, L., et al. (2006) · Artificial Organs · doi:10.1111/j.1525-1594.2006.00295.x · Cited by 81 · see citing works
Cell Therapy Strategies to Combat Immunosenescence
Stahl, E. C., & Brown, B. N. (2015) · Organogenesis · doi:10.1080/15476278.2015.1120046 · Cited by 73 · see citing works
Lymphocyte Count and Mortality Risk in Older Persons. The Leiden 85‐Plus Study
Izaks, G. J., Remarque, E. J., Becker, S. V., & Westendorp, R. G. J. (2003) · Journal of the American Geriatrics Society · doi:10.1046/j.1532-5415.2003.51467.x · Cited by 63 · see citing works
Effects of aging on human leukocytes (part I): immunophenotyping of innate immune cells
Stervbo, U., Meier, S., Mälzer, J. N., Baron, U., Bozzetti, C., Jürchott, K., Nienen, M., Olek, S., Rachwalik, D., Schulz, A. R., et al. (2015) · AGE · doi:10.1007/s11357-015-9828-3 · Cited by 59 · see citing works
Alam, I., Goldeck, D., Larbi, A., & Pawelec, G. (2012) · AGE · doi:10.1007/s11357-012-9455-1 · Cited by 47 · see citing works
Self-citationStervbo, U., Bozzetti, C., Baron, U., Jürchott, K., Meier, S., Mälzer, J. N., Nienen, M., Olek, S., Rachwalik, D., Schulz, A. R., et al. (2015) · AGE · doi:10.1007/s11357-015-9829-2 · Cited by 37 · see citing works
Adriaensen, W. J., Pawelec, G., Vaes, B., Hamprecht, K., Derhovanessian, E., Pottelbergh, G. V., Degryse, J., & Matheï, C. (2016) · The Journals of Gerontology Series A · doi:10.1093/gerona/glw215 · Cited by 27 · see citing works
Self-citationBetter immunity in later life: a position paper
Faragher, R., Frasca, D., Remarque, E. J., & Pawelec, G. (2014) · AGE · doi:10.1007/s11357-014-9619-2 · Cited by 11 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes?
Fulop, T., Larbi, A., Dupuis, G., Le Page, A., Frost, E. H., Cohen, A. A., Witkowski, J. M., & Franceschi, C. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01960 · Cited by 1,364 · see citing works
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
- Authors
- Pawelec, G.
- Affiliations
- King's College London (GB)
- Corresponding author
- Pawelec, Graham
- ORCID
- Pawelec, Graham
- Venue
- F1000Research
- Publisher
- F1000 Research Ltd
- Published
- 2017-08-04
- Volume
- 6
- Pages
- 1323
- ISSN
- 2046-1402 (ISSN-L)
- PMC
- PMC5553082
- OpenAlex
- W2744846584
- Cited by
- 45
- References
- 41
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 6 · 2020: 9 · 2019: 6 · 2018: 9 · 2017: 2
- FWCI
- 0.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- F1000Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Croeni Foundation (Educational Grant)
- Bundesministerium für Bildung und Forschung (BMBF 16SV5536K)
- European Commission (IDEAL, FP7 LIP F2-2011-259679)
- Deutsche Forschungsgemeinschaft (DFG PA 361/22)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- immunosenescence, human immune system, age-related diseases, infection susceptibility, cancer, cardiovascular disease, autoimmunity, longitudinal study, population differences
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
