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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Nishioka, T., Shimizu, J., Iida, R., Yamazaki, S., & Sakaguchi, S. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.11.6586 · Cited by 220
“Discussion It is well established that CD4 T cell function in response to Ag declines with aging (20).”
Background
Neutrophil ageing and immunesenescence
Lord, J. M., Butcher, S. K., Killampalli, V. V., Lascelles, D., & Salmon, M. (2001) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00285-8 · Cited by 218
Viral Pneumonia in Older Adults
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“to increased morbidity (table 1) [1–3].”
Apoptosis in the aging process
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“The decline in T-cell function is considered to play a role in the age-related increase in morbidity and mortality in elderly individuals during infection, age-enhanced susceptibility to autoimmunity, and cancer (Aggarwal and Gupta 1998; Miller 1996; Nagel et al. 1988).”
Background
A Case-Control Study of Acute Respiratory Tract Infection in General Practice Patients in The Netherlands
van Gageldonk‐Lafeber, A. B., Heijnen, M.-L. A., Bartelds, A. I. M., Peters, M., van der Plas, S. M., & Wilbrink, B. (2005) · Clinical Infectious Diseases · doi:10.1086/431982 · Cited by 210
“Although respiratory viruses are known to cause substantial morbidity in elderly people, no increase in the incidence of GP consultations was seen in our study [3, 25].”
Background
Immunological Responses to Exogenous Insulin
Fineberg, S. E., Kawabata, T. T., Finco‐Kent, D., Fountaine, R. J., Finch, G. L., & Krasner, A. S. (2007) · Endocrine Reviews · doi:10.1210/er.2007-0002 · Cited by 212
Association between natural killer cell activity and infection in immunologically normal elderly people
Ogata, K., An, E., Shioi, Y., Nakamura, K., Luo, S., Yokose, N., Minami, S., & Dan, K. (2001) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.2001.01571.x · Cited by 207
Developmental Origin Governs CD8+ T Cell Fate Decisions during Infection
Smith, N. L., Patel, R. K., Reynaldi, A., Grenier, J. K., Wang, J., Watson, N. B., Nzingha, K., Mon, K. J. Y., Peng, S. A., Grimson, A., et al. (2018) · Cell · doi:10.1016/j.cell.2018.05.029 · Cited by 202
“For example, previous work has indicated that the elderly respond poorly to vaccines because their CD8+ T cells become senescent (Miller, 1996).”
Result
Ageing and the neutrophil: no appetite for killing?
Butcher, S. K., Chahel, H., & Lord, J. M. (2000) · Immunology · doi:10.1046/j.1365-2567.2000.00079.x · Cited by 200
Functional properties of CD4+CD28− T cells in the aging immune system
Weyand, C. M., Brandes, J. C., Schmidt, D., Fulbright, J. W., & Goronzy, J. J. (1998) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(97)00161-9 · Cited by 201
B cells and aging: molecules and mechanisms
Cancro, M. P., Hao, Y., Scholz, J. L., Riley, R. L., Frasca, D., Dunn-Walters, D. K., & Blomberg, B. B. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.04.005 · Cited by 198
“Advancing age yields numerous immune system changes, in aggregate termed immunosenescence [1–5].”
Background
Aged BALB/c Mice as a Model for Increased Severity of Severe Acute Respiratory Syndrome in Elderly Humans
Roberts, A., Paddock, C. D., Vogel, L., Butler, E. L., Zaki, S. R., & Subbarao, K. (2005) · Journal of Virology · doi:10.1128/jvi.79.9.5833-5838.2005 · Cited by 196
“A number of defects in innate and adaptive immune responses have been described to occur during immune senescence in mice and humans (3, 10, 18, 21, 25, 26, 35).”
Background
Effective nasal influenza vaccine delivery using chitosan
Read, R. C., Naylor, S. C., Potter, C. W., Bond, J., Jabbal‐Gill, I., Fisher, A. N., Illum, L., & Jennings, R. (2005) · Vaccine · doi:10.1016/j.vaccine.2005.04.021 · Cited by 194
Subcellular Localization, Stoichiometry, and Protein Levels of 26 S Proteasome Subunits in Yeast
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Diagnosis of Respiratory Syncytial Virus Infection: Comparison of Reverse Transcription-PCR to Viral Culture and Serology in Adults with Respiratory Illness
Falsey, A. R., Formica, M. A., & Walsh, E. E. (2002) · Journal of Clinical Microbiology · doi:10.1128/jcm.40.3.817-820.2002 · Cited by 195
“Although there are no specific data regarding age-related differences in immunity to RSV, it is well documented that cellular immunity diminishes with aging (9).”
Background
The Combination of Donor and Recipient Age is Critical in Determining Host Immunoresponsiveness and Renal Transplant Outcome
Tullius, S. G., Tran, H., Guleria, I., Malek, S. K., Tilney, N. L., & Milford, E. L. (2010) · Annals of Surgery · doi:10.1097/sla.0b013e3181f65c7d · Cited by 193
“Aging of the immune system is a complex process leading to fundamental changes of all immune components.(5) Yet data on the age-associated immune responses after organ transplantation remain scarce and consequences of recipient age on graft function remain controversial.”
Background
Exercise and Psychosocial Factors Modulate Immunity to Influenza Vaccine in Elderly Individuals
Kohut, M. L., Cooper, M. M., Nickolaus, M. S., Russell, D. R., & Cunnick, J. E. (2002) · The Journals of Gerontology Series A · doi:10.1093/gerona/57.9.m557 · Cited by 193
Mechanisms Underlying T Cell Immunosenescence: Aging and Cytomegalovirus Infection
Tu, W., & Rao, S. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.02111 · Cited by 192
“Changes in T cell immunity appear to be have the most impact (Miller, 1996; Cambier, 2005).”
Background
Age-associated changes in immune and inflammatory responses: impact of vitamin E intervention
Wu, D., & Meydani, S. N. (2008) · Journal of Leukocyte Biology · doi:10.1189/jlb.0108023 · Cited by 188
“Although an age-related decrease in T cell function has been observed in memory [44, 47, 48] and naı̈ve [49–51] T cells, one of the hallmarks of age-related changes is a shift toward greater proportions of antigen-experienced memory T cells and a smaller proportion of naı̈ve T cells [3, 52, 53].”
Background
Constitutive activation of NF-kappa B in an animal model of aging
SPENCER, N. F. L. (1997) · International Immunology · doi:10.1093/intimm/9.10.1581 · Cited by 187
Increased TNF-α-Induced Apoptosis in Lymphocytes from Aged Humans: Changes in TNF-α Receptor Expression and Activation of Caspases
Aggarwal, S., Gollapudi, S. V. S., & Gupta, S. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.4.2154 · Cited by 252
Circulatory miR-34a as an RNA-based, noninvasive biomarker for brain aging
Li, X., Khanna, A., Li, N., & Wang, E. (2011) · Aging · doi:10.18632/aging.100371 · Cited by 184
“The list of genetic factors pertinent to life‐span determination has been growing by leaps and bounds, to define age‐related physiological changes [1].”
Background
Aging-related Deficiency of CD28 Expression in CD4+ T Cells Is Associated with the Loss of Gene-specific Nuclear Factor Binding Activity
Vallejo, A. N., Nestel, A. R., Schirmer, M., Weyand, C. M., & Goronzy, J. J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.14.8119 · Cited by 179
Reduction of Immunocompetent T Cells Followed by Prolonged Lymphopenia in Severe Sepsis in the Elderly*
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Long-lasting alterations of the immune system by ionizing radiation exposure: Implications for disease development among atomic bomb survivors
Kusunoki, Y., & Hayashi, T. (2007) · International Journal of Radiation Biology · doi:10.1080/09553000701616106 · Cited by 179
“In the elderly, the naı̈ve T-cell pool decreases due to reduced production of new T cells in the thymus so that responses to antigens are impaired when compared with younger individuals (Miller 1996, Mackall & Gress 1997, Rufer et al. 2001) (Figure 2B).”
Background
Replicative Senescence and Oxidant‐Induced Premature Senescence: Beyond the Control of Cell Cycle Checkpoints
Chen, Q. M. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06640.x · Cited by 176
Development of an Unrelated Donor Selection Score Predictive of Survival after HCT: Donor Age Matters Most
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A dilemma for mucosal vaccination: efficacy versus toxicity using enterotoxin-based adjuvants
Fujihashi, K., Koga, T., van Ginkel, F. W., Hagiwara, Y., & McGhee, J. R. (2002) · Vaccine · doi:10.1016/s0264-410x(02)00155-x · Cited by 175
Geriatric Respiratory Medicine
Chan, E. D., & Welsh, C. H. (1998) · CHEST Journal · doi:10.1378/chest.114.6.1704 · Cited by 170
Dehydroepiandrosterone as a regulator of immune cell function
Hazeldine, J., Arlt, W., & Lord, J. M. (2010) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2009.12.016 · Cited by 173
Age‐associated increases in oxidative stress and nuclear transcription factor κB activation are attenuated in rat liver by regular exercise
Radak, Z. O., Chung, H. Y., Naıto, H., Takahashi, R., Jung, K. J., Kim, H., & Goto, S. (2004) · The FASEB Journal · doi:10.1096/fj.03-0509fje · Cited by 173
Age-related modifications of the human alphabeta T cell repertoire due to different clonal expansions in the CD4+ and CD8+ subsets
Wack, A. (1998) · International Immunology · doi:10.1093/intimm/10.9.1281 · Cited by 173

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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