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THE IMMUNOLOGIC THEORY OF AGING
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“The age-related involvement of immune system leads to a progressive reduction in the ability to trigger effective antibody and cellular responses against infections and vaccinations.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [4]
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Aiello, A., Farzaneh, F., Candore, G., Caruso, C., Davinelli, S., Gambino, C. M., Ligotti, M. E., Zareian, N., & Accardi, G. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02247 · Cited by 693
Role of Free Radicals in Aging and Disease
Harman, D. (1992) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1992.tb27444.x · Cited by 265
Harman, D. (1994) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1994.tb12069.x · Cited by 270
Targeting immune dysfunction in aging
Borgoni, S., Kudryashova, K. S., Burka, K., & de Magalhães, J. P. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101410 · Cited by 232
PROTEIN SYNTHESIS AND DEGRADATION DURING AGING AND SENESCENCE
Makrides, S. C. (1983) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/j.1469-185x.1983.tb00394.x · Cited by 179
Microglia regulation of central nervous system myelin health and regeneration
Kent, S. A., & Miron, V. E. (2024) · Nature Reviews Immunology · doi:10.1038/s41577-023-00907-4 · Cited by 183
“This senescent cell accumulation is thought to occur as a result of immunosenescence — the gradual decline in immune function as an organism ages 206 — whereby decreased immune function results in reduced capacity to clear senescent cells efficiently 140 .”
THE EXPERIMENTAL MANIPULATION OF AGEING BY DIET
Holehan, A. M., & Merry, B. J. (1986) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/j.1469-185x.1986.tb00658.x · Cited by 154
Harman, D. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb09886.x · Cited by 153
Lymphocytes, Hormones and Ageing
Fabris, Ν., Pierpaoli, W., & Sorkin, E. (1972) · Nature · doi:10.1038/240557a0 · Cited by 148
Goldstein, S. (1971) · New England Journal of Medicine · doi:10.1056/nejm197111112852005 · Cited by 127
Influence of the main histocompatibility complex on ageing in mice
Smith, G. S., & Walford, R. L. (1977) · Nature · doi:10.1038/270727a0 · Cited by 121
Self-citationMusella, A., Gentile, A., Rizzo, F. R., Vito, F. D., Fresegna, D., Bullitta, S., Vanni, V., Guadalupi, L., Bassi, M. S., Buttari, F., et al. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00238 · Cited by 126
“On the other hand, advanced age is associated with a phenomenon called immunosenescence (ISC) which refers to a weakening in integrity and efficiency of the adaptive and innate immune systems (Walford, 1969; Denkinger et al., 2015; Di Benedetto et al., 2017).”
BackgroundAcute Childhood Leukaemia in Relation to the HL–A Human Transplantation Genes
Walford, R. L., Finkelstein, S., Neerhout, R., et al. (1970) · Nature · doi:10.1038/225461a0 · Cited by 109
Self-citationNatural Autoantibodies Constitute a Substantial Part of Normal Circulating Immunoglobulins
Dighiero, G., Lymberi, P., Guilbert, B., Ternynck, T., & Avraméas, S. (1986) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1986.tb20863.x · Cited by 105
Boche, D., & Nicoll, J. A. R. (2008) · Brain Pathology · doi:10.1111/j.1750-3639.2008.00134.x · Cited by 106
“This led to two different hypotheses: (i) auto-antibodies contribute to the diseases associated with ageing, as occurs in autoimmune disease (116); or (ii) auto-antibodies play a role in eliminating senescent cells to maintain the integrity of the host (37).”
BackgroundSurvival and disease patterns in C57BL/6J mice subjected to undernutrition
Cheney, K. E., Liu, R. K., Smith, G. S., Leung, R. E., Mickey, M. R., & Walford, R. L. (1980) · Experimental Gerontology · doi:10.1016/0531-5565(80)90029-7 · Cited by 91
Self-citationThe measurement of biological age
Ludwig, F. C., & Smoke, M. E. (1980) · Experimental Aging Research · doi:10.1080/03610738008258384 · Cited by 85
Sex/gender-related differences in inflammaging
Olivieri, F., Marchegiani, F., Matacchione, G., Giuliani, A., Ramini, D., Fazioli, F., Sabbatinelli, J., & Bonafè, M. (2023) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2023.111792 · Cited by 89
“When people age, the capacity of their immune system for immunosurveillance gradually declines, a phenomenon called immunosenescence (Walford, 1969).”
Duffy, P. H., Feuers, R. J., & Hart, R. W. (1990) · Chronobiology International · doi:10.1080/07420529009064635 · Cited by 81
Greeley, E. H., Ballam, J. M., Harrison, J., Kealy, R. D., Lawler, D. F., & Segre, M. (2001) · Veterinary Immunology and Immunopathology · doi:10.1016/s0165-2427(01)00336-1 · Cited by 79
Bellinger, D. L., Felten, S. Y., Collier, T. J., & Felten, D. L. (1987) · Journal of Neuroscience Research · doi:10.1002/jnr.490180110 · Cited by 77
The Senescence of the Immune System
Weksler, M. E. (1981) · Hospital Practice · doi:10.1080/21548331.1981.11946847 · Cited by 76
Crews, D. E. (2003) · Cambridge University Press eBooks · doi:10.1017/cbo9780511542350 · Cited by 69
Human senescence evolutionary and biocultural perspectives
Crews, D. E. (2003) · Cited by 67
The Problem of Theory in Gerontology Today
Bengtson, V. L., Putney, N. M., & Johnson, M. (2005) · Cambridge University Press eBooks · doi:10.1017/cbo9780511610714.003 · Cited by 63
“A second neuroendocrine explanation, the immunological theory of ageing (Walford, 1969), is based on the observation that the functional capacity and fidelity of the immune system declines with age, as indicated by the strong age-associated increase in autoimmune disease.”
BackgroundThe immune system, amyloid‐β peptide, and Alzheimer's disease
Weksler, M. E., Gouras, G. K., Relkin, N. R., & Szabo, P. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00264.x · Cited by 60
“Walford (9) proposed an Immunological Theory of Aging that saw autoantibodies contributing importantly to the diseases of aging, as they did to the pathogenesis of autoimmune diseases.”
BackgroundSelf‐Tolerance Maintained by Active Suppressor Mechanisms
Cunningham, A. J. (1976) · Immunological Reviews · doi:10.1111/j.1600-065x.1976.tb01451.x · Cited by 59
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Role of cytokines and reactive oxygen species in brain aging
MohanKumar, S. M. J., Murugan, A., Palaniyappan, A., & MohanKumar, P. S. (2023) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2023.111855 · Cited by 59
Fever and sickness behaviour vary among congeneric rodents
Martin, L. B., Weil, Z. M., & Nelson, R. J. (2007) · Functional Ecology · doi:10.1111/j.1365-2435.2007.01347.x · Cited by 57
“Perhaps more modest APRs in some species exist to promote survival through decreased oxidative damage (Walford 1969; Sohnle & Gambert 1982; Finch & Crimmins 2004), as these species are protected against infection by other types of potentially less self-damaging immune defences (Martin et al.”
BackgroundMasoro, E. J. (1994) · Comprehensive physiology · doi:10.1002/j.2040-4603.1994.tb01673.x · Cited by 56
“A similar line of reasoning led Walford (130) to link age changes in the immune system to organismic aging in general.”
An immunologist’s guide to immunosenescence and its treatment
Caruso, C., Ligotti, M. E., Accardi, G., Aiello, A., & Candore, G. (2022) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2022.2106217 · Cited by 53
“described in his famous book ‘The immunologic theory of aging’ [6], Walford assumed that immune-mediated tissue damage is caused by organismal aging, even though he did not discuss the alterations in immunity itself.”
BackgroundThe prevalence of autoantibodies in an elderly sub-Saharan African population
Njemini, R., Meyers, I., Demanet, C., et al. (2002) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.2002.01713.x · Cited by 51
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“The decline with age in normal immune functions is generally associated with an increase in the frequency of autoimmune and immune complex diseases, cancer, and viral and fungal infections (1-3).”
BackgroundAbraham, C., Tal, Y., & Gershon, H. E. (1977) · European Journal of Immunology · doi:10.1002/eji.1830070512 · Cited by 51
Is the Phenotypic Combination A1B8Cw7DR3 a Marker for Male Longevity?
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“21 The summary meta-analysis used Woolf's method with the Mantel Haenszel heterogeneity Chi-squared STATISTICAL ANALYSIS (Het Chi) to assess variability between series.(2) 1 The standard Chi-squared analysis with Mantel Haenszel or Yates' P value, P < 0.”
MethodImmune surveillance of senescence: potential application to age-related diseases
Wang, T., & Nakanishi, M. (2024) · Trends in Cell Biology · doi:10.1016/j.tcb.2024.06.007 · Cited by 49
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Relation between exploratory activity and immune function in aged mice: a preliminary study
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Natural Autoantibodies, Tolerance, and Autoimmunity
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Psychoimmunologic and Endorphin Function in the Ageda
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Genetics of Anti‐A and Anti‐B Levels
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Self-citationAging-associated dysregulation of homeostatic immune response termination (and not initiation)
Pattabiraman, G., Palasiewicz, K., Galvin, J. P., & Ucker, D. S. (2017) · Aging Cell · doi:10.1111/acel.12589 · Cited by 29
“Certainly, the aging-associated elevation of levels of circulating autoantibodies [rheumatoid factors, including antinuclear antibodies (Walford, 1969)], especially contemporaneous with a waning of antigen-specific responsiveness represents a confounding complexity.”
BackgroundBullough, W. S. (1971) · Nature · doi:10.1038/229608a0 · Cited by 29
A Neuroendocrine-Immune Theory of Aging
Fabris, N. (1990) · International Journal of Neuroscience · doi:10.3109/00207459008999749 · Cited by 28
Manini, T. M., Anton, S. D., Beavers, D. P., Cauley, J. A., Espeland, M. A., Fielding, R. A., Kritchevsky, S. B., Leeuwenburgh, C., Lewis, K. H., Liu, C. K., et al. (2017) · Journal of the American Geriatrics Society · doi:10.1111/jgs.14965 · Cited by 28
“The role of the immune system in the aging process has been actively studied since seminal work in 1969.(1) A large body of evidence demonstrating chronic, low-grade elevation of inflammatory markers with increasing age has since accumulated.”
Microbiome, Immunosenescence, and Chronic Kidney Disease
Stavropoulou, E., Kantartzi, K. M., Tsigalou, C., Aftzoglou, K., Voidarou, C., Konstantinidis, T. G., Chifiriuc, M. C., Thodis, E. D., & Bezirtzoglou, E. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.661203 · Cited by 27
“The term immunosenescence was coined by RoyWalford (84) when he published his hallmark book entitled “The Immunologic Theory of Aging” (85).”
BackgroundAging in Rodents Fed Restricted Diets*,†
Weindruch, R. H. (1985) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1985.tb02278.x · Cited by 26
Biology of the Gene: The Ergon/Chronon System
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HENDERSON AWARD LECTURE: Studies in Immunogerontology*
Walford, R. L. (1982) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1982.tb05057.x · Cited by 25
Self-citationDNA Repair, H‐2, and Aging in NZB and CBA Mice
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Morphometrical Characteristics of Age‐Associated Changes in the Thymus of Old Male Wistar Rats
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“The age-associated thymic involution, a consistent phenomenon in all vertebrate species, has been proposed to be a primary event leading to immunological aging (Walford, 1969).”
BackgroundT cell immunosenescence, hypertension, and arterial stiffness
Yu, H. T., & Shin, E. (2014) · Epidemiology and Health · doi:10.4178/epih/e2014005 · Cited by 22
“functional and phenotypic changes on both cellular and systemic levels [1,2].”
BackgroundAGE‐RELATED CHANGES OF THYMUS – MORPHOLOGICAL and FUNCTIONAL ASPECTS –
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“It also affects both ancestral/innate and acquired/adaptive immunity, although T lymphocytes are dramatically affected [6].”
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thymus, immunity and autoimmunity*
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Enhancement of Lewis lung carcinoma in a syngeneic host by spleen cells of C57BL/6 old mice
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“Some suggest that the link between lower Tb and longer lifespan is due to the suppression of autoimmunity in old age (Walford 1969) or a resistance to a variety of environmental stressors (Rikke and Johnson 2004).”
BackgroundAge-related Changes in the Tiger Salamander Retina
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Metabolic dysregulation of trained immunity in immune aging and the impact of dietary patterns
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Immunosenescence and Inflammaging in Dogs and Cats: A Narrative Review
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Triggering of Toll-like Receptors in Old Individuals. Relevance for Vaccination
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Genetics of Autoantibodies in Relation to Disease
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Historical, Cross‐cultural, Biological and Psychosocial Perspectives of Ageing and the Aged Person
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“The association only appears significant when considering a subset of SNPs in the homologs of VPS70, rather than in a genome-wide analysis.”
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The role of nutrition in aging.
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Aging and chromosomal instability
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Metadata
- Authors
- Walford, R. L.
- Corresponding author
- Walford, Roy L.
- Venue
- Immunological Reviews
- Publisher
- Wiley
- Published
- 1969-09
- Volume
- 2
- Issue
- 1
- Pages
- 171-171
- ISSN
- 0105-2896 (ISSN-L)
- 1600-065X
- OpenAlex
- W2108894325
- Cited by
- 284
- References
- 0
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 5 · 2023: 5 · 2022: 5 · 2021: 11 · 2020: 3 · 2019: 6 · 2018: 5 · 2017: 5 · 2016: 1 · 2015: 2 · 2014: 1 · 2013: 2 · 2012: 1
- FWCI
- 6.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Immunological Reviews (publishedVersion)
- 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
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- aging, immune system, immunosenescence, senescence
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 ›
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