Is immunosenescence influenced by our lifetime “dose” of exercise?
Open accessAbstract
The age-associated decline in immune function, referred to as immunosenescence, is well characterised within the adaptive immune system, and in particular, among T cells. Hallmarks of immunosenescence measured in the T cell pool, include low numbers and proportions of naïve cells, high numbers and proportions of late-stage differentiated effector memory cells, poor proliferative responses to mitogens, and a CD4:CD8 ratio <1.0. These changes are largely driven by infection with Cytomegalovirus, which has been directly linked with increased inflammatory activity, poor responses to vaccination, frailty, accelerated cognitive decline, and early mortality. It has been suggested however, that exercise might exert an anti-immunosenescence effect, perhaps delaying the onset of immunological ageing or even rejuvenating aged immune profiles. This theory has been developed on the basis of evidence that exercise is a powerful stimulus of immune function. For example, in vivo antibody responses to novel antigens can be improved with just minutes of exercise undertaken at the time of vaccination. Further, lymphocyte immune-surveillance, whereby cells search tissues for antigens derived from viruses, bacteria, or malignant transformation, is thought to be facilitated by the transient lymphocytosis and subsequent lymphocytopenia induced by exercise bouts. Moreover, some forms of exercise are anti-inflammatory, and if repeated regularly over the lifespan, there is a lower morbidity and mortality from diseases with an immunological and inflammatory aetiology. The aim of this article is to discuss recent theories for how exercise might influence T cell immunosenescence, exploring themes in the context of hotly debated issues in immunology.
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Written from the paper’s full text.
TL;DR
This narrative review discusses whether lifetime exercise “dose” influences T cell immunosenescence, focusing on the “exercise makes immunological space” hypothesis and evidence for a U-shaped relationship. It concludes that moderate exercise may have anti-immunosenescence effects up to a threshold, whereas very high-volume endurance exercise may be pro-immunosenescence, but evidence is limited and mechanisms remain debated.
Key findings
- Accepted hallmarks of immunosenescence include low numbers/proportions of naïve T cells, high late-stage differentiated memory T cells, poor T cell proliferative responses to mitogens, and a CD4:CD8 ratio <1.0; CMV is central, with approximately 10 % of the CD4+ and CD8+ T cell pool becoming CMV-specific and up to 23 % of the CD8+ pool specific for a single CMV epitope. The Immune Risk Profile predicted greater all-cause mortality at 2-, 4-, and 6-year follow-up.
- The proposed “exercise makes immunological space” hypothesis suggests exercise mobilises late-stage differentiated T cells into blood, they extravasate to tissues and may undergo selective apoptosis, and naïve T cells may expand via thymic or extrathymic output. However, the paper notes debate over whether late-stage differentiated T cells are truly senescent, whether they are susceptible to apoptosis, and whether immunological “space” is fixed.
- In 102 males aged 18–61 years, late-stage differentiated CD4+ and CD8+ T cell proportions were inversely correlated with cardiorespiratory fitness, and the age-associated decrease in naïve T cells and increase in late-stage differentiated T cells did not withstand statistical adjustment for cardiorespiratory fitness. In a study of 8 trained and 8 untrained males plus 8 trained and 8 untrained females (approximately 18 years), untrained individuals had the highest proportions of late-stage differentiated CD4+ and CD8+ cells and lowest CD8+ naïve cells, but effects were largely sex-dependent.
- High-volume endurance exercise may be pro-immunosenescence: young endurance athletes (n = 27) showed greater late-stage differentiated CD4+ T cells, lower CD4:CD8 ratio, poor T cell activation to anti-CD3, and reduced thymic output versus less-active controls (n = 30); another athlete group (n = 19) had lower naïve and higher memory T cells and TREC levels comparable to the sixth decade. A small study (n = 5 well-trained males aged 20–26 years) found no substantial change in late-stage differentiated CD4+ and CD8+ T cells at 10 and 24 h after 60 min treadmill running at 80 % VO2max. Overall, the paper proposes a U-shaped relationship between exercise and T cell immunosenescence.
Methods
- Narrative review and theoretical discussion; no primary data collection or new experimental sample.
- Synthesises existing exercise immunology and immunogerontology literature, including cross-sectional and longitudinal studies of exercise/fitness and T cell phenotypes, plus mechanistic studies on CMV, apoptosis, redox balance, and thymic output.
- Proposes a hypothetical dose–response model (Fig. 1) relating lifetime exercise exposure to the rate or degree of immunosenescence.
Limitations
- Stated in the paper: evidence is limited, the relationship between exercise volume and immunosenescence is probably not linear, and it is likely influenced by lifetime accumulation of exercise behaviour. Methodological concerns include self-reported physical activity, use of proportions rather than absolute cell numbers, inconsistent sample timing and diurnal rhythms, non-uniform participant characteristics (e.g., age, training load, menstrual cycle, CMV serostatus), and inability to identify truly senescent/exhausted cells with surface markers alone.
- Stated in the paper: it remains unclear whether senescent late-stage differentiated T cells can be eliminated by apoptosis after exercise, whether thymic output depends on available “space,” and whether findings generalise to CMV-seronegative individuals.
- Evident from the text: this is a narrative review rather than a systematic review or meta-analysis, and many cited exercise studies are small, heterogeneous, and not designed to directly test the proposed causal mechanisms.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
0 of 206 cited sources checked · 0 supported · 0 flagged
- Premisecitation
In vivo antibody responses to novel antigens can be improved with just minutes of exercise undertaken at the time of vaccination.
“For example, in vivo antibody responses to novel antigens can be improved with just minutes of exercise undertaken at the time of vaccination.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Pascoe et al. 2014 source
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- Premisecitation
Some forms of exercise are anti-inflammatory.
“Moreover, some forms of exercise are anti-inflammatory, and if repeated regularly over the lifespan, there is a lower morbidity and mortality from diseases with an immunological and inflammatory aetiology.”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
These immunosenescence changes are largely driven by infection with Cytomegalovirus.
“These changes are largely driven by infection with Cytomegalovirus, which has been directly linked with increased inflammatory activity, poor responses to vaccination, frailty, accelerated cognitive decline, and early mortality.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Olsson et al. 2000 source
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- cites Pawelec 2012, 2013
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- Interpretationreasoning
The dose-dependent effect of exercise is a product of the mode, duration, intensity, and frequency of exercise, culminating in a lifetime exposure and possible accumulation of effects.
“This “dose” dependent effect is a product of the mode, duration, intensity, and frequency of exercise, which in the context of ageing, culminates in a lifetime exposure and possible accumulation of effects.”
Quote in the paperSubstantial claim - Premisereasoning
If exercise is repeated regularly over the lifespan, there is lower morbidity and mortality from diseases with an immunological and inflammatory aetiology.
“Moreover, some forms of exercise are anti-inflammatory, and if repeated regularly over the lifespan, there is a lower morbidity and mortality from diseases with an immunological and inflammatory aetiology.”
Quote in the paperSubstantial claim0 of 2 sources checked
- Premisecitation
Exercise is a powerful stimulus of immune function.
“This theory has been developed on the basis of evidence that exercise is a powerful stimulus of immune function.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Walsh et al. 2011a,b
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- Study design and conductcitation
Depending on the specific criteria used from physical activity guidelines and the analytical decisions made, it is possible to describe the same individual as 'active' but also 'inactive'.
“For example, depending on the specific criteria used from physical activity guidelines, and the analytical decisions made, it is possible to describe the same individual as “active” but also “inactive” (i.e., failing to meet physical activity recommendations) (Thompson et al. 2009).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Thompson et al. 2009 source
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- Premisecitation
Acute bouts of exercise have been shown to improve or 'stimulate' aspects of immune function that decline with ageing.
“Importantly, acute bouts of exercise have been shown to improve or “stimulate” aspects of immune function that decline with ageing (Walsh et al. 2011b).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Walsh et al. 2011b
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- Premisecitation
Cross-sectional studies have highlighted that 'active' individuals exhibit better immune function than 'inactive' individuals, even in the elderly.
“Cross-sectional studies have highlighted that “active” individuals exhibit better immune function than “inactive” individuals, even in the elderly (Kohut and Senchina 2004; Simpson et al. 2012).”
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- cites Simpson et al. 2012 source
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- Premisecitation
These characteristics, in combination with thymic involution, result in decreased numbers and proportions of CD4+ and CD8+ naïve T cells.
“These characteristics, in combination with thymic involution, result in decreased numbers and proportions of CD4+ and CD8+ naïve T cells (Appay and Sauce 2014; Fulop et al. 2013; Pawelec 2012, 2013).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Premisecitation
Ageing results in alterations to almost all aspects of innate and adaptive immune function.
“Ageing results in alterations to almost all aspects of innate and adaptive immune function, and these changes are typically assumed to reflect deregulation.”
Quote in the paperSubstantial claim0 of 2 sources checked - Study design and conductcitation
Acute exercise-induced changes in some immunological variables can only be characterised accurately if sample timing is optimal due to transient lymphocyte trafficking patterns.
“For example, acute exercise-induced changes in some immunological variables (e.g., blood lymphocyte number, phenotype and cell subset composition) can only be characterised accurately if sample timing is optimal due to transient lymphocyte trafficking patterns (for a time course of changes, see Gabriel and Kindermann 1997; Gleeson and Bishop 2005).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Gabriel and Kindermann 1997 source
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- cites Gleeson and Bishop 2005
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- Premisecitation
Extreme exercise, such as ultra-endurance races, is associated with very large, and sometimes prolonged, immunological and inflammatory disturbances.
“At the far end of this scale, it is known that extreme exercise, such as ultra-endurance races (i.e., exercise performed over large parts of a day or several consecutive days with little or no rest), is associated with very large, and sometimes prolonged, immunological and inflammatory disturbances (Turner et al. 2011, 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Turner et al. 2011, 2013
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- Premisecitation
The acute effects of exercise include improvements in the trafficking and functional capabilities of many cell types, including haematopoietic stem cells, cells of myeloid lineage, and cells of lymphoid lineage.
“The acute effects of exercise include improvements in the trafficking and functional capabilities of many cell types, including haematopoietic stem cells (Thijssen et al. 2006), cells of myeloid lineage (e.g., monocytes, neutrophils, dendritic cells) and cells of lymphoid lineage (e.g., NK cells, B cells and T cells) (Shephard 2003; Walsh et al. 2011b).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Premisecitation
Together, the IRP characteristics predicted greater all-cause mortality at 2-, 4- and 6-year follow up.
“In addition, infection with CMV was also clustered into the IRP (Olsson et al. 2000) and together, these characteristics predicted greater all-cause mortality at 2-, 4- and 6-year follow up.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Wikby et al. 1994, 1998
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- Premisecitation
Cells of a late-stage differentiated phenotype are mobilised into peripheral blood during exercise.
“First, as shown by many investigations (e.g., Campbell et al. 2009; Simpson et al. 2007, 2010; Turner et al. 2010), cells of a late-stage differentiated phenotype are mobilised into peripheral blood during exercise.”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Skeletal muscle secretes IL-7.
“A post-exercise surge in thymopoiesis is possible considering that skeletal muscle secretes IL-7 (Haugen et al. 2010) which might in turn increase thymic mass and lead to the emergence of recent thymic emigrants (Fry and Mackall 2005).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Haugen et al. 2010 source
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- Premisecitation
Lymphocyte apoptosis occurs post-exercise in tissues that are thought to be the homing destination of mobilised cells in mice.
“This assertion is partly supported by observations in mice, showing that lymphocyte apoptosis occurs post-exercise in tissues that are thought to be the homing destination of mobilised cells (Kruger et al. 2009).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Kruger et al. 2009 source
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- Premisecitation
Longitudinal studies of octogenarians in exceptional health, and nonagenarians, revealed a cluster of parameters referred to as the 'Immune Risk Profile' (IRP).
“Longitudinal studies of octogenarians in exceptional health, and nonagenarians, with health profiles more representative of this age group, revealed a cluster of parameters that were referred to as the “Immune Risk Profile” (IRP) (Pawelec et al. 2001; Wikby et al. 1994, 1998).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Pawelec et al. 2001 source
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- cites Wikby et al. 1994, 1998
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- Premisecitation
These cells extravasate from blood, homing to peripheral and/or inflamed tissues 1-2 h after exercise.
“Second, in line with current thinking in exercise immunology (Dhabhar 2014; Walsh et al. 2011a, b), these cells extravasate from blood, homing to peripheral and/or inflamed tissues 1–2 h after exercise.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Dhabhar 2014 source
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- cites Walsh et al. 2011a,b
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- Premisecitation
Infection with CMV causes a large accumulation of virus-specific memory T cells, so that approximately 10% of the CD4+ and CD8+ T cell pool becomes specific for this virus.
“Infection with CMV causes a large accumulation of virus-specific memory T cells, so that approximately 10 % of the CD4+ and CD8+ T cell pool becomes specific for this virus (Sylwester et al. 2005).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Sylwester et al. 2005 source
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- Premisecitation
Acute bouts of exercise and exercise training interventions have been shown to improve in vivo immune responses in the young and elderly, such as antibody responses to influenza vaccines.
“Moreover, acute bouts of exercise (and also exercise training interventions) have been shown to improve in vivo immune responses in the young and elderly, such as antibody responses to influenza vaccines (Pascoe et al. 2014).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Pascoe et al. 2014 source
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- Premisecitation
Infection with CMV was also clustered into the IRP.
“In addition, infection with CMV was also clustered into the IRP (Olsson et al. 2000) and together, these characteristics predicted greater all-cause mortality at 2-, 4- and 6-year follow up.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Olsson et al. 2000 source
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- Premisecitation
Even in vaccine studies that have not directly investigated, characterised or controlled for the degree of immunological ageing in the volunteers examined, acute and chronic exercise can improve the response to in vivo novel antigen challenge.
“Encouragingly though, even in vaccine studies that have not directly investigated, characterised or controlled for the degree of immunological ageing in the volunteers examined, it has been shown that acute and chronic exercise can improve the response to this in vivo novel antigen challenge (de Araujo et al. 2015; Pascoe et al. 2014).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Higher inflammatory activity, measured by plasma or serum interleukin (IL)-6, tumour necrosis factor-α (TNF-α) and C-reactive protein (CRP), has also been associated with shorter survival.
“In addition, higher inflammatory activity, measured by plasma or serum interleukin (IL)-6, tumour necrosis factor-α (TNF-α) and C-reactive protein (CRP), has also been associated with shorter survival (Baune et al. 2011; Bruunsgaard et al. 2003; Giovannini et al. 2011).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Premisecitation
CMV-specific T cells exhibit a late-stage differentiated phenotype, including loss of co-stimulatory molecules (e.g., CD27 and CD28) and cell-surface proteins associated with homing to lymphoid tissue (e.g., CD62L and CCR7).
“These CMV-specific T cells exhibit a late-stage differentiated phenotype, including loss of co-stimulatory molecules (e.g., CD27 and CD28) and cell-surface proteins associated with homing to lymphoid tissue (e.g., CD62L and CCR7) (Appay et al. 2008; van Lier et al. 2003).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
These cells re-express CD45RA in combination with markers often stated to reflect 'senescence' such as CD57 and KLRG1.
“Further, these cells re-express CD45RA in combination with markers often stated to reflect “senescence” such as CD57 and KLRG1 (Appay et al. 2008; van Lier et al. 2003).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
One of the first studies to describe CMV-specific cells as being dysfunctional did so because the proportion of antigen-stimulated interferon-gamma (IFN-γ) producing cells from elderly people was lower than in young people.
“One of the first studies to describe CMV-specific cells as being dysfunctional, did so because the proportion of antigen-stimulated interferon-gamma (IFN-γ) producing cells from elderly people, was lower than in young people (Ouyang et al. 2003a).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Ouyang et al. 2003a
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- Premisecitation
T cells expressing CD57 and KLRG1 are more susceptible to H2O2-induced apoptosis than total lymphocytes and naive phenotype cells in vitro.
“T cells expressing cell-surface proteins associated with differentiation or “senescence” (e.g., CD57 and KLRG1) are more susceptible to H2O2 induced apoptosis than total lymphocytes (Wang and Lin 2010) and cells of a naïve phenotype (e.g., CD45RA + CCR7+) in vitro (Takahashi et al. 2005).”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationreasoning
It is very difficult to enumerate all CMV-specific cells in an individual using peptide-MHC multimer technology.
“Thus, it is very difficult to enumerate all CMV-specific cells in an individual using this technology.”
Quote in the paperSubstantial claim - Premisecitation
Many CMV-specific CD8+ T cells, identified using MHC-class I tetramers, are multifunctional, producing IFN-γ, IL-2 and TNF-α.
“Moreover, recent work has shown that many CMV-specific CD8+ T cells, identified using MHC-class I tetramers, are multifunctional, producing IFN-γ, IL-2 and TNF-α (Riddell et al. 2015).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Riddell et al. 2015 source
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- Interpretationcitation
There may be an age threshold before which anti-immunosenescence interventions must be initiated.
“suggesting there may be an age threshold before which anti-immunosenescence interventions must be initiated.”
Quote in the paperSubstantial claim - Premisecitation
Thymic output persists, albeit reduced, up until around 70 years of age.
“While studies continue to support the age-associated reduction in thymic function, evidence now points towards a more gradual decline, whereby thymic output persists, albeit reduced, up until around 70 years of age (Douek et al. 1998; Ferrando-Martinez et al. 2010).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Interpretationreasoning
Fully functioning late-stage differentiated T cells have an important role in controlling latent viruses.
“This finding highlights the important role that fully functioning late-stage differentiated T cells have in controlling latent viruses.”
Quote in the paperSubstantial claim - Interpretationcitation
Even in healthy individuals, the latest evidence points towards an essential role for immune-surveillance of CMV.
“Even in healthy individuals, the latest evidence points towards an essential role for immune-surveillance of CMV.”
Quote in the paperSubstantial claim - Interpretationnone given
Analysis of cell surface proteins alone is not sufficient to discriminate between fully functioning late-stage differentiated cells and those that are truly senescent and functionally exhausted.
“Analysis of cell surface proteins alone is not sufficient to discriminate between fully functioning late-stage differentiated cells and those that are truly senescent and functionally exhausted (see next section).”
Quote in the paperNot a substantial claim - Premisecitation
In the context of solid organ or stem cell transplant, there is substantial morbidity and mortality from CMV reactivation and subsequent disease, in part due to loss or suppression of cell-mediated immunity.
“In the context of solid organ or stem cell transplant, there is substantial morbidity and mortality from CMV reactivation and subsequent disease, in part, due to loss or suppression, of cell-mediated immunity (Stocchi et al. 1999).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Stocchi et al. 1999
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- Premisecitation
In CMV seronegative patients before and after transplantation with a CMV-infected kidney, there is a long-lasting enlargement of the CD8+ T cell compartment.
“in an analysis of total CD8+ T cells and virus-specific CD8+ T cells from CMV seronegative patients before and after transplantation with a CMV-infected kidney, it was concluded that there is a long-lasting enlargement of the CD8+ T cell compartment (van Leeuwen et al. 2006).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites van Leeuwen et al. 2006 source
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- Interpretationcitation
These cells might not classify as being senescent due to this multifunctional phenotype alone.
“Therefore these cells might not classify as being senescent due to this multifunctional phenotype alone.”
Quote in the paperSubstantial claim - Interpretationreasoning
It is imprecise to refer to all late-stage differentiated T cells as being 'senescent'.
“To conclude, for the reasons described above, it is imprecise to refer to all late-stage differentiated T cells as being “senescent”.”
Quote in the paperSubstantial claim - Premisecitation
Cells in a state of SIPS, brought about independently of telomere shortening, exhibit a proteomic profile that is distinct from cells that have undergone replicative senescence.
“Studies have shown that cells in a state of SIPS, brought about independently of telomere shortening, exhibit a proteomic profile that is distinct from cells that have undergone replicative senescence (Aan et al. 2013; Dierick et al. 2002).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
CMV-specific CD8+ T cells are equally as susceptible to Fas-L/Fas-R induced apoptosis as the total pool of CD8+ T cells.
“CMV-specific CD8+ T cells, rather than being resistant to apoptosis, are equally as susceptible to Fas-L/Fas-R induced apoptosis as the total pool of CD8+ T cells (Mueller et al. 2001).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Mueller et al. 2001 source
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- Premisecitation
The cumulative IFN-γ production was higher in the elderly due to greater absolute numbers of these cells compared to the young.
“However, the cumulative IFN-γ production was higher in the elderly due to greater absolute numbers of these cells compared to the young (Ouyang et al. 2003a).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Ouyang et al. 2003a
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- Premisecitation
The antioxidant effects on T cell clones were not replicated in T cell clones from an elderly donor despite conforming to SENIEUR protocol criteria.
“Critically, these effects were not replicated in T cell clones from an elderly donor (Marthandan et al. 2014) despite conforming to SENIEUR protocol criteria (Ligthart et al. 1984, 1990)”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Marthandan et al. 2014 source
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- cites Ligthart et al. 1984, 1990
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- Premisecitation
The view that many late-stage differentiated cells are not dysfunctional or senescent is supported by studies showing that programmed death-1 (PD-1) is expressed on very few CMV-specific cells and at low levels.
“The view that many of these late-stage differentiated cells are not dysfunctional or senescent is supported by studies showing that the inhibitory molecule programmed death-1 (PD-1) is expressed on very few CMV-specific cells and at low levels (Petrovas et al. 2006; Trautmann et al. 2006).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
CD4+ T cells become more susceptible to apoptosis with in vitro age.
“It appears however, that CD4+ T cells become more susceptible to apoptosis with in vitro age (Pawelec et al. 1996).”
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- Premisecitation
These cells have telomeres of intermediate length, despite 'senescent' cell-surface characteristics (e.g., CD45RA+CD27−).
“In addition, these cells have telomeres of intermediate length, despite “senescent” cell-surface characteristics (e.g., CD45RA + CD27−) (Riddell et al. 2015).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Riddell et al. 2015 source
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- Premisecitation
Peptide-MHC class-I or class-II multimers can estimate the extent of CMV 'obsession' by identifying antigen-specific cells.
“Studies can estimate the extent of CMV “obsession” by identifying antigen-specific cells using peptide-MHC class-I or class-II multimers (Altman et al. 1996; Davis et al. 2011).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Study design and conductcitation
This methodology will not identify the proportion of antigen-specific cells that are senescent/exhausted, unless functional measurements are incorporated in tandem or post hoc.
“Moreover, this methodology will not identify the proportion of antigen-specific cells that are senescent/exhausted, unless functional measurements are incorporated in tandem or post hoc (Borchers et al. 2014; Klenerman et al. 2002).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Protocols have been developed to adoptively transfer CMV-specific CD8+ T cells to prevent viral reactivation in transplant recipients.
“The importance of T cells targeting CMV is emphasised by protocols that have been developed to adoptively transfer CMV-specific CD8+ T cells to prevent viral reactivation in transplant recipients (Cobbold et al. 2005).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Cobbold et al. 2005 source
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- Premisecitation
TEMRA cells generally become dysfunctional.
“Generally, it is TEMRA cells that become dysfunctional (Fulop et al. 2013; van Lier et al. 2003)”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
TEMRA cells do not accumulate in elderly CMV seronegative individuals.
“as TEMRA cells do not accumulate in elderly CMV seronegative individuals (Wertheimer et al. 2014)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Wertheimer et al. 2014 source
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- Interpretationreasoning
A removal of senescent T cells probably only applies to individuals infected with CMV.
“Thus, as TEMRA cells do not accumulate in elderly CMV seronegative individuals (Wertheimer et al. 2014) a removal of senescent T cells probably only applies to those infected with CMV.”
Quote in the paperSubstantial claim - Premisecitation
The percentage of the CD4+ and CD8+ T cell pool comprising late-stage differentiated T cells was inversely correlated with cardiorespiratory fitness in 102 males aged 18-61 years.
“One of the first papers leading to, and providing experimental evidence for the hypothesis that “exercise makes immunological space”, showed that the percentage of the CD4+ and CD8+ T cell pool comprising late-stage differentiated T cells was inversely correlated with cardiorespiratory fitness (i.e., ) in 102 males aged 18–61 years (Spielmann et al. 2011).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Spielmann et al. 2011 source
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- Premisecitation
Over approximately 6 months, numbers and proportions of CD4+ and CD8+ late-stage differentiated T cells accumulate whereas CD4+ and CD8+ naive cells decrease in endurance athletes.
“These studies show that over approximately 6 months, the numbers and proportions of CD4+ and CD8+ late-stage differentiated T cells accumulate whereas CD4+ and CD8+ naïve cells decrease (Cosgrove et al. 2012; Teixeira et al. 2014).”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationreasoning
An anti-immunosenescence effect of exercise might only occur up to a threshold of lifetime exercise exposure (e.g., one to three multiples of recommended duration, intensity and frequency per week).
“Moreover, it seems that an anti-immunosenescence effect of exercise might only occur up to a threshold of lifetime exercise exposure (e.g., one to three multiples of the duration, intensity and frequency of exercise recommended by physical activity guidelines per week; see Fig. 1).”
Quote in the paperNot a substantial claim - Interpretationcitation
Very large volumes of exercise elicit a pro-immunosenescence effect.
“Studies collecting resting blood samples from endurance athletes and from less-active controls (defined using self-reported physical activity level), suggest that very large volumes of exercise elicit a pro-immunosenescence effect.”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationcitation
In active individuals or those exposed to moderate-to-high volumes of exercise over a short period, exercise likely exerts an anti-immunosenescence effect in a dose-dependent manner until a certain threshold.
“When examining individuals described as being active or those who have been exposed to moderate-to-high volumes of exercise over a short period of the lifespan (e.g., young adults), it is likely that exercise exerts an anti-immunosenescence effect in a dose-dependent manner until a certain threshold (Brown et al. 2014; Spielmann et al. 2011).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
After exercise, total lymphocyte count returns to pre-exercise levels within approximately 6-10 h.
“after exercise the total lymphocyte count returns to pre-exercise levels within approximately 6–10 h (Gabriel and Kindermann 1997; Gleeson and Bishop 2005)”
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- cites Gleeson and Bishop 2005
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- Interpretationreasoning
Active or very active individuals exhibit favourable changes to immune function that result in robust and sustained responses to novel antigens.
“Active or very active individuals (middle triangle) exhibit favourable changes to immune function that results in robust and sustained responses to novel antigens.”
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CMV reactivation causes an expansion of TEMRA cells, compared to other persistent infections that periodically reactivate (e.g., EBV).
“compared to other persistent infections that periodically reactivate (e.g., EBV) it is CMV reactivation that causes an expansion of these cells (Cantisan et al. 2009; Fulop et al. 2013; Gamadia et al. 2004).”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationreasoning
Based on limited evidence, the relationship between exercise and T cell immunosenescence is U-shaped.
“Thus, based on the limited evidence to date, it appears that the relationship between exercise and T cell immunosenescence is U-shaped.”
Quote in the paperSubstantial claim - Premisecitation
Sedentary lifestyles, characterised by inactive skeletal muscle, sarcopenia and adipose tissue accumulation, are associated with moderate-to-high levels of reactive oxygen species, which can deplete antioxidant defences resulting in oxidation of proteins, lipids and DNA.
“Sedentary lifestyles, characterised by inactive skeletal muscle, sarcopenia and adipose tissue accumulation, are associated with moderate-to-high levels of reactive oxygen species, which can deplete antioxidant defences resulting in oxidation of proteins, lipids and DNA (Bjork et al. 2012; Derbre et al. 2014; Gratas-Delamarche et al. 2014; Le Lay and Simard 2014).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
In initial observations (n = 5 healthy well-trained males aged 20-26 years), numbers and proportions of late-stage differentiated CD4+ and CD8+ T cells measured 10 and 24 h after 60 min of treadmill-running at 80% are not substantially different from pre-exercise levels.
“Initial observations (n = 5 healthy well-trained males aged 20–26 years) indicate that the numbers and proportions of late-stage differentiated CD4+ and CD8+ T cells, measured 10 and 24 h after 60 min of treadmill-running at 80 % , are not substantially different from pre-exercise levels (Turner et al. 2016).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Turner et al. 2016
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- Interpretationreasoning
Elite endurance athletes or ultra-endurance athletes might exhibit exacerbated immunosenescent profiles compared to active individuals.
“At the extreme end of the exercise continuum, elite endurance athletes, or ultra-endurance athletes, who have engaged in frequent, intensive and prolonged exercise over a substantial period of time, might exhibit exacerbated immunosenescent profiles compared to active individuals.”
Quote in the paperSubstantial claim - Interpretationcitation
If exercise stimulates thymic or extra-thymic output of naïve T cells, this feature of an anti-immunosenescence intervention might be beneficial for all individuals.
“However, if exercise stimulates thymic or extra-thymic output of naïve T cells, this feature of an anti-immunosenescence intervention might be beneficial for all individuals”
Quote in the paperSubstantial claim - Interpretationreasoning
The relationship between reactive oxygen species production and exercise across the exercise continuum is likely J-shaped, as with infection risk.
“However, emerging evidence suggests that the relationship across the exercise continuum, as with infection risk, is likely to be J-shaped.”
Quote in the paperSubstantial claim - Premisecitation
A recent murine study showed that 24 h after acute exercise, lymphocytes undergo apoptosis in peripheral blood and bone marrow, in parallel with an increase of haematopoietic stem cells at these sites.
“a recent murine study has shown that 24 h after an acute bout of exercise, lymphocytes undergo apoptosis in peripheral blood and bone marrow, which occurs in parallel with an increase of haematopoietic stem cells at these sites (Mooren and Kruger 2015a).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Mooren and Kruger 2015a
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- Premisecitation
Naïve T cells decline with age even in individuals not infected with CMV.
“considering the age-associated decline of these cells even in those not infected with CMV (Vescovini et al. 2013; Wertheimer et al. 2014).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
At the extreme end of the exercise continuum, very prolonged and/or intensive bouts of exercise result in substantial oxidative stress.
“At the extreme end of the exercise continuum, very prolonged and/or intensive bouts of exercise result in substantial oxidative stress (Knez et al. 2006).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Knez et al. 2006 source
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- Premisecitation
Individuals over the age of 60 years with a CD4:CD8 ratio <1.0 exhibit high levels of plasma advanced oxidation products and high plasma antioxidant capacity, indicative of a compensatory 'antioxidant response' to oxidative stress.
“For example, it has been shown that individuals over the age of 60 years, with a CD4:CD8 ratio <1.0, exhibit high levels of plasma advanced oxidation products, and high plasma antioxidant capacity—indicative of a compensatory “antioxidant response” to oxidative stress (Muller et al. 2015).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Muller et al. 2015 source
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- Premisecitation
A murine study has shown that N-acetyl-cysteine prevents thymocyte apoptosis and cell loss caused by exercise-induced oxidative stress.
“Encouragingly however, a murine study has shown that N-acetyl-cysteine prevents thymocyte apoptosis and cell loss caused by exercise-induced oxidative stress (Quadrilatero and Hoffman-Goetz 2005).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Quadrilatero and Hoffman-Goetz 2005 source
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- Premisecitation
Antigen processing and presentation is impaired by oxidative stress.
“For example, antigen processing and presentation is impaired by oxidative stress (Martner et al. 2011; Preynat-Seauve et al. 2003)”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Martner et al. 2011 source
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- cites Preynat-Seauve et al. 2003
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- Interpretationreasoning
In the context of ageing, it is likely that the cumulative effect of behaviour over a substantial period of the lifespan influences the rate or degree of immunosenescence.
“In addition, it is likely that in the context of ageing, it is the cumulative effect of behaviour, over a substantial period of the lifespan, which influences the rate or degree of immunosenescence.”
Quote in the paperNot a substantial claim - Premisecitation
Strong links have been shown between antioxidant supplementation and T cell function at rest.
“Although strong links have been shown between antioxidant supplementation and T cell function at rest (Hoffmann et al. 2010; Malmberg et al. 2002; Marthandan et al. 2013, 2014)”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Hoffmann et al. 2010 source
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- cites Malmberg et al. 2002
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- cites Marthandan et al. 2013, 2014
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- Premisecitation
Optimal reactive oxygen species production is critical for cell function, especially immune cells.
“Optimal reactive oxygen species production is critical for cell function, especially immune cells”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
CMV reactivation occurs frequently in autoimmune conditions characterised by chronic redox imbalance.
“and CMV reactivation occurs frequently in autoimmune conditions characterised by chronic redox imbalance (Su et al. 2007).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Su et al. 2007
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- Interpretationcitation
Several lines of evidence suggest that oxidative stress is implicated in aspects of immunosenescence.
“In addition to the clear relationships between redox balance and exercise, several lines of evidence suggest that oxidative stress is implicated in aspects of immunosenescence.”
Quote in the paperSubstantial claim - Premisecitation
The levels of reactive oxygen species produced during moderate exercise bring about beneficial adaptations in a number of cell types.
“and the levels produced during moderate exercise have been proven to bring about beneficial adaptations in a number of cell types (Ji et al. 2006; Powers and Jackson 2008; Radak et al. 2008).”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationreasoning
The limited evidence to date for exercise preventing, delaying or restoring T cell immunosenescence suggests there is a U-shaped relationship with categories of exercise behaviour (sedentary, inactive, active, very active, and extremely active).
“The limited evidence to date for exercise preventing, delaying or restoring T cell immunosenescence suggests there is a U-shaped relationship with categories of exercise behaviour (e.g., sedentary, inactive, active, very active, and extremely active; see Fig. 1).”
Quote in the paperNot a substantial claim - Premisecitation
Healthy individuals infected with CMV exhibit elevated biomarkers of oxidative stress.
“Further, healthy individuals infected with CMV exhibit elevated biomarkers of oxidative stress (Lee et al. 2014)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Lee et al. 2014 source
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- Interpretationcitation
The evidence for dietary antioxidants modulating exercise-induced changes in T cell function is less clear.
“the evidence for dietary antioxidants modulating exercise-induced changes in T cell function is less clear.”
Quote in the paperSubstantial claim - Premisecitation
The 'oxidative footprint' of ultra-endurance exercise is detectable in some cells of the immune system for weeks, if not months.
“For example, the “oxidative footprint” of ultra-endurance exercise, is detectable in some cells of the immune system for weeks, if not months (Turner et al. 2011, 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Turner et al. 2011, 2013
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- May combine two claims. 44
- Classified as probably not a substantial claim. 29
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PremisecitationIf moderate-intensity exercise is undertaken regularly so that age-specific guidelines concerning duration and frequency are met, the result is a better functioning immune system and a lower incidence of disease.
“Moreover, if this form of exercise is undertaken regularly, so that age-specific guidelines concerning the recommended duration and frequency of exercise are met (e.g., 30 min of moderate intensity exercise on 5 days of the week for adults), the result is a better functioning immune system and a lower incidence of disease (Arem et al. 2015; Lee et al. 2012; World-Health-Organisation 2010).”
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PremisecitationHallmarks of immunosenescence measured in the T cell pool include low numbers and proportions of naïve cells, high numbers and proportions of late-stage differentiated effector memory cells, poor proliferative responses to mitogens, and a CD4:CD8 ratio <1.0.
“Hallmarks of immunosenescence measured in the T cell pool, include low numbers and proportions of naïve cells, high numbers and proportions of late-stage differentiated effector memory cells, poor proliferative responses to mitogens, and a CD4:CD8 ratio <1.0.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Wikby et al. 1994, 1998
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Pawelec 2012, 2013
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe effects of exercise on the immune system are well established.
“While the effects of exercise on the immune system are now well established (Walsh et al. 2011a,b) a more recent theme to emerge is whether exercise influences ageing of the immune system, also referred to as immunosenescence.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Walsh et al. 2011a,b
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PremisecitationA U- or J-shaped relationship between exercise and infection risk, inversely proportional to immune competence, has been proposed.
“Generally acute and chronic exercise is thought to be beneficial for immune function, however a U- or J-shaped relationship with infection risk, that is inversely proportional to immune competence, has been proposed (Gleeson and Walsh 2012; Walsh et al. 2011a, b).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Gleeson and Walsh 2012 source
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- cites Walsh et al. 2011a,b
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PremisecitationImmunosenescence is well characterised within the adaptive immune system, particularly among T cells.
“The age-associated decline in immune function, referred to as immunosenescence, is well characterised within the adaptive immune system, and in particular, among T cells.”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S4 (based).
Premisenone givenLymphocyte immune-surveillance is thought to be facilitated by the transient lymphocytosis and subsequent lymphocytopenia induced by exercise bouts.
“Further, lymphocyte immune-surveillance, whereby cells search tissues for antigens derived from viruses, bacteria, or malignant transformation, is thought to be facilitated by the transient lymphocytosis and subsequent lymphocytopenia induced by exercise bouts.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationCytomegalovirus infection has been directly linked with increased inflammatory activity, poor responses to vaccination, frailty, accelerated cognitive decline, and early mortality.
“These changes are largely driven by infection with Cytomegalovirus, which has been directly linked with increased inflammatory activity, poor responses to vaccination, frailty, accelerated cognitive decline, and early mortality.”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationLong-duration one-off bouts of exercise and weeks or months of very high-intensity long-duration athletic training are associated with an increased risk of certain infections, suggesting compromised immunity.
“Conversely, some evidence shows that long-duration one-off bouts of exercise (e.g., marathon running, especially if this is unaccustomed) and weeks or months of very high-intensity long-duration athletic training, sometimes referred to as “overreaching” or “over-training”, are associated with an increased risk of certain infections, suggesting compromised immunity (Bonini et al. 2015; Derman et al”
Quote in the paperSubstantial claim0 of 3 sources checkedClassified as probably not a substantial claim.
PremisecitationGenerally acute and chronic exercise is thought to be beneficial for immune function.
“Generally acute and chronic exercise is thought to be beneficial for immune function, however a U- or J-shaped relationship with infection risk, that is inversely proportional to immune competence, has been proposed (Gleeson and Walsh 2012; Walsh et al. 2011a, b).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Gleeson and Walsh 2012 source
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- cites Walsh et al. 2011a,b
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PremisecitationData from chronic exercise training interventions in the young and elderly show an anti-inflammatory effect of exercise, but long-term changes to immune cell function and phenotype are less consistent.
“Data from these studies in the young and elderly show an anti-inflammatory effect of exercise, but long-term changes to immune cell function and phenotype are less consistent (Gjevestad et al. 2015; Gleeson et al. 2011; Kohut and Senchina 2004; Simpson et al. 2012).”
Quote in the paperSubstantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductcitationWith chronic studies, measurements should be made 36-48 h after a final bout of exercise to avoid capturing changes induced by acute exercise.
“With chronic studies, measurements should be made 36–48 h after a final bout of exercise to avoid capturing changes induced by acute exercise (Thompson et al. 2010).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Thompson et al. 2010 source
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PremisecitationIndividuals can accumulate substantial sedentary time outside of regular structured exercise and therefore can be classified as being both 'active' and 'sedentary' at the same time.
“This is important because individuals can accumulate substantial sedentary time outside of regular structured exercise (Sedentary Behaviour Research 2012) and therefore counter-intuitively, can be classified as being both “active” and “sedentary” at the same time.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Sedentary Behaviour Research 2012 source
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Study design and conductcitationUsing precise and sensitive activity monitors might seem robust, but there are a number of considerations when interpreting this information.
“Although using precise and sensitive activity monitors might seem robust, there are a number of considerations when interpreting this information (Thompson and Batterham 2013; Thompson et al. 2009).”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationAgeing is associated with a lower number and altered tissue distribution of dendritic cells, which exhibit impaired antigen processing and presentation, along with decreased co-stimulatory and migratory capacity.
“Ageing is also associated with a lower number, and altered tissue distribution of dendritic cells, which exhibit impaired antigen processing and presentation, along with decreased co-stimulatory and migratory capacity (Panda et al. 2009).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Panda et al. 2009 source
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PremisecitationIt has been suggested that the number of natural regulatory T cells (nTREGs) increase with ageing whereas inducible regulatory T cells (iTREGs) decrease.
“In addition, attention has also turned to natural- and inducible- regulatory T cells (nTREG and iTREG respectively) and it has been suggested that the number of nTREGs increase with ageing whereas iTREGs decrease (Fessler et al. 2013; Jagger et al. 2014).”
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PremisecitationStudies examining CD4+ T-helper cells in the context of ageing have traditionally shown that cells exhibiting a Th2 profile dominate over cells with a Th1 profile in the elderly.
“Studies examining CD4+ T-helper (Th) cells in the context of ageing, have traditionally shown, based on their signature cytokine profiles, that cells exhibiting a Th2 profile (i.e., IL-4 producing cells) dominate over cells with a Th1 profile (i.e., IFN-γ producing cells) in the elderly (Deng et al. 2004; Shearer 1997).”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationAlthough the number of natural killer (NK) cells increases with age, cytokine production and cytotoxicity on a per cell basis decreases.
“Although the number of natural killer (NK) cells increases with age, cytokine production and cytotoxicity on a per cell basis decreases (Panda et al. 2009).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Panda et al. 2009 source
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PremisecitationAlterations to innate immunity with ageing include impaired phagocytosis and chemotaxis of neutrophils and monocytes/macrophages, with the latter exhibiting defective antigen processing and presentation, and an inflammatory phenotype.
“Alterations to innate immunity include impaired phagocytosis and chemotaxis of neutrophils and monocytes/macrophages, with the latter exhibiting defective antigen processing and presentation, and an inflammatory phenotype (Panda et al. 2009).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Panda et al. 2009 source
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PremisecitationMore recent focus has been on a possible accumulation of Th17 cells with age.
“However, more recent focus has been on a possible accumulation of Th17 cells with age (i.e., IL-17 producing cells that are associated with autoimmunity and inflammatory disease) (Schmitt et al. 2013).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Schmitt et al. 2013 source
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PremisecitationLate-stage differentiated effector memory CD4+ and CD8+ T cells accumulate with ageing and many are specific for latent Herpes viruses, especially Cytomegalovirus (CMV).
“Late-stage differentiated effector memory CD4+ and CD8+ T cells accumulate with ageing and many are specific for latent Herpes viruses, especially Cytomegalovirus (CMV) (van Lier et al. 2003).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites van Lier et al. 2003 source
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Study design and conductreasoningInterpretation of results from individual studies is dependent on critical methodological considerations.
“Although the summary above represents current thinking in exercise immunology, the interpretation of results from individual studies is dependent on critical methodological considerations.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationAgeing is associated with a decline in naïve B cell production, an accumulation of memory B cells with limited specificities, and less robust plasma cell responses to antigen, with the antibodies produced being less effective.
“As with T cells, ageing is associated with a decline in naïve B cell production, an accumulation of memory B cells with limited specificities, and less robust plasma cell responses to antigen, with the antibodies produced being less effective (Siegrist and Aspinall 2009).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Siegrist and Aspinall 2009 source
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PremisecitationAge-associated alterations in adaptive immunity are thought in part to be driven by an ageing haematopoietic stem cell niche and fewer circulating stem cells, which are characterised by intrinsic damage and a phenotype skewed towards the myeloid lineage.
“Age-associated alterations in adaptive immunity are thought in part, to be driven by an ageing haematopoietic stem cell niche and fewer circulating stem cells, which in turn, are characterised by intrinsic damage and a phenotype skewed towards the myeloid lineage (Geiger et al. 2013).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Geiger et al. 2013 source
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Study design and conductcitationMeasurements of lymphocyte function are strongly influenced by the numbers and proportions of cell types comprising the total lymphocyte pool at the time of sampling, highlighting the need for measurements to be made on a single-cell or single-phenotype basis.
“Further, measurements of lymphocyte function for example, are strongly influenced by the numbers and proportions of cell types comprising the total lymphocyte pool at the time of sampling, highlighting the need for measurements to be made on a single-cell or single-phenotype basis (Lavoy et al. 2013).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Lavoy et al. 2013 source
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PremisecitationVery few immune parameters are predictive of mortality and/or accepted as 'hallmarks' of an ageing immune system.
“Although many aspects of immune function change with ageing, and some of these alterations can be restored transiently by exercise, very few immune parameters are predictive of mortality and/or accepted as “hallmarks” of an ageing immune system (see next section) (Pawelec 2012, 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Pawelec 2012, 2013
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PremisecitationEarly studies indicated that the magnitude of T cell proliferative responses to mitogens in vitro is positively associated with survival in the elderly.
“Early studies indicated that the magnitude of T cell proliferative responses to mitogens in vitro is positively associated with survival in the elderly (Roberts-Thomson et al. 1974; Wayne et al. 1990).”
Quote in the paperNot a substantial claim0 of 2 sources checkedClassified as probably not a substantial claim. May combine two claims.
PremisecitationIL-7 might increase thymic mass and lead to the emergence of recent thymic emigrants.
“A post-exercise surge in thymopoiesis is possible considering that skeletal muscle secretes IL-7 (Haugen et al. 2010) which might in turn increase thymic mass and lead to the emergence of recent thymic emigrants (Fry and Mackall 2005).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Fry and Mackall 2005 source
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PremisecitationDespite inconsistent results over the effects of CMV on antibody responses to vaccination, studies consistently show that elderly individuals exhibiting other established hallmarks of an ageing immune system respond poorly to vaccines.
“Despite inconsistent results over the effects of CMV on antibody responses to vaccination, studies consistently show that elderly individuals, exhibiting other established hallmarks of an ageing immune system, respond poorly to vaccines (Haq and McElhaney 2014; Strindhall et al. 2016).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Haq and McElhaney 2014 source
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- cites Strindhall et al. 2016
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PremisecitationClassifying these cells as 'senescent' is subject to debate, and is dependent on what constitutes the definition of senescence.
“Classifying these cells as “senescent” however is subject to debate, and is dependent on what constitutes the definition of senescence (e.g., loss or expression of key cell-surface molecules, functional capacity, such as the ability to proliferate, produce cytokines and kill targets, or telomere length) (Koch et al. 2007; Pawelec 2013).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Koch et al. 2007 source
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- cites Pawelec 2013
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PremisecitationOther studies have reported vaccine-boosting effects of CMV in young individuals.
“For example, some studies have shown no effect of CMV on vaccine responses in the elderly (den Elzen et al. 2011; O’Connor et al. 2014; Wald et al. 2013) and other studies have even reported vaccine-boosting effects of CMV in young individuals (Furman et al. 2015).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Furman et al. 2015 source
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PremisecitationMany features of an ageing immune system appear to be driven by CMV, and infection with this virus alone has since been associated with frailty, cognitive impairment, poor responses to vaccination in young and elderly individuals, and ultimately earlier mortality.
“Indeed many features of an ageing immune system appear to be driven by CMV, and infection with this virus alone has since been associated with frailty (Haeseker et al. 2013), cognitive impairment (Gow et al. 2013), poor responses to vaccination in young and elderly individuals (Derhovanessian et al. 2012; Frasca et al. 2015; Moro-Garcia et al. 2012; Turner et al. 2014b; Wald et al. 2013), and”
Quote in the paperNot a substantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationLater work showed that IL-6 was also associated with frailty, cognitive decline and mortality.
“Later work showed that IL-6 was also associated with frailty, cognitive decline and mortality (Wikby et al. 2005, 2006).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Wikby et al. 2005, 2006
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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PremisecitationAccepted hallmarks of immunological ageing are low numbers and proportions of naïve T cells (in particular CD8+ T cells) and high numbers of memory T cells (especially late-stage differentiated CD8+ T cells).
“For example, accepted hallmarks of immunological ageing are low numbers and proportions of naïve T cells (in particular CD8+ T cells) and high numbers of memory T cells (especially late-stage differentiated CD8+ T cells) (Appay and Sauce 2014; Fulop et al. 2013; Pawelec 2012, 2013).”
Quote in the paperSubstantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationLarge inter-individual differences exist, and it has been reported that 23% of the CD8+ T cell pool can become specific for just a single CMV epitope.
“Large inter-individual differences exist, and it has been reported that 23 % of the CD8+ T cell pool can become specific for just a single CMV epitope (Khan et al. 2002).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Khan et al. 2002 source
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PremisecitationSome studies have shown no effect of CMV on vaccine responses in the elderly.
“For example, some studies have shown no effect of CMV on vaccine responses in the elderly (den Elzen et al. 2011; O’Connor et al. 2014; Wald et al. 2013) and other studies have even reported vaccine-boosting effects of CMV in young individuals (Furman et al. 2015).”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationcitationIt is currently unknown whether values such as 10% of the CD4+ and CD8+ T cell pool being specific for CMV is above, or below, the ideal threshold.
“It is therefore currently unknown whether values such as 10 % of the CD4+ and CD8+ T cell pool being specific for CMV is above, or below, the ideal threshold (Sylwester et al. 2005).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Sylwester et al. 2005 source
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PremisecitationA lower proportion of naïve CD8+ T cells, a higher proportion of memory CD8+ T cells, and a robust pro-inflammatory response to CMV, are associated with better survival in a longitudinal analysis of elderly individuals.
“For example, it has been shown that a lower proportion of naïve CD8+ T cells, a higher proportion of memory CD8+ T cells, and a robust pro-inflammatory response to CMV, are associated with better survival in a longitudinal analysis of elderly individuals (Derhovanessian et al. 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Derhovanessian et al. 2013 source
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InterpretationcitationFrom an evolutionary perspective, there may be an advantage to having an accumulation of late-stage differentiated T cells, assuming few are senescent/functionally exhausted, and considering that many will be specific for viruses such as CMV that require constant immune-surveillance.
“From an evolutionary perspective, there may be an advantage to having an accumulation of late-stage differentiated T cells, assuming few are senescent/functionally exhausted, and considering that many will be specific for viruses such as CMV that require constant immune-surveillance (van Lier et al. 2003).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites van Lier et al. 2003 source
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- The authors state this as an assumption: Few late-stage differentiated T cells are senescent/functionally exhausted.
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PremisecitationCells failing to proliferate can exhibit a profile that is distinct from replicative senescence, referred to as stress-induced premature senescence (SIPS).
“Indeed, cells failing to proliferate can exhibit a profile that is distinct from replicative senescence, referred to as stress-induced premature senescence (SIPS) (Toussaint et al. 2002a, b).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Toussaint et al. 2002a, b
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InterpretationreasoningProgrammed cell death is a balance between pro- and anti-apoptotic signals.
“These results, when interpreted with other data showing that CMV-specific cells exhibit high levels of the anti-apoptotic protein Bcl-2 (Khan et al. 2002), emphasise that programmed cell death is a balance between pro- and anti-apoptotic signals.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Khan et al. 2002 source
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Study design and conductcitationThis methodology is limited to common human leukocyte antigen (HLA)-types and is usually restricted to immunodominant antigens rather than the full spectrum of virus proteins that T cells target.
“However, this methodology is limited to common human leukocyte antigen (HLA)-types and is usually restricted to immunodominant antigens rather than the full spectrum of virus proteins that T cells target (Borchers et al. 2014).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Borchers et al. 2014 source
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PremisecitationAntioxidants Ebselen and N-acetyl-cysteine increase the lifespan and proliferative capacity of CD4+ T cell clones from healthy young and middle-aged donors, with increased GSH/GSSG ratio and lower oxidative DNA damage.
“Supplementing cultures with these antioxidants substantially increased the lifespan and proliferative capacity of T cell clones, which occurred in parallel with an increase in the ratio of reduced glutathione (GSH) to oxidised glutathione (GSSG) and lower oxidative DNA damage (Marthandan et al. 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Marthandan et al. 2013 source
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PremisecitationThe concept of a fixed amount of immunological space has been debated.
“Although a decline in thymic output with ageing is accepted, the concept of a fixed amount of immunological space has been debated (Huster et al. 2009; Schwanninger et al. 2007; van Leeuwen et al. 2006; Vezys et al. 2009).”
Quote in the paperNot a substantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationCMV-specific CD8+ T cells in peripheral blood exhibit high levels of anti-apoptotic protein Bcl-2, which might render them insensitive to Fas-induced cell death.
“CMV-specific CD8+ T cells measured in peripheral blood have been shown to exhibit high levels of the anti-apoptotic protein Bcl-2 (Khan et al. 2002), which might render them insensitive to cell death induced the Fas-receptor (Fas-R) interacting with Fas-ligand (Fas-L).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Khan et al. 2002 source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationSenescent CD8+ T cells are resistant to apoptosis based on in vitro experiments.
“on the basis of in vitro experiments, it is commonly cited that “senescent” CD8+ T cells are resistant to apoptosis (Spaulding et al. 1999).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Spaulding et al. 1999 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationSIPS is brought about by exposure to sub-cytotoxic stress (e.g., by reactive oxygen species) and is characterised by growth arrest and adoption of a senescence-associated secretory phenotype, whereby inflammatory cytokines and transforming growth factor-beta (TGF-β) are produced.
“This state, brought about by exposure to sub-cytotoxic stress (e.g., by reactive oxygen species) is characterised by growth arrest and adoption of a senescence-associated secretory phenotype, whereby inflammatory cytokines and transforming growth factor-beta (TGF-β) are produced (Toussaint et al. 2002a, b).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Toussaint et al. 2002a, b
Not checked in the free run.
Classified as probably not a substantial claim.
InterpretationreasoningRather than 'senescence' per se, the higher cumulative IFN-γ production might reflect a mechanism to limit excessive inflammatory activity when controlling CMV in the elderly.
“Rather than “senescence” per se, this might reflect a mechanism to limit excessive inflammatory activity when controlling CMV in the elderly.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationnone givenExercise recommendations are exceeded by elite athletes and extreme exercisers, and this may be associated with immune deregulation.
“are exceeded by elite athletes and extreme exercisers (the latter include individuals taking part in ultra-endurance training and competition) and this may be associated with immune deregulation.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationUntrained individuals exhibited the highest proportions of CD4+ and CD8+ late-stage differentiated cells and the lowest proportions of CD8+ naive cells.
“Supporting an anti-immunosenescence effect of exercise, untrained individuals exhibited the highest proportions of CD4+ and CD8+ late-stage differentiated cells, and the lowest proportions of CD8+ naïve cells (Brown et al. 2014).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Brown et al. 2014 source
Not checked in the free run.
May combine two claims.
InterpretationreasoningSimilar characteristics of immunosenescence are present at each extreme of the exercise-continuum, but the magnitude of effect and origin of immune deregulation differ between sedentary/inactive and elite/extreme exercisers.
“Similar characteristics of immunosenescence are present at each extreme of the exercise-continuum, but the magnitude of effect, and origin of immune deregulation, potentially mediated by inflammation and oxidative stress, is different”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationFitter individuals exhibit a smaller age-associated decline in naive T cells and a smaller accumulation of late-stage differentiated T cells.
“Thus, it was concluded that fitter individuals exhibit a smaller age-associated decline in naïve T cells and a smaller accumulation of late-stage differentiated T cells.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Spielmann et al. 2011 source
Not checked in the free run.
May combine two claims.
InterpretationcitationCMV reactivation might be more frequent in obesity because excess adiposity drives chronic systemic inflammation and oxidative stress, which can reactivate CMV directly.
“CMV reactivation might be even more frequent in obesity, because excess adiposity drives chronic systemic inflammation and oxidative stress (Aroor and DeMarco 2014; Cervellati et al. 2014; de Heredia et al. 2012; Kanneganti and Dixit 2012; Le Lay and Simard 2014), which in turn can reactivate CMV directly (Cinatl et al. 1999; Docke et al. 1994; Jaganjac et al. 2010; Prosch et al. 1995; Speir 2000;”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationFollowing kidney transplant, CMV-specific T cells appeared and expanded substantially, acquiring differentiated profiles, while absolute numbers of pre-existing EBV-specific and Influenza-specific T cells remained stable.
“By analysing the numbers, proportions and phenotype of cells, an appearance of CMV-specific T cells was shown following kidney transplant, and these cells expanded substantially, acquiring differentiated profiles. However, the absolute number of pre-existing EBV-specific and Influenza-specific T cells remained stable (van Leeuwen et al. 2006).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites van Leeuwen et al. 2006 source
Not checked in the free run.
May combine two claims.
InterpretationreasoningExercise might reduce viral reactivation in lean, overweight and obese individuals by decreasing adiposity and maintaining redox balance, limiting accumulation of late-stage differentiated CMV-specific T cells.
“considering exercise decreases visceral and subcutaneous adiposity even in the absence of “weight loss” (Ross and Janiszewski 2008; Tchernof and Despres 2013), and exercise is a potent anti-inflammatory stimulus that helps maintain redox balance even in obesity (Farinha et al. 2015; Gleeson et al. 2011; Ji et al. 2006; Radak et al. 2008), then exercise might reduce viral reactivation in lean,”
Quote in the paperSubstantial claim0 of 3 sources checkedClassified as probably not a substantial claim.
PremisecitationIt is commonly cited that there is a linear relationship between reactive oxygen species production and the volume and intensity of exercise.
“It is commonly cited that there is a linear relationship between reactive oxygen species production and the volume and intensity of exercise (Finaud et al. 2006).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Finaud et al. 2006 source
Not checked in the free run.
May combine two claims.
InterpretationreasoningThe relationship between the volume of exercise and the rate or degree of immunosenescence is probably not linear, and is likely strongly influenced by lifetime accumulation of exercise behaviour.
“the relationship between the volume of exercise and the rate or degree of immunosenescence is probably not linear, and is likely to be strongly influenced by a lifetime accumulation of exercise behaviour (see Fig. 1).”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationRegular moderate-intensity exercise stimulates optimal reactive oxygen species production above resting values, but not to the levels associated with chronic sedentary behaviour.
“Regular moderate-intensity exercise stimulates optimal reactive oxygen species production above resting values, but not to the levels associated with chronic sedentary behaviour (Bjork et al. 2012; Derbre et al. 2014; Gratas-Delamarche et al. 2014; Le Lay and Simard 2014).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
InterpretationcitationThe age-associated decrease in naive T cells and increase in late-stage differentiated T cells did not withstand statistical adjustment for cardiorespiratory fitness, suggesting ageing may be secondary to fitness in shaping the T cell repertoire.
“Fascinatingly, the age-associated decrease in the proportion of naïve T cells and increase in the proportion of late-stage differentiated T cells, did not withstand statistical adjustment for cardiorespiratory fitness, suggesting that ageing may be secondary to fitness in shaping the T cell repertoire.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Spielmann et al. 2011 source
Not checked in the free run.
May combine two claims.
InterpretationcitationA pro-immunosenescence effect of high-volume exercise might only be apparent in younger adults, and is no worse than immune decline caused by chronological ageing and/or infection history.
“This finding suggests that a pro-immunosenescence effect of high-volume exercise might only be apparent in younger adults, and this effect is no worse than the immune decline caused by chronological ageing and/or infection history itself.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Moro-Garcia et al. 2014 source
Not checked in the free run.
May combine two claims.
PremisecitationEndurance athletes in the third decade exhibited a greater proportion of late-stage differentiated CD4+ (but not CD8+) T cells, a lower CD4:CD8 ratio, poor T cell activation to anti-CD3, and reduced thymic output of CD8+ T cells compared to less-active age-matched controls.
“endurance athletes in the third decade of life (n = 27) exhibited a greater proportion of late-stage differentiated CD4+ (but not CD8+) T cells, a lower CD4:CD8 ratio, poor T cell activation in response to anti-CD3 stimulation, and reduced thymic output of CD8+ T cells, as shown by T cell receptor excision circle (TREC) quantification, compared to less-active age-matched controls (n = 30) (Moro-G”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Moro-Garcia et al. 2014 source
Not checked in the free run.
May combine two claims.
PremisecitationSeveral other studies have reported that dietary antioxidants do not affect the typical changes in lymphocyte function induced by acute exercise, but many of these studies have examined non-specific aspects of cell-mediated immunity.
“Several other studies have reported that dietary antioxidants do not affect the typical changes in lymphocyte function induced by acute exercise, but many of these studies have examined non-specific aspects of cell-mediated immunity (McAnulty et al. 2011; Petersen et al. 2001).”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationIf antioxidant molecules are depleted in T cells, cytokine production can become uncontrolled, potentially resulting in an inflammatory environment that is known to reactivate CMV.
“Finally, if antioxidant molecules are depleted in T cells, then cytokine production, can become uncontrolled (Michalek et al. 2012), potentially resulting in an inflammatory environment that is also known to reactivate CMV (Docke et al. 1994; Prosch et al. 1995; Stein et al. 1993).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationHigh levels of reactive oxygen species in T cells impair cytotoxicity, perhaps mediated by T cell lipid peroxidation, resulting in failure to control viruses.
“and high levels of reactive oxygen species in T cells impair cytotoxicity, perhaps mediated by T cell lipid peroxidation, resulting in failure to control viruses (Henson et al. 2014; Matsushita et al. 2015).”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S4 (based). May combine two claims.
InterpretationreasoningSome forms of exercise might prevent and/or delay immunosenescence, perhaps even restoring immunosenescent profiles.
“it is appealing that some forms of exercise might prevent and/or delay immunosenescence, perhaps even restoring immunosenescent profiles.”
Quote in the paperNot a substantial claim- Rests on an assumption: Ageing results in deleterious alterations to innate and adaptive immunity.
- Rests on an assumption: Exercise is a powerful stimulus of immune function.
Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
InterpretationreasoningA possible anti-immunosenescence effect of exercise could also be elicited indirectly (e.g., better anti-viral control, mediated by redox balance and less inflammatory activity, possibly linked to adipose tissue regulation).
“However, a possible anti-immunosenescence effect of exercise could also be elicited indirectly (e.g., better anti-viral control, mediated by redox balance and less inflammatory activity, possibly linked to adipose tissue regulation).”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationReactive oxygen species and 4-hydroxy-2-nonenal (HNE) can directly reactivate CMV, but this process can be inhibited by antioxidants.
“Mechanistic studies show that reactive oxygen species and one of the final products of lipid peroxidation, 4-hydroxy-2-nonenal (HNE), can directly reactivate CMV, but this process can be inhibited by antioxidants (Cinatl et al. 1999; Jaganjac et al. 2010; Speir 2000; Vossen et al. 1997).”
Quote in the paperSubstantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningOxidative stress might promote CMV reactivation indirectly, because redox balance is intricately involved in cell-mediated immunity.
“Finally, oxidative stress might promote CMV reactivation indirectly, considering that redox balance is intricately involved in cell-mediated immunity.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationSelf-reported illness symptoms following a period of demanding exercise training are lower in athletes supplementing their diet with Quercetin, but this antioxidant had no effect on assessments of immune function before and after acute exercise.
“For example, although self-reported illness symptoms following a period of demanding exercise training have been shown to be lower in athletes supplementing their diet with Quercetin, this antioxidant had no effect on assessments immune function before and after acute exercise (Nieman et al. 2007).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Nieman et al. 2007 source
Not checked in the free run.
The authors state this as an assumption.
Few late-stage differentiated T cells are senescent/functionally exhausted.
“assuming few are senescent/functionally exhausted”
The authors state this as an assumption.
A negative feedback loop governs the number of naïve and memory cells.
“hypothetical negative feedback loop that governs the number of naïve and memory cells”
The authors state this as an assumption.
Exercise invokes anti-immunosenescence effects, in part by limiting the expansion of CMV-specific late-stage differentiated T cells.
“Assuming exercise invokes anti-immunosenescence effects, in part by limiting the expansion of CMV-specific late-stage differentiated T cells, it could be that these changes are brought about indirectly, as opposed to the mechanisms (i.e., deletion and replacement of cells) proposed in the “exercise makes immunological space” hypothesis.”
The authors state this as an assumption.
There is a post-exercise production of naïve cells.
“Assuming there is a post-exercise production of naïve cells, a key question is whether thymopoeisis, extrathymic T cell development, or a combination of the two is responsible.”
The paper relies on this without support.
Ageing results in deleterious alterations to innate and adaptive immunity.
“Considering that ageing results in deleterious alterations to innate and adaptive immunity”
The paper relies on this without support.
Exercise is a powerful stimulus of immune function.
“and that exercise is a powerful stimulus of immune function”
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?
Several factors, such as genetics, nutrition, exercise, previous exposure to microorganisms, biological and cultural sex, and HCMV status, can influence immunosenescence.
“Several factors, such as genetics, nutrition, exercise, previous exposure to microorganisms, biological and cultural sex, and human cytomegalovirus (HCMV) status can influence immunosenescence (3, 6–11).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [10]
The main barrier to better clarity remains the wide heterogeneity among human beings, linked to different life-style and genetic factors that influence the rate of immunosenescence.
“The main barrier to better clarity remains the wide heterogeneity among human beings, linked to different life-style and genetic factors that influence the rate of immunosenescence (6, 10, 11, 82).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [10]
The citation lists haven’t been fetched yet
References 214 · Cited by 112
- Authors
- Turner, J. E.
- Affiliations
- University of Bath (GB)
- Corresponding author
- Turner, James E.
- Venue
- Biogerontology
- Published
- 2016-03-29
- Volume
- 17
- Issue
- 3
- Pages
- 581-602
- ISSN
- 1389-5729 (ISSN-L)
- 1573-6768
- PMC
- PMC4889625
- OpenAlex
- W2298103958
- Semantic Scholar
- cbf2286dbc71283a2be40f62816b482a53ba0c13
- Cited by
- 112
- References
- 214
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 10 · 2023: 15 · 2022: 5 · 2021: 18 · 2020: 16 · 2019: 11 · 2018: 12 · 2017: 6 · 2016: 6
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Update notices
- correction (2016-05-17)
- Open access
- hybrid
- doi.org
- Locations
- Biogerontology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Topics
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- immunosenescence, physical activity, T cells, cytomegalovirus infection, CD4/CD8 ratio, naive T cells, effector memory T cells, vaccine response, lymphocytosis, lymphopenia, anti-inflammatory effects of exercise, immune rejuvenation
- MeSH terms
- Immunosenescence, Exercise Therapy, Physical Exertion, Humans, Immunity, Innate, T-Lymphocytes, Exercise, Treatment Outcome, Models, Immunological, Evidence-Based Medicine, Sarcopenia
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