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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Background
An investigation of vago-regulatory and health-behavior accounts for increased inflammation in posttraumatic stress disorder
Dennis, P. A., Weinberg, J. B., Calhoun, P. S., Watkins, L. L., Sherwood, A., Dennis, M. F., & Beckham, J. C. (2016) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2016.02.008 · Cited by 28
“, prednisone) were covaried, given their associations with cytokine levels [28,55,56].”
Background
The NPY effects on murine leukocyte adherence and chemotaxis change with age
Medina, S., Rio, M. D., Hernánz, Á., & la Fuente, M. D. (2000) · Regulatory Peptides · doi:10.1016/s0167-0115(00)00134-8 · Cited by 26
Reproduction and migration in relation to senescence in the barn swallow Hirundo rustica: A study of avian ‘centenarians’
Møller, A. P., de Lope, F., & Saino, N. (2005) · AGE · doi:10.1007/s11357-005-4557-7 · Cited by 26
“While retrospective comparisons of the phenotypes of extremely old individuals with matched controls that fail to reach advanced ages is a standard technique in gerontology (Miller 1966), such comparisons have to the best of our knowledge never been done on animal populations in nature.”
Background
Enhanced immune responses and resistance against infection in aged mice conferred by Flu-ISCOMs vaccine correlate with up-regulation of costimulatory molecule CD86
Sambhara, S. R. (1998) · Vaccine · doi:10.1016/s0264-410x(98)00130-3 · Cited by 26
Robustness Into Advanced Age of Atopy-Specific Mechanisms in Atopy-Prone Families
Jackola, D. R., Pierson-Mullany, L. K., Daniels, L. R., Corazalla, E. O., Rosenberg, A., & Blumenthal, M. N. (2003) · The Journals of Gerontology Series A · doi:10.1093/gerona/58.2.b99 · Cited by 26
Soluble Receptor Activator of Nuclear Factor-κB Ligand (sRANKL)/Osteoprotegerin Balance in Ageing and Age-Associated Diseases
Pulsatelli, L., Dolzani, P., Silvestri, T., Caraceni, P., Facchini, A., Ravaglia, G., Salvarani, C., Melicòni, R., & Mariani, E. (2004) · Biogerontology · doi:10.1023/b:bgen.0000025075.04136.ec · Cited by 26
“Age-related modifications of immune functions have been extensively reported and are thought to contribute to the enhanced susceptibility to infections and neoplastic diseases observed in old subjects (Miller 1996; Pawelec et al. 2002).”
Background
Novel Soybean Oils Differing in Fatty Acid Composition Alter Immune Functions of Moderately Hypercholesterolemic Older Adults3
Han, S. N., Lichtenstein, A. H., Ausman, L. M., & Meydani, S. N. (2012) · Journal of Nutrition · doi:10.3945/jn.112.164335 · Cited by 25
“Inflammatory and T cell-mediated responses are dysregulated in older adults (9).”
Background
Effects of transportation, relocation, and acclimation on phenotypes and functional characteristics of peripheral blood lymphocytes in rhesus monkeys (Macaca mulatta)
Nehete, P. N., Shelton, K. A., Nehete, B. P., Chitta, S., Williams, L. E., Schapiro, S. J., & Abee, C. R. (2017) · PLoS ONE · doi:10.1371/journal.pone.0188694 · Cited by 25
Impact of age on CD4 recovery and viral suppression over time among adults living with HIV who initiated antiretroviral therapy in the African Cohort Study
the AFRICOS Study Group, Bahemana, E., Esber, A. L., Dear, N. F., Ganesan, K., Parikh, A. P., Reed, D. M., Maganga, L., Khamadi, S. A., Mizinduko, M. M., et al. (2020) · AIDS Research and Therapy · doi:10.1186/s12981-020-00323-x · Cited by 28
Impaired GATA3-Dependent Chromatin Remodeling and Th2 Cell Differentiation Leading to Attenuated Allergic Airway Inflammation in Aging Mice
Hasegawa, A., Miki, T., Hosokawa, H., Hossain, M. B., Shimizu, C., Hashimoto, K., Kimura, M. Y., Yamashita, M., & Nakayama, T. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.4.2546 · Cited by 25
“These results suggest that CD4 T cells from aging mice have a moderately decreased proliferative response to anti-TCR stimulation, a finding consistent with previous reports (17, 18).”
Result
Spleen Cells from Young but Not Old Immunized Mice Eradicate Large Established Cancers
Schreiber, K., Arina, A., Engels, B., Spiotto, M. T., Sidney, J., Sette, A., Karrison, T. G., Weichselbaum, R. R., Rowley, D. A., & Schreiber, H. W. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-0127 · Cited by 25
“The age of the individual at the moment of immunization is known to be critical for effective vaccination (30).”
Background
Glycerol-3-phosphate acyltransferase-1 regulates murine T-lymphocyte proliferation and cytokine production
Collison, L. W., Murphy, E. J., & Jolly, C. A. (2008) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00371.2007 · Cited by 25
Risk factors for 28-day mortality in elderly patients with extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia
Ku, N. S., Kim, Y. C., Kim, M. H., Song, J. E., Oh, D. H., Ahn, J. Y., Kim, S. B., Kim, H.-W., Jeong, S. J., Han, S. H., et al. (2013) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2013.07.002 · Cited by 25
“Older patients are nutritionally or immunologically impaired, making them an easy target for infection and its associated complications (Miller, 1996).”
Background
Age and menopause affect the expression of specific cytokines/chemokines in plasma and cervical lavage samples from female sex workers in Nairobi, Kenya
Sivro, A., Lajoie, J., Kimani, J., Jaoko, W. G., Plummer, F. A., Fowke, K. R., & Ball, T. B. (2013) · Immunity & Ageing · doi:10.1186/1742-4933-10-42 · Cited by 26
“In fact, aging has been associated with decrease in lymphocyte proliferative responses, reduced delayed type hypersensitivity reactions and decreased antibody responses to vaccination and infection [9-11].”
Background
Serum immunoglobulin G levels in very old common terns Sterna hirundo
Apanius, V., & Nisbet, I. C. T. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(03)00105-0 · Cited by 25
EFFECTS OF HEAVY METALS ON IMMUNOCOMPETENCE OF WHITE-FOOTED MICE (PEROMYSCUS LEUCOPUS)
Biser, J. A., Vogel, L. A., Berger, J., Hjelle, B. L., & Loew, S. S. (2004) · Journal of Wildlife Diseases · doi:10.7589/0090-3558-40.2.173 · Cited by 25
Vitamin and Micronutrient Intake and the Risk of Community-Acquired Pneumonia in US Women
Neuman, M. I., Willett, W. C., & Curhan, G. C. (2007) · The American Journal of Medicine · doi:10.1016/j.amjmed.2006.06.045 · Cited by 25
Effect of Lactobacillus paracasei NCC2461 on Antigen-Specific T-Cell Mediated Immune Responses in Aged Mice
Vidal, K., Benyacoub, J., Moser, M., Sanchez-Garcia, J., Serrant, P., Segura-Roggero, I., Reuteler, G., & Blum, S. (2008) · Rejuvenation Research · doi:10.1089/rej.2008.0780 · Cited by 25
Age-related changes in interferon-α/β receptor expression, binding, and induction of apoptosis in natural killer cells from C57BL/6 mice
Plett, P. A., Gardner, E. M., & Murasko, D. M. (2000) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(00)00164-0 · Cited by 25
Chronic resveratrol intake reverses pro-inflammatory cytokine profile and oxidative DNA damage in ageing hybrid mice
Wong, Y. T., Gruber, J., Jenner, A. M., Tay, F. E. H., & Ruan, R. (2010) · AGE · doi:10.1007/s11357-010-9174-4 · Cited by 25
“Retardation or reversal of some of the changes associated with immunosenescence in rodents provides the basis for the hypothesis that improvement of the immune function by diet intervention can contribute to better health and extended lifespan (Miller 1996; Walford 1982).”
Background
Influence of Breast Cancer on Thymic Function in Mice
Lopez, D. M., Charyulu, V., & Adkins, B. (2002) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1023/a:1020356020542 · Cited by 25
“Thymic involution occurs in several physiological and pathological conditions, such as aging ( 29 ), graft versus host disease (30), and some infectious diseases, e.g., AIDS (31).”
Background
Aging, Nutritional Status, and Infection in the Developing World
Meydani, A., Ahmed, T., & Meydani, S. N. (2005) · Nutrition Reviews · doi:10.1111/j.1753-4887.2005.tb00379.x · Cited by 25
Age-dependent remodeling of peripheral blood CD4+ CD8+ T lymphocytes in cynomolgus monkeys
Nam, K., Akari, H., Terao, K., Ohto, H., ITAGAKI, S.-I., & Yoshikawa, Y. (1998) · Developmental & Comparative Immunology · doi:10.1016/s0145-305x(97)00058-x · Cited by 25
Activated T Lymphocytes Disappear from Circulation during Endotoxemia in Humans
Krabbe, K. S., Brüünsgaard, H., Qvist, J., Fonsmark, L., Møller, K., Hansen, C. M., Skinhøj, P., & Pedersen, B. K. (2002) · Clinical and Vaccine Immunology · doi:10.1128/cdli.9.3.731-735.2002 · Cited by 25
“Aging is also characterized by an increased number of circulating memory cells, a decreased number of naïve cells (5, 12, 16), down regulation of CD28 (3, 4), and an increased expression of CD95 within both CD4 and CD8 cells.”
Background
Activation of NK1.1+T Cellsin Vitroand Their Possible Role in Age-Associated Changes in Inducible IL-4 Production
Poynter, M. E., Mu, H., Chen, X., & Daynes, R. A. (1997) · Cellular Immunology · doi:10.1006/cimm.1997.1141 · Cited by 25
HORMONAL AND IMMUNOLOGIC RISK FACTORS FOR THE DEVELOPMENT OF RHEUMATOID ARTHRITIS: AN INTEGRATIVE PHYSIOPATHOGENETIC PERSPECTIVE
Masi, A. T. (2000) · Rheumatic Disease Clinics of North America · doi:10.1016/s0889-857x(05)70169-1 · Cited by 25
Repertoire of Antibody Response in Bone Marrow and the Memory Response Are Differentially Affected in Aging Mice
Lu, Y.-F., & Černý, J. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.9.4920 · Cited by 25
Social environment improves immune function and redox state in several organs from prematurely aging female mice and increases their lifespan
Garrido, A., Cruces, J., Ceprián, N., Corpas, I., Tresguerres, J. A. F., & la Fuente, M. D. (2018) · Biogerontology · doi:10.1007/s10522-018-9774-4 · Cited by 26
“…the maintenance of these lymphoproliferative responses has been described as predictive of low morbidity andmortality (Arranz et al. 2010b;Martı́nez de Toda et al. 2017) due to T-cells being considered extremely sensitive to immunosenescence (Miller 1996; Castle 2000; Pawelec et al. 2002).”
Background
Gene-edited healthy donor CAR T cells show superior anti-tumour activity compared to CAR T cells derived from patients with lymphoma in an in vivo model of high-grade lymphoma
Graham, C., Jóźwik, A., Quartey‐Papafio, R., Ioannou, N., Metelo, A. M., Scala, C., Dickson, G. J., Stewart, O., Almena-Carrasco, M., Peranzoni, E., et al. (2021) · Leukemia · doi:10.1038/s41375-021-01324-z · Cited by 25
Attenuated phagocytosis of secondary necrotic neutrophils by macrophages in aged and SMP30 knockout mice
Takahashi, R., Totsuka, S., Ishigami, A., Kobayashi, Y., & Nagata, K. (2015) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/ggi.12436 · Cited by 24
Age-related changes in cell surface and senescence markers in the spleen of DBA/2 mice: A flow cytometric analysis
Connoy, A., Trader, M., & High, K. P. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.11.003 · Cited by 24
Radioligand-Binding Assay Reveals Distinct Autoantibody Preferences for Type I Interferons in APS I and Myasthenia Gravis Subgroups
Hapnes, L., Willcox, N., Oftedal, B. E., Owe, J. F., Gilhus, N. E., Meager, A., Husebye, E. S., & Wolff, A. S. B. (2011) · Journal of Clinical Immunology · doi:10.1007/s10875-011-9617-4 · Cited by 24
“These might reflect: (a) pre-neoplastic changes in thymic remnants analogous to those in a mouse model of small cell lung cancer [34], or even an occult or recently rejected thymoma; (b) the generally higher prevalences of many autoAbs in elderly subjects [35–37], though that was not evident in the type I IFN autoAbs…”
Result
INFLUENCE OF SEX AND AGE ON MORPHOLOGICAL ORGAN DAMAGE AFTER HEMORRHAGIC SHOCK
Mees, S. T., Gwinner, M., Marx, K., Faendrich, F., Schroeder, J., Haier, J., & Kahlke, V. (2008) · Shock · doi:10.1097/shk.0b013e31815c3ea0 · Cited by 24
“Furthermore, ageing is associated with impaired immune functions, leading to a higher incidence of bacterial sepsis, increased LPS sensitivity, and mortality in sepsis (6).”
Background
Molecular and Cellular Aspects of Macrophage Aging
Sebastián, C., Lloberas, J., & Celada, A. (2009) · Springer eBooks · doi:10.1007/978-1-4020-9063-9_46 · Cited by 24
Do thymically and strictly extrathymically developing T cells generate similar immune responses?
Blais, M., Gérard, G., Martinic, M. M. A., Roy-Proulx, G., Zinkernagel, R. M., & Perreault, C. (2003) · Blood · doi:10.1182/blood-2003-09-3311 · Cited by 24
Macroprolactinemia: The Consequences of a Laboratory Pitfall
Toldy, E., Lőcsei, Z., Szabolcs, I., Góth, M., Kneffel, P., Szőke, D., & Kovács, G. L. (2003) · Endocrine · doi:10.1385/endo:22:3:267 · Cited by 24

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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