The DOI matches its Crossref record; 126 of the 126 references it cites were found in a registry or an index; none of the 118 sources its claims cite is checked for support yet.
Causes, consequences, and reversal of immune system aging
Open accessAbstract
The effects of aging on the immune system are manifest at multiple levels that include reduced production of B and T cells in bone marrow and thymus and diminished function of mature lymphocytes in secondary lymphoid tissues. As a result, elderly individuals do not respond to immune challenge as robustly as the young. An important goal of aging research is to define the cellular changes that occur in the immune system and the molecular events that underlie them. Considerable progress has been made in this regard, and this information has provided the rationale for clinical trials to rejuvenate the aging immune system.
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76 Not checked yet · 14 Own interpretation · 10 No basis given
In the paper
“Despite the increase in their number, myeloid-biased stem cells are not as robust as their young counterparts (24)”
§ Causes, consequences, and reversal of immune system aging > Effects of aging on immune system development
What the sources say
- Not checked yetcites [24] source
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In the paper
“This is illustrated by increased vulnerability of individuals 70 years of age and older to influenza (1)”
§ Causes, consequences, and reversal of immune system aging > Introduction
What the sources say
- Not checked yetcites [1] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“As a result, elderly individuals do not respond to immune challenge as robustly as the young.”
- Also stated in: § Introduction · hedged
“While elderly individuals are by no means immunodeficient, they often do not respond efficiently to novel or previously encountered antigens.”
- Also stated in: § Introduction · plain
“This is illustrated by increased vulnerability of individuals 70 years of age and older to influenza (1), a situation that is exacerbated by their poor response to vaccination (2)(3)(4).”
§ Causes, consequences, and reversal of immune system aging > Abstract
What the sources say
- Not checked yetcites [1] source
- Not checked yetcites (2)(3)(4)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Introduction · hedged
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In the paper
“which in turn could underlie the numerous age-related deficiencies observed in mature myeloid cells such as neutrophils and macrophages (25,26).”
§ Causes, consequences, and reversal of immune system aging > Effects of aging on immune system development
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In the paper
“This shift has been correlated with increased expression of myeloid lineage genes and downregulation of those specifying a lymphoid lineage fate (11,17).”
§ Causes, consequences, and reversal of immune system aging > Effects of aging on immune system development
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In the paper
“primary lymphopoiesis in the elderly is significantly diminished, as exemplified by involution of the thymus (8)(9)(10).”
§ Causes, consequences, and reversal of immune system aging > Effects of aging on immune system development
What the sources say
- Not checked yetcites (8)(9)(10)
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The causes of this age-related reduction in lymphocyte development are multifactorial and include changes in HSCs and progenitor cells (11,12) as well as the local tissue and systemic environments (13,14).”
§ Causes, consequences, and reversal of immune system aging > Effects of aging on immune system development
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The age-related increase in expression of myeloid lineage genes in the studies noted above (11,17) likely resulted from the accumulation of myeloid-biased HSCs, as these analyses were performed on unseparated pools of HSCs.”
§ Causes, consequences, and reversal of immune system aging > Effects of aging on immune system development
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“a situation that is exacerbated by their poor response to vaccination (2)(3)(4).”
§ Causes, consequences, and reversal of immune system aging > Introduction
What the sources say
- Not checked yetcites (2)(3)(4)
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“this has led to the conclusion that age-related changes in the endocrine system contribute to declines in lymphopoiesis.”
§ Causes, consequences, and reversal of immune system aging > Effects of aging on immune system development
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 28
- Probably not a substantial claim. 3
None of the sources cited for this claim have been checked yet.
In the paper
“From an immunologic perspective, the most profound effect of stem cell aging in both mice (11,18) and humans (17) is a decreased capacity to produce lymphocytes and an increase in myeloid potential.”
§ Causes, consequences, and reversal of immune system aging > Effects of aging on immune system development
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“it is now appreciated that the number of lymphoid-biased stem cells declines with age concomitant with an increase in myeloid-biased HSCs (19).”
§ Causes, consequences, and reversal of immune system aging > Effects of aging on immune system development
What the sources say
- Not checked yetcites [19] source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The effects of aging on the immune system are manifest at multiple levels that include reduced production of B and T cells in bone marrow and thymus and diminished function of mature lymphocytes in secondary lymphoid tissues.”
- Also stated in: § Effects of aging on immune system development · plain
“primary lymphopoiesis in the elderly is significantly diminished, as exemplified by involution of the thymus (8)(9)(10).”
- Also stated in: § Effects of aging on immune system development · plain
“the number of B cell (28)(29)(30)(31) and T cell (32,33) progenitors in bone marrow and thymus is markedly reduced with age.”
§ Causes, consequences, and reversal of immune system aging > Abstract
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Also stated in: § Effects of aging on immune system development · plain
None of the sources cited for this claim have been checked yet.
In the paper
“HSCs exhibit multiple age-related changes that include impaired adherence to stromal cells and, in some strains of mice (15,16) and elderly humans (17), an increase in number.”
§ Causes, consequences, and reversal of immune system aging > Effects of aging on immune system development
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The effects of aging on the immune system are widespread and affect the rate at which naive B and T cells are produced as well as the composition and quality of the mature lymphocyte pool.”
- Also stated in: § Aging and the decline of immune function · boosted
“The answer is that the composition and quality of the mature lymphocyte pool is profoundly altered by aging.”
§ Causes, consequences, and reversal of immune system aging > Introduction
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Aging and the decline of immune function · boosted
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“However, chronic stimulation with persistent viral infections such as CMV can exhaust the naive pool of cells and result in an oligoclonal memory cell expansion.”
§ Causes, consequences, and reversal of immune system aging > Aging and the decline of immune function
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“This decline is likely due to decreased numbers of IgM + memory and switched memory B cells, because the total number of naive B cells remains unchanged by aging (51,52).”
§ Causes, consequences, and reversal of immune system aging > Figure 1
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Regardless of how the shift occurs from a salutary to an inflammatory milieu, the end result may be a negative effect on the ability of naive lymphocytes from the bone marrow or thymus to lodge in an organ such as the spleen as well as the function of mature lymphocytes already resident in that tissue.”
§ Causes, consequences, and reversal of immune system aging > Figure 1
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Similar to B cell progenitors, ETPs and DN cells from old mice also exhibit age-related defects in proliferation and high rates of apoptosis (ref.32 and Figure 1).”
§ Causes, consequences, and reversal of immune system aging > Effects of aging on immune system development
What the sources say
- Not checked yetcites (ref.32)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“These oligoclonal expanded CD8 + memory T cells are further distinguished in humans by loss of expression of the CD28 co-stimulatory molecule (47,48) and impaired immune function.”
§ Causes, consequences, and reversal of immune system aging > Figure 1
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The accumulation of CD8 + CD28 -T cells and CMV seropositivity are components of the immune risk profile, which has been proposed as a predictor of mortality in individuals 65 and older (49)”
§ Causes, consequences, and reversal of immune system aging > Figure 1
What the sources say
- Not checked yetcites [49] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Lymphoid-biased HSCs in old mice also appear to accumulate deficiencies that, as discussed below, may compromise their selfrenewal potential and contribute to the decline of this population (27).”
§ Causes, consequences, and reversal of immune system aging > Effects of aging on immune system development
What the sources say
- Not checked yetcites [27] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Age-relat-ed microenvironmental changes also have a major impact in the thymus, where T cell development is dependent upon an intact thymic milieu composed of fibroblasts, macrophages, dendritic cells, and thymic epithelial cells.”
§ Causes, consequences, and reversal of immune system aging > Effects of aging on immune system development
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“B cell number in mice is unchanged by aging, but in human peripheral blood their absolute number is reduced (51).”
§ Causes, consequences, and reversal of immune system aging > Figure 1
What the sources say
- Not checked yetcites [51] source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“It is clear that the number of thymic epithelial cells declines over time and that they are not replaced, as a result of impaired proliferation (38).”
§ Causes, consequences, and reversal of immune system aging > Effects of aging on immune system development
What the sources say
- Not checked yetcites [38] source
boosteddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“For example, common lymphoid progenitors, pre-pro-B cells, and pro-B cells from old mice do not proliferate as extensively as do young cells, and they exhibit significantly higher rates of apoptosis.”
§ Causes, consequences, and reversal of immune system aging > Effects of aging on immune system development
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Levels of ROS in cells may also be regulated by ataxia telangiectasia mutated (ATM) kinase, and age-related declines in expression of ATM can result in an increase in ROS in cells (77,78).”
§ Causes, consequences, and reversal of immune system aging > Intracellular changes in developing and mature lymphocytes
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“CD4 + T cells exhibit reduced T cell receptor signaling intensity and altered production of various cytokines following antigen binding (70,71).”
§ Causes, consequences, and reversal of immune system aging > Figure 1
What the sources say
- Not checked yetcites [70] Maue, 2009, Curr Opin Immunol.
- Not checked yetcites [71] source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, repeated cell division may result in progressive telomere shortening that in turn results in DNA damage that can no longer be repaired efficiently due to agerelated defects in DNA repair mechanisms (75).”
§ Causes, consequences, and reversal of immune system aging > Intracellular changes in developing and mature lymphocytes
What the sources say
- Not checked yetcites [75] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“GH and IGF-1 bind to receptors expressed on thymocytes (101) and thymic epithelial cells (102)”
§ Causes, consequences, and reversal of immune system aging > Rejuvenating the aging immune system
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“mice with hypomorphic expression of DNMT1 exhibit relatively normal myeloerythroid potential but show a significant block in lymphoid development (92).”
§ Causes, consequences, and reversal of immune system aging > Intracellular changes in developing and mature lymphocytes
What the sources say
- Not checked yetcites [92] source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“In this regard, loss of DNMT3a impairs differentiation of HSCs while their number increases in the bone marrow (91)”
§ Causes, consequences, and reversal of immune system aging > Intracellular changes in developing and mature lymphocytes
What the sources say
- Not checked yetcites [91] source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Wang and colleagues demonstrated that BATF levels increased in HSCs in response to DNA damage and that this resulted in the differentiation of lymphoid-biased HSCs at the expense of their self-renewal (27).”
§ Causes, consequences, and reversal of immune system aging > Intracellular changes in developing and mature lymphocytes
What the sources say
- Not checked yetcites [27] source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“recent studies have shown that both Ink4a and Arf expression increases in pro-B cells from old mice and that inhibiting their expression can partially reverse the effects of aging (81).”
§ Causes, consequences, and reversal of immune system aging > Intracellular changes in developing and mature lymphocytes
What the sources say
- Not checked yetcites [81] source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“GH treatment resulted in increased thymic mass, increased thymic output as measured by T cell receptor rearrangement excision circles in circulating T cells, and increased numbers of naive CD4 + T cells.”
- Also stated in: § Rejuvenating the aging immune system · plain
“It is important to note that the effects of GH were not thymus specific, as the subjects also had expanded numbers of naive peripheral CD4 + T cells (105).”
§ Causes, consequences, and reversal of immune system aging > Rejuvenating the aging immune system
What the sources say
- Not checked yetcites [105] Napolitano, 2008, J Clin Invest.
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Also stated in: § Rejuvenating the aging immune system · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and suggest that such interventions could be administered to a large cohort of individuals.”
§ Causes, consequences, and reversal of immune system aging > Caveats in immune system rejuvenation
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“it is not unreasonable to expect that this information will continue to be translated into therapies to rejuvenate the aging immune system.”
§ Causes, consequences, and reversal of immune system aging > Conclusions and perspectives
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
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Probably not a substantial claim. It may be too vague to check against evidence.
In the paper
“As predicted, levels of Ink4a expression in ETPs and DN cells harvested from FGF7-treated mice were downregulated, and these cells exhibited enhanced proliferation (82).”
§ Causes, consequences, and reversal of immune system aging > Rejuvenating the aging immune system
What the sources say
- Not checked yetcites [82] source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“a tremendous amount is now known regarding the cellular changes that occur in the aging immune system and the molecular events that underlie them.”
§ Causes, consequences, and reversal of immune system aging > Conclusions and perspectives
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim. It may be too vague to check against evidence.
In the paper
“beneficial effects were observed when it commenced in adults but were not evident when initiated in prepubertal or aged non-human primates (112).”
§ Causes, consequences, and reversal of immune system aging > Rejuvenating the aging immune system
What the sources say
- Not checked yetcites [112] source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“FGF7 is particularly remarkable because its administration to old mice results in a renewal of the thymic microenvironment, increased numbers of ETPs, and a restoration of thymus cellularity to levels observed in the young (106, 107).”
§ Causes, consequences, and reversal of immune system aging > Rejuvenating the aging immune system
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper relies on this without support.
The thymic effects of GH, IGF-1, and FGF7 are short-lived, and the thymus returns to its previous size after treatment ends.
“because their effects are transient and the thymus reverts to its former size following the cessation of treatment.”
The paper relies on this without support.
Aging affects the immune system differently across individuals.
“It is likely that the effects of aging on the immune system will not be uniform between individuals.”
The paper relies on this without support.
GH, IGF-1, and FGF7 act throughout the body because their receptors are present on cells in many tissues.
“factors such as GH, IGF-1, and FGF7 have widespread systemic effects due to the expression of their receptors on cells in multiple tissues.”
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?
In the citing paper
“Evidence of waning adaptive immunity is already apparent in mid adulthood, as early as at the age of 50 years, with increasing clinical relevance in the 7th–10th decade of life”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Montecino-Rodriguez et al., 2013
In the citing paper
“most older people over the age of 60–65 years (although not all) experience some immune dysregulation that makes them less able to respond to immune challenges [33,34].”
From Immune function and micronutrient requirements change over the life course (2018) · cites this paper as [34]
Citations
Cites
The senescence-associated secretory phenotype: the dark side of tumor suppression
Coppé, J.-P., Desprez, P.-Y., Krtolica, A., & Campisi, J. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102144 · Cited by 5,206
Mortality Associated With Influenza and Respiratory Syncytial Virus in the United States
Thompson, W. W., Shay, D. K., Weintraub, E., Brammer, L., Cox, N., Anderson, L. J., & Fukuda, K. (2003) · JAMA · doi:10.1001/jama.289.2.179 · Cited by 3,673
Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion
Rodier, F., Coppé, J.-P., Patil, C. K., Hoeijmakers, W. A. M., Muñoz, D. P., Raza, S. R., Freund, A., Campeau, E., Davalos, A. R., & Campisi, J. (2009) · Nature Cell Biology · doi:10.1038/ncb1909 · Cited by 2,232
Franceschi, C., Capri, M., Monti, D., Giunta, S., Olivieri, F., Sevini, F., Panourgia, M. P., Invidia, L., Celani, L., Scurti, M., et al. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.016 · Cited by 2,087
Insulin and insulin-like growth factor signalling in neoplasia
Pollak, M. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2536 · Cited by 2,059
Ink4a/Arf expression is a biomarker of aging
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Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19
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“Given the results here, it is tempting to speculate that an already restricted immune response in the aging population prevents successful inhibition of viral spread at early stages of infection, further exacerbating the morbidity and mortality observed for this age group (Jing et al., 2009; Montecino-Rodriguez et al.…”
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The senescence-associated secretory phenotype and its physiological and pathological implications
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“185,186), implies increased vulnerability to developing diseases such as osteoarthritis 187 , rheumatoid arthritis and cardiovascular diseases 188 .”
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“Advanced age is a dominant risk factor for severe COVID-19 and is correlated with reduced immune function (20).”
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Immune function and micronutrient requirements change over the life course
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“ibrutinib, which is indicated in younger patients, from its adverse effect when combined with R-CHOP in older patients; this may be attributable to multiple factors, including impaired immune responses leading to increased infections.(25) Additionally, DLBCL subtype analysis, determined by immunohistochemistry at cent…”
BackgroundImpaired immune surveillance accelerates accumulation of senescent cells and aging
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“The elderly, hospitalized population used in our sensitivity cohort could account for the delayed time to positivity seen in our cohort versus the Abbott package insert (17 versus 14 days after symptom onset), as declining immune responses are associated with advanced age (8).”
SIRT1 is downregulated by autophagy in senescence and ageing
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Toll-like receptor 4 (TLR4): new insight immune and aging
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BackgroundThe aging gut microbiome and its impact on host immunity
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“Agerelated changes in the quality and quantity of immune responses lead to a progressive decline in the ability to trigger effective antibody and cellular responses against infections and vaccinations [2, 12].”
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Successful and Maladaptive T Cell Aging
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“Evidence of waning adaptive immunity is already apparent in mid adulthood, as early as at the age of 50 years, with increasing clinical relevance in the 7th–10th decade of life (Goronzy and Weyand, 2013; Montecino-Rodriguez et al., 2013; Pinti et al., 2016).”
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Human Pathophysiological Adaptations to the Space Environment
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“On Earth, aging affects the cardiovascular, musculoskeletal, nervous, gastrointestinal, urinary and neuroendocrine systems (Boss and Seegmiller, 1981), with immune system impairment and an enhanced inflammatory activity (Montecino-Rodriguez et al., 2013).”
BackgroundNaive T Cell Maintenance and Function in Human Aging
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Regulatory T-Cells: Potential Regulator of Tissue Repair and Regeneration
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“Moreover, accumulating evidence has shown that the function of the immune system declines with age (101, 102).”
BackgroundHallmarks of senescence and aging
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Characteristics of Early-Onset vs Late-Onset Colorectal Cancer
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A sestrin-dependent Erk–Jnk–p38 MAPK activation complex inhibits immunity during aging
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Immune cells and inflammation in AKI to CKD progression
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“Low, but chronic, levels of systemic inflammation and the dysregulation of several innate and acquired immune responses are observed with aging (49, 111).”
BackgroundIL-17 and immunologically induced senescence regulate response to injury in osteoarthritis
Faust, H. J., Zhang, H., Han, J., Wolf, M. T., Jeon, O. H., Sadtler, K., Peña, A. N., Chung, L., Maestas, D. R., Tam, A. J., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci134091 · Cited by 260
“The number of immune cells decreases with aging, but inflammation in the body broadly increases (11, 12).”
BackgroundMacrophages in age-related chronic inflammatory diseases
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“In addition to the local environment, systemic changes that occur with aging, such as decreased levels of growth hormone and IGF-1, may also contribute to the decline in lymphopoiesis.(11) Despite the skewing of aged HSCs toward myelopoiesis, however, the basal inflammation seen in older individuals is not associated…”
BackgroundAging Hallmarks and Progression and Age-Related Diseases: A Landscape View of Research Advancement
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Immune aging, dysmetabolism, and inflammation in neurological diseases
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BackgroundA review of probiotic supplementation in healthy adults: helpful or hype?
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The intersection of radiotherapy and immunotherapy: Mechanisms and clinical implications
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IBD across the age spectrum—is it the same disease?
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Depleting myeloid-biased haematopoietic stem cells rejuvenates aged immunity
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“These data revealed large aging-associated changes in T cell subtype composition and activation, which was identical in Apoe / and WT mice (see also Linton and Dorshkind, 2004; Montecino-Rodriguez et al., 2013).”
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“Two of the most prominent characteristics of aging are immunosenescence (deterioration of immune responses) and inflammaging (presence of chronic low grade inflammation) [124, 125].”
BackgroundImpact of Age on Outcomes with Immunotherapy for Patients with Melanoma
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“, association of age and desmoplastic melanoma), which may predict a higher chance of tumor PD-L1 expression, T-cell infiltration, and increased responsiveness to anti–PD-1/PD-L1 therapy [34, 35].”
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“(26) carefully describe the features of aging of the various components of the cellular immune system including HSCs, thymus, and B and T lymphocytes.”
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Aging impairs peritoneal but not bone marrow‐derived macrophage phagocytosis
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“increased susceptibility to infections, decreased vaccine responses and impaired wound healing in the elderly (Linton & Dorshkind, 2004; Gomez et al., 2008; McElhaney & Effros, 2009; Mahbub et al., 2011; Montecino-Rodriguez et al., 2013).”
BackgroundAging, inflammation and cancer
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Immunosenescence, Inflammaging, and Frailty: Role of Myeloid Cells in Age-Related Diseases
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p53 isoforms regulate aging- and tumor-associated replicative senescence in T lymphocytes
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Faces of cellular senescence in skin aging
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Cellular signaling in the aging immune system
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“, T-cell and B-cell function) and excess production of type 2 cytokines [173,174].”
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“Another important point is that the majority of prosthetic joint replacement surgeries are performed in the elderly, a population known to have waning immunity compared with younger patients (52, 53).”
Sobolev, O., Binda, E., O’Farrell, S., Lorenc, A., Pradines, J., Huang, Y., Duffner, J. L., Schulz, R., Cason, J. W., Zambon, M. C. F. A., et al. (2016) · Nature Immunology · doi:10.1038/ni.3328 · Cited by 149
“This study was not designed to explore the well-established compromise in adaptive responses in subjects aged over 70 27,28 .”
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Inflammaging impairs peripheral nerve maintenance and regeneration
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DAMPs, ageing, and cancer: The ‘DAMP Hypothesis’
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Expression of CD39 on activated T cells impairs their survival in older individuals
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“Aging is associated with a decline in immune function, contributing to the increased susceptibility to infectious diseases and higher incidence of malignant disease (Goronzy and Weyand, 2013; Montecino-Rodriguez et al., 2013; Thompson et al., 2003; Weng, 2006).”
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“Because thymus function and output rapidly decrease with age (Montecino-Rodriguez et al. 2013), most of the T cells may have originated decades ago from HSC clones that were active then.”
BackgroundPlasma cells are obligate effectors of enhanced myelopoiesis in aging bone marrow
Pioli, P. D., Casero, D., Montecino-Rodriguez, E., Morrison, S. L., & Dorshkind, K. (2019) · Immunity · doi:10.1016/j.immuni.2019.06.006 · Cited by 131
Self-citationSex Disparities in COVID-19 Severity and Outcome: Are Men Weaker or Women Stronger?
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The neurovascular unit and systemic biology in stroke — implications for translation and treatment
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Asymptomatic SARS-CoV-2 Carriers: A Systematic Review and Meta-Analysis
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“Meanwhile, elderly people with a weakened immune system (77, 78) are less likely to be asymptomatic carriers.”
BackgroundAge-associated changes in human hematopoietic stem cells
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Mouse aging cell atlas analysis reveals global and cell type-specific aging signatures
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COVID-19, Virology and Geroscience: A Perspective
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Antiaging Effect of Metformin on Brain in Naturally Aged and Accelerated Senescence Model of Rat
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“19,20 Inflamma-tion mediated neurodegeneration involves activation of microglia, the brain’s resident immune cells, which produce pro-inflammatory and neurotoxic cytokines, including tumor necrosis factor-alpha (TNF-a ), interleukin-1 b (IL-1 b ), reactive oxygen species (ROS), and nitric oxide (NO),…”
Age-associated alterations in immune function and inflammation
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Brain Ultrastructure: Putting the Pieces Together
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Haematological manifestations of COVID‐19: From cytopenia to coagulopathy
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Coronavirus Disease 2019 (COVID-19) and Nutritional Status: The Missing Link?
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“Hematopoietic tissue (106, 107), lymphocyte number (108), proliferative and functional capacity of effector lymphocytes (107), and activity of NK cells (109) are all reduced in the elderly.”
BackgroundDemodex species in human ocular disease: new clinicopathological aspects
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The management of community-acquired pneumonia in the elderly
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“According to recent literature, there is a remodeling of the immune system during senescence: a reduced production of B and T cells in the bone marrow and thymus and diminished function of mature lymphocytes [55,56].”
BackgroundLymphocyte maintenance during healthy aging requires no substantial alterations in cellular turnover
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“Advanced aging is associated with greater susceptibility to infections, reduced vaccine efficacy, and a higher incidence of cancer and autoimmune disease (Goronzy & Weyand, 2013; Montecino-Rodriguez et al. , 2013).”
Age-related mitochondrial dysfunction as a key factor in COVID-19 disease
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Immunosenescence and Novel Vaccination Strategies for the Elderly
Dorrington, M. G., & Bowdish, D. M. E. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00171 · Cited by 104
Understanding and targeting prostate cancer cell heterogeneity and plasticity
Tang, D. G. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.11.001 · Cited by 102
“How do the LP cells (or other prostate epithelial cells) become trans- formed into tumor cells?—As PCa manifests a distinct association with age and LPs accumulate and expand in the aging prostate [24], it is reasonable to speculate that PCa etiology may be linked to immune senescence and impaired immune surveillance…”
BackgroundImmunomodulatory functional foods and their molecular mechanisms
Kim, J. H., Kim, D. H., Jo, S., Cho, M. J., Cho, Y. R., Lee, Y. J., & Byun, S. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00724-0 · Cited by 112
Classifying aging as a disease in the context of ICD-11
Zhavoronkov, A. A., & Bhullar, B. (2015) · Frontiers in Genetics · doi:10.3389/fgene.2015.00326 · Cited by 103
“…et al., 2013;Deleidi et al., 2015), cause and effect relationships between different processes and systems, including aging of the immune system (Montecino-Rodriguez et al., 2013), inflammation (Bruunsgaard et al., 2001;Sarkar and Fisher, 2006;Franceschi et al., 2007;Michaud et al., 2013),…”
BackgroundInhibition of B Lymphopoiesis by Adipocytes and IL-1–Producing Myeloid-Derived Suppressor Cells
Kennedy, D. E., & Knight, K. L. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500957 · Cited by 97
Benedyk, M., Mydel, P. M., Delaleu, N., Płaza, K., Gawron, K., Milewska, A., Maresz, K., Koziel, J., Pyrc, K., & Potempa, J. (2016) · Journal of Innate Immunity · doi:10.1159/000441724 · Cited by 98
Channappanavar, R., & Perlman, S. M. (2020) · Journal of Clinical Investigation · doi:10.1172/jci144115 · Cited by 94
Delayed decompression exacerbates ischemia-reperfusion injury in cervical compressive myelopathy
Vidal, P. M., Karadimas, S. K., Ulndreaj, A., Laliberté, A. M., Tetreault, L. A., Forner, S., Wang, J., Foltz, W. D., & Fehlings, M. G. (2017) · JCI Insight · doi:10.1172/jci.insight.92512 · Cited by 99
“Our results are in agreement with the work of others in the literature, showing that the immune response can decrease with age (17, 60).”
BackgroundResultDo haematopoietic stem cells age?
Dorshkind, K. A., Höfer, T., Montecino‐Rodriguez, E., Pioli, P. D., & Rodewald, H.-R. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0236-2 · Cited by 92
Self-citationDu, F., Liu, B., & Zhang, S. (2020) · Journal of Thrombosis and Thrombolysis · doi:10.1007/s11239-020-02224-2 · Cited by 92
“An aged immune system is not only associated with a decreased efficiency for virus clearance due to declined B and T cell productions and functions, leading to constant viral exposure and excessive inflammations, but also associated with an increased propensity for excessive pro-inflammatory cytokine release because o…”
BackgroundElyahu, Y., & Monsonego, A. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101231 · Cited by 93
COVID-19: Inflammatory Profile
Wang, Y., & Perlman, S. M. (2021) · Annual Review of Medicine · doi:10.1146/annurev-med-042220-012417 · Cited by 93
Immune system modulation in aging: Molecular mechanisms and therapeutic targets
Cisneros, B., García‐Aguirre, I., Unzueta, J., Arrieta‐Cruz, I., González-Morales, O., Domínguez-Larrieta, J. M., Tamez-González, A., Leyva‐Gómez, G., & Magaña, J. J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1059173 · Cited by 97
Identification of long-lived proteins retained in cells undergoing repeated asymmetric divisions
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“There is good evidence that some stem cells have an age-associated decline, including those in muscle, the Germ-line, hematopoietic/ immune systems, epithelium, and neurons (10, 11, 60, 61).”
BackgroundImmunosenescence and vaccine failure in the elderly: strategies for improving response
Boraschi, D., & Italiani, P. (2014) · Immunology Letters · doi:10.1016/j.imlet.2014.06.006 · Cited by 86
T Cell Immunosenescence in Aging, Obesity, and Cardiovascular Disease
Shirakawa, K., & Sano, M. (2021) · Cells · doi:10.3390/cells10092435 · Cited by 89
“Since naïve T cells in the periphery are primarily maintained by homeostatic proliferation after thymic involution, there is no doubt that T cells are strongly affected by aging, unlike other immune cell types that depend on the production of hematopoietic stem cells (HSCs) [31,32].”
BackgroundGeriatric Infectious Diseases: Current Concepts on Diagnosis and Management
Yoshikawa, T. T., & Norman, D. C. (2017) · Journal of the American Geriatrics Society · doi:10.1111/jgs.14731 · Cited by 98
BRAFV600E-induced senescence drives Langerhans cell histiocytosis pathophysiology
Bigenwald, C., Le Berichel, J., Wilk, C. M., Chakraborty, R., Chen, S. T., Tabachnikova, A., Mancusi, R., Abhyankar, H., Casanova-Acebes, M., Laface, I., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01304-x · Cited by 83
Maine, G. N., Lao, K. M., Krishnan, S. M., Afolayan-Oloye, O. I., Fatemi, S., Kumar, S., VanHorn, L., Hurand, A., Sykes, E., & Sun, Q. (2020) · Journal of Clinical Virology · doi:10.1016/j.jcv.2020.104663 · Cited by 81
Kang, Y., Zhang, H., Zhao, Y., Wang, Y., Wang, W. T., He, Y., Zhang, W. K., Zhang, W., Zhu, X., Zhou, Y., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.071 · Cited by 83
Jung, H., Kim, D. O., Byun, J.-E., Kim, W. S., Kim, M. J., Song, H. Y., Kim, Y. K., Kang, D.-K., Park, Y.-J., Kim, T.-D., et al. (2016) · Nature Communications · doi:10.1038/ncomms13674 · Cited by 81
Impact of the Microbiome on the Immune System
Lambring, C. B., Siraj, S., Patel, K. J., Sankpal, U. T., Mathew, S. O., & Basha, R. M. (2019) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.2019033233 · Cited by 82
Montecino‐Rodriguez, E., Kong, Y., Casero, D., Rouault, A., Dorshkind, K. A., & Pioli, P. D. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2019.01.016 · Cited by 79
“The Number of Ly-HSCs Does Not Decline with Age Current models propose that the number of Ly-HSCs declines and that the number of My-HSCs increases with age (Elias et al., 2016; Montecino-Rodriguez et al., 2013; Muller-Sieburg et al., 2004).”
BackgroundMethodResultInfluentialSelf-citationSauce, D., Dong, Y., Campillo-Gimenez, L., Casulli, S., Bayard, C., Autran, B., Boddaert, J., Appay, V., & Elbim, C. (2016) · The Journals of Gerontology Series A · doi:10.1093/gerona/glw062 · Cited by 83
“The impact of aging on immunity has been mainly addressed within the context of the acquired arm of the immune system, generally referring to the altered functions of CD4+ and CD8+ T lymphocytes (3).”
Background
Metadata
- Authors
- Montecino-Rodriguez, E., Berent-Maoz, B., & Dorshkind, K.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Dorshkind, Kenneth
- Venue
- Journal of Clinical Investigation
- Published
- 2013-03-01
- Volume
- 123
- Issue
- 3
- Pages
- 958-965
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3582124
- OpenAlex
- W1978103330
- Semantic Scholar
- 21eeafabbc2cc60c6c46752d238c5688d989e17b
- Cited by
- 793
- References
- 120
- Citations by year
- 2026: 30 · 2025: 47 · 2024: 72 · 2023: 86 · 2022: 96 · 2021: 126 · 2020: 106 · 2019: 64 · 2018: 54 · 2017: 37 · 2016: 21 · 2015: 27 · 2014: 18 · 2013: 9
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R01AG034875, AG034875)
- David Geffen School of Medicine, University of California, Los Angeles
- 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 › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- immunosenescence, B cell aging, T cell senescence, thymus, bone marrow, secondary lymphoid organs, lymphocyte function
- MeSH terms
- Aging, Animals, Hematopoietic Stem Cells, Humans, Immune System, Immunologic Factors, Lymphoid Progenitor Cells
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