Cited by 1,165T-cell and B-cell ImmunologyGenetics, Aging, and Longevity in Model OrganismsTelomeres, Telomerase, and Senescence

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The Aging Immune System: Primer and Prospectus

Miller, Richard A.·1996·Science

DOI 10.1126/science.273.5271.70

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Abstract

Changes in T lymphocyte populations underlie much of the age-related decline in the protective immune response. Aging leads to the replacement of virgin T cells by memory T cells and to the accumulation of cells with signal transduction defects. Studies of antibody gene assembly, accessory cell function, post-thymic T cell development, skewed selection of T cell receptor repertoire, and the clinical concomitants of immune senescence will shed new light on the causes and consequences of age-dependent immune failure.

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Gravekamp, C., Kim, S. H., & Castro, F. (2008) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2008.05.003 · Cited by 12
The effect of lipopolysaccharide on enhanced inflammatory process with age: Modulation of NF-κB
Kwon, H. J., Sung, B. K., Kim, J. W., Lee, J., Kim, N. D., Yoo, M. A., Kang, H. S., Baek, H. S., Bae, S.-J., Choi, J. S., et al. (2001) · AGE · doi:10.1007/s11357-001-0017-1 · Cited by 12
“physiological changes that take place as a consequence of aging is an impaired immune surveillance system to optimally monitor environmental stresses (6, 7).”
Background
Dwindling competition with constant demand: Can homeostatic adjustments explain age-associated changes in peripheral B cell selection?
Quinn, W. J., Scholz, J. L., & Cancro, M. P. (2005) · Seminars in Immunology · doi:10.1016/j.smim.2005.05.016 · Cited by 12
The importance of anti-insulin antibody in patients with type 1 diabetes mellitus treated with continuous subcutaneous insulin infusion or multiple daily insulin injections therapy
Sahin, S. B., Çetinkalp, Ş., Özgen, G., Saygılı, F., & Yılmaz, C. (2010) · Acta Diabetologica · doi:10.1007/s00592-010-0221-5 · Cited by 12
“bodies and delayed hypersensitivity responses [27].”
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Phosphorylation regulates mitochondrial glycerol-3-phosphate-1 acyltransferase activity in T-lymphocytes
Collison, L. W., & Jolly, C. A. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2005.12.002 · Cited by 12
Maturation of the mucosal immune system underlies colitis susceptibility in interleukin-10-deficient (IL-10−/−) mice
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“Although it is widely acknowledged that the immune system changes with age, reports attempting to define the specific immunologic changes attributable to normal aging vary widely in their findings [39].”
Background
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“The decline in the immune response toward infectious microbes in senescence is associated with a dysregulation of certain macrophage functions, such as NO release or a reduced generation of oxygen radicals (Ding et al. 1994; Miller 1996; Kissin et al. 1997).”
Background
Critical Illness in the Elderly: Review of Pathophysiology of Aging and Outcome of Intensive Care
Chelluri, L. (2001) · Journal of Intensive Care Medicine · doi:10.1177/088506660101600302 · Cited by 12
Stem Cells and Genetics in the Study of Development, Aging, and Longevity
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Characterization of an interaction between fetal hemoglobin and lipid A of LPS resulting in augmented induction of cytokine production in vivo and in vitro
Gorczynski, R. M., Alexander, C., Bessler, W. G., Fournier, K., Hoffmann, P., Mach, J. P., Ramakrishna, V., Rietschel, E., Song, L., Waelli, T., et al. (2004) · International Immunopharmacology · doi:10.1016/j.intimp.2004.08.006 · Cited by 12
Defect in ERK2 and p54JNK Activation in Aging Mouse Splenocytes
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“Indeed, it has been reported that stimulation of human B cells with either CaI or PMA alone can induce Tyr phosphorylation, as well as the enzymatic activation of ERK (34).”
Background
Interleukin-10 Enhances Immune Responses to Pneumococcal Polysaccharides and Sheep Erythrocytes in Young and Aged Mice
Luo, W., Fine, J., Garg, M., Kaplan, A. M., & Bondada, S. (1999) · Cellular Immunology · doi:10.1006/cimm.1999.1516 · Cited by 12
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Blood parasites in sympatric lizards: what is their impact on hosts’ immune system?
Damas‐Moreira, I., Maia, J. P. M. C., Tomé, B., Salvi, D., Perera, A., & Harris, D. J. (2022) · Amphibia-Reptilia · doi:10.1163/15685381-bja10078 · Cited by 11
“…not correlated with any circulating blood cell value and was found to be sig-niﬁcantly lower in larger individuals, although a decline in immune function as individuals grow older could be related to gradual alterations of the immune system and increased vulnerability to infections (Miller, 1996).”
Background
Immunological Biomarkers Determined In Female Rats Administered With Pro-Fertility Extract Of Anthocleista Vogelii
Oladimeji, S. O., Igbalaye, J. O., & Coleshowers, C. L. (2014) · Journals & Books Hosting (International Knowledge Sharing Platform) · Cited by 11
Evolutionary ecology of senescence: a case study using Tree Swallows, Tachycineta bicolor
Vleck, C. M., Vleck, D. B. V., & Palacios, M. G. (2011) · Journal für Ornithologie · doi:10.1007/s10336-010-0629-2 · Cited by 14
“The immune system is critical for survival and immunosenescence is thought to increase susceptibility to infection, autoimmune disease, and cancer (Miller 1996).”
Background
Visualization of Resident Memory CD8 T Cells in the Lungs of Young and Aged Influenza Memory Mice and after Heterosubtypic Challenge
Cookenham, T. S., Lanzer, K. G., Tighe, M., Ward, J. M., Reiley, W. W., & Blackman, M. A. (2021) · ImmunoHorizons · doi:10.4049/immunohorizons.2100032 · Cited by 11
Inactivated influenza vaccines
Keitel, W. A., & Couch, R. B. (2002) · Perspectives in medical virology · doi:10.1016/s0168-7069(02)07008-8 · Cited by 11
Immunopotentiating effect of a ‘Yang’‐promoting formula of traditional Chinese medicine on aged female BALB/c mice
Zhang, L., Wang, Y., Wang, L., & Gao, X. (2004) · Phytotherapy Research · doi:10.1002/ptr.1551 · Cited by 11
The Immune Response of Larvae and Pupae of Calliphora vicina (Diptera: Calliphoridae), upon Administered Insult with Escherichia coli
Crowley, L. D., & Houck, M. A. (2002) · Journal of Medical Entomology · doi:10.1603/0022-2585-39.6.931 · Cited by 11
The significance of mycobacterium tuberculosis antibody, antigen 60 IgG in patients with abnormal chest radiography.
Wu, H.-P., Shieh, W.-B., Hsien, F.-K., & Hua, C. (2004) · PubMed · Cited by 11
Nutrition and the Aging Immune Response
Adolfsson, O., & Meydani, S. N. (2002) · KARGER eBooks · doi:10.1159/000061860 · Cited by 11
“and the production of and responsiveness to interleukin 2 (IL-2), a major T cell growth factor that regulates clonal expansion of T cells during the immune response [7].”
Background
Analysis of the TCRBV Repertoire of T Cells in Normal, Human Skin: Evidence for a Restricted Diversity
Menssen, A., Vollmer, S., Trommler, P., Sander, C. A., & Prinz, J. C. (2000) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2000.00982.x · Cited by 11
Approach to the problem of pneumonia in long-term care facilities
Muder, R. R. (2000) · Comprehensive Therapy · doi:10.1007/s12019-000-0027-4 · Cited by 11
Possible factors affecting response to intravesical bacillus Calmette-Guérin (Tokyo 172 Strain) therapy for carcinoma in situ of the bladder: A multivariate analysis
Takashi, M., Katsuno, S., Yuba, H., Ohshima, S., Wakai, K., & Ohno, Y. (1998) · International Urology and Nephrology · doi:10.1007/bf02564859 · Cited by 11
“It is generally agreed that T cell responses in elderly men become reduced [25, 26 ].”
Background
Aging Impairs Induction of Cyclin-Dependent Kinases and Down-Regulation of p27 in Mouse CD4+ Cells
Tamir, A., & Miller, R. A. (1999) · Cellular Immunology · doi:10.1006/cimm.1999.1573 · Cited by 11
Self-citation
The correlation between immunocompetence and an ornament trait changes over lifetime in Panorpa vulgaris scorpionflies
Kurtz, J. (2007) · Zoology · doi:10.1016/j.zool.2007.07.001 · Cited by 10
Age-Associated Remodeling of Neural and Nonneural Thymic Catecholaminergic Network Affects Thymopoietic Productivity
Leposavić, G., Pilipović, I., & Nanut, M. P. (2011) · NeuroImmunoModulation · doi:10.1159/000329499 · Cited by 11
Effects of low‐intensity physical exercise on acute changes in resting saliva secretory IgA levels in the elderly
Sakamoto, Y., Ueki, S., Shimanuki, H., Kasai, T., Takato, J., Ozaki, H., Kawakami, Y., & Haga, H. (2005) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/j.1447-0594.2005.00297.x · Cited by 10

Authors: Miller, R. A.
Affiliations: University of Michigan (US)
Corresponding author: Miller, Richard A.
ORCID: Miller, Richard A.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1996-07-05
Volume: 273
Issue: 5271
Pages: 70-74
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.273.5271.70
OpenAlex: W2043464691
Cited by: 1,165
References: 71
Citations by year: 2026: 7 · 2025: 7 · 2024: 15 · 2023: 19 · 2022: 9 · 2021: 22 · 2020: 34 · 2019: 25 · 2018: 33 · 2017: 32 · 2016: 24 · 2015: 31 · 2014: 26 · 2013: 40 · 2012: 35
FWCI: 5.20
Type: journal article
Language: en
Open access: closed
Locations: Science (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 › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Keywords: immunosenescence, aging, T cells, memory T cells, T cell receptor repertoire, signal transduction defects, accessory cell function, age-related immune decline
MeSH terms: Aged, Aged, 80 and over, Aging, Animals, Antibody Formation, Antigen-Presenting Cells, B-Lymphocytes, Cytotoxicity, Immunologic, Disease Susceptibility, Humans, Immune System, Immunologic Memory, Killer Cells, Natural, Longevity, Receptors, Antigen, T-Cell, T-Lymphocytes

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The Aging Immune System: Primer and Prospectus

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