scholarly journals Age-related declines in immune response in a wild mammal are unrelated to immune cell telomere length

2016 ◽  
Vol 283 (1825) ◽  
pp. 20152949 ◽  
Author(s):  
Christopher Beirne ◽  
Laura Waring ◽  
Robbie A. McDonald ◽  
Richard Delahay ◽  
Andrew Young
Keyword(s):  
Telomere Length ◽  
Individual Variation ◽  
Immune Cell ◽  
Ex Vivo ◽  
Natural Populations ◽  
Population Level ◽  
Meles Meles ◽  
Wild Mammal ◽  
Age Related ◽  
Age Variation

Senescence has been hypothesized to arise in part from age-related declines in immune performance, but the patterns and drivers of within-individual age-related changes in immunity remain virtually unexplored in natural populations. Here, using a long-term epidemiological study of wild European badgers ( Meles meles ), we (i) present evidence of a within-individual age-related decline in the response of a key immune-signalling cytokine, interferon-gamma (IFN γ ), to ex vivo lymphocyte stimulation, and (ii) investigate three putative drivers of individual variation in the rate of this decline (sex, disease and immune cell telomere length; ICTL). That the within-individual rate of age-related decline markedly exceeded that at the population level suggests that individuals with weaker IFN γ responses are selectively lost from this population. IFN γ responses appeared to decrease with the progression of bovine tuberculosis infection (independent of age) and were weaker among males than females. However, neither sex nor disease influenced the rate of age-related decline in IFN γ response. Similarly, while ICTL also declines with age, variation in ICTL predicted neither among- nor within-individual variation in IFN γ response. Our findings provide evidence of within-individual age-related declines in immune performance in a wild mammal and highlight the likely complexity of the mechanisms that generate them.

scholarly journals Inflamm-Aging Is Associated with Lower Plasma PTX3 Concentrations and an Impaired Capacity of PBMCs to Express hTERT following LPS Stimulation

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Aaron L. Slusher ◽  
Tiffany M. Zúñiga ◽  
Edmund O. Acevedo
Keyword(s):  
Gene Expression ◽  
Young Adults ◽  
Telomere Length ◽  
Immune Cell ◽  
Ex Vivo ◽  
Middle Aged ◽  
Human Telomerase Reverse Transcriptase ◽  
Negatively Associated ◽  
Htert Gene ◽  
Age Related

Age-related elevations in proinflammatory cytokines, known as inflamm-aging, are associated with shorter immune cell telomere lengths. Purpose. This study examined the relationship of plasma PTX3 concentrations, a biomarker of appropriate immune function, with telomere length in 15 middle-aged (40-64 years) and 15 young adults (20-31 years). In addition, PBMCs were isolated from middle-aged and young adults to examine their capacity to express a key mechanistic component of telomere length maintenance, human telomerase reverse transcriptase (hTERT), following ex vivo cellular stimulation. Methods. Plasma PTX3 and inflammatory cytokines (i.e., IL-6, IL-10, TGF-β, and TNF-α), PBMC telomere lengths, and PBMC hTERT gene expression and inflammatory protein secretion following exposure to LPS, PTX3, and PTX3+LPS were measured. Results. Aging was accompanied by the accumulation of centrally located visceral adipose tissue, without changes in body weight and BMI, and alterations in the systemic inflammatory milieu (decreased plasma PTX3 and TGF-β; increased TNF-α (p≤0.050)). In addition, shorter telomere lengths in middle-aged compared to young adults (p=0.011) were negatively associated with age, body fat percentages, and plasma TNF-α (r=−0.404, p=0.027; r=−0.427, p=0.019; and r=−0.323, p=0.041, respectively). Finally, the capacity of PBMCs to increase hTERT gene expression following ex vivo stimulation was impaired in middle-aged compared to young adults (p=0.033) and negatively associated with telomere lengths (r=0.353, p=0.028). Conclusions. Proinflammation and the impaired hTERT gene expression capacity of PBMCs may contribute to age-related telomere attrition and disease.

scholarly journals Estimation of environmental and genetic contributions to telomere length variation in a wild mammal

2020 ◽  
Author(s):  
Sil H. J. van Lieshout ◽  
Alex Sparks ◽  
Amanda Bretman ◽  
Chris Newman ◽  
Christina D. Buesching ◽  
...  
Keyword(s):  
Telomere Length ◽  
Individual Variation ◽  
Evolutionary Dynamics ◽  
Meles Meles ◽  
Length Variation ◽  
Phenotypic Variance ◽  
Parental Age ◽  
Transgenerational Effects ◽  
Wild Mammal ◽  
Relative Contribution

Understanding individual variation in fitness-related traits requires separating the environmental and genetic determinants. Telomeres are protective caps at the ends of chromosomes that are thought to be a biomarker of senescence as their length predicts mortality risk and reflect the physiological consequences of environmental conditions. The relative contribution of genetic and environmental factors to individual variation in telomere length is however unclear, yet important for understanding its evolutionary dynamics. In particular, the evidence for transgenerational effects, in terms of parental age at conception, on telomere length is mixed. Here, we investigate the heritability of telomere length, using the ‘animal model’, and parental age at conception effects on offspring telomere length in a wild population of European badgers (Meles meles). While we found no heritability of telomere length, our power to detect heritability was low and a repeatability of 2% across individual lifetimes provides a low upper limit to ordinary heritability. However, year (25%) and cohort (3%) explained greater proportions of the phenotypic variance in telomere length. There was no support for parental age at conception effects, or for longitudinal within-parental age effects on offspring telomere length. Our results indicate a lack of transgenerational effects through parental age at conception and a low potential for evolutionary change in telomere length in this population. Instead, we provide evidence that individual variation in telomere length is largely driven by environmental variation in this wild mammal.

scholarly journals Social effects on age-related and sex-specific immune cell profiles in a wild mammal

2019 ◽  
Author(s):  
Sil H. J. van Lieshout ◽  
Elisa Perez Badas ◽  
Michael W.T. Mason ◽  
Chris Newman ◽  
Christina D. Buesching ◽  
...  
Keyword(s):  
Immune Responses ◽  
Social Environment ◽  
Immune Cell ◽  
Meles Meles ◽  
Wild Mammal ◽  
Age Related ◽  
In The Wild ◽  
The Individual ◽  
The Impact ◽  
Age Related Changes

Evidence for age-related changes in innate and adaptive immune responses is increasing in wild populations. Such changes have been linked to fitness, and understanding the factors driving variation in immune responses is important for the evolution of immunity and senescence. Age-related changes in immune profiles may be due to sex-specific behaviour, physiology and responses to environmental conditions. Social conditions may also contribute to variation in immunological responses, for example, through transmission of pathogens and stress from resource and mate competition. Yet, the impact of the social environment on age-related changes in immune cell profile requires further investigation in the wild. Here, we tested the relationship between leukocyte cell composition (agranulocyte proportion, i.e. adaptive and innate immunity) and age, sex, and group size in a wild population of European badgers (Meles meles). We found that the proportion of agranulocytes decreased with age only in males living in small groups. In contrast, females in larger groups exhibited a greater age-related decline in the proportion of agranulocytes compared to females in smaller groups. Our results provide evidence for age-related changes in immune cell profiles in a wild mammal, which are influenced by both the sex of the individual and their social environment.

scholarly journals Age-Related Declines and Disease-Associated Variation in Immune Cell Telomere Length in a Wild Mammal

PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e108964 ◽  
Author(s):  
Christopher Beirne ◽  
Richard Delahay ◽  
Michelle Hares ◽  
Andrew Young
Keyword(s):  
Telomere Length ◽  
Immune Cell ◽  
Wild Mammal ◽  
Age Related

scholarly journals Incidence and severity of G6PI-induced arthritis are not increased in genetically distinct mouse strains upon aging

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Nico Andreas ◽  
Sylvia Müller ◽  
Nicole Templin ◽  
Paul M. Jordan ◽  
Harald Schuhwerk ◽  
...  
Keyword(s):  
Immune Cell ◽  
Ex Vivo ◽  
Wild Type Mouse ◽  
Mouse Strains ◽  
Functional Difference ◽  
Susceptible Mouse ◽  
Age Related ◽  
Th Cell ◽  
Old Mice

Abstract Background The incidence of rheumatoid arthritis is correlated with age. In this study, we analyzed the association of the incidence and severity of glucose-6-phosphate isomerase (G6PI)-induced arthritis with age in two different mouse strains. Methods Young and very old mice from two different arthritis-susceptible wild-type mouse strains were analyzed after a single subcutaneous injection of G6PI s.c. The metabolism and the function of synoviocytes were analyzed in vitro, the production of bioactive lipid mediators by myeloid cells and synoviocytes was assessed in vitro and ex vivo by UPLC-MS-MS, and flow cytometry was used to verify age-related changes of immune cell composition and function. Results While the severity of arthritis was independent from age, the onset was delayed in old mice. Old mice showed common signs of immune aging like thymic atrophy associated with decreased CD4+ effector T cell numbers. Despite its decrease, the effector T helper (Th) cell compartment in old mice was reactive and functionally intact, and their Tregs exhibited unaltered suppressive capacities. In homeostasis, macrophages and synoviocytes from old mice produced higher amounts of pro-inflammatory cyclooxygenase (COX)-derived products. However, this functional difference did not remain upon challenge in vitro nor upon arthritis reactions ex vivo. Conclusion While old mice show a higher baseline of inflammatory functions, this does not result in increased reaction towards self-antigens in arthritis-susceptible mouse strains. Together, our data from two different mouse strains show that the susceptibility for G6PI-induced arthritis is not age-dependent.

scholarly journals METABOLIC FLEXIBILITY IN CLASSICAL MONOCYTES IS NOT AFFECTED BY AGE

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S105-S105
Author(s):  
Johnathan Yarbro ◽  
Brandt Pence
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Immune Cell ◽  
Ex Vivo ◽  
Inflammatory Cells ◽  
Acid Oxidation ◽  
Low Grade ◽  
Glucose Starvation ◽  
Cell Functions ◽  
Age Related

Abstract Inflammaging is the chronic low-grade inflammation that occurs with age that contributes to the pathology of age-related diseases. Monocytes are innate immune cells that become dysregulated with age and which can contribute to inflammaging. Metabolism plays a key role in determining immune cell functions, with anti-inflammatory cells primarily relying on fatty acid oxidation and pro-inflammatory cells primarily relying on glycolysis. It was recently shown that lipopolysaccharide (LPS)-stimulated monocytes can compensate for a lack of glucose by utilizing fatty acid oxidation. Given that mitochondrial function decreases with age, we hypothesized that monocytes taken from aged individuals would have an impaired ability to upregulate oxidative metabolism and would have impaired effector functions. Aging did not impair LPS-induced oxygen consumption rate during glucose starvation as measured on a Seahorse XFp system. Additionally, aged monocytes maintained inflammatory gene expression responses and phagocytic capacity during LPS stimulation in the absence of glucose. In conclusion, aged monocytes maintain effector and metabolic functions during glucose starvation, at least in an ex vivo context.

scholarly journals Early-life telomere length predicts survival to adulthood and lifespan in a wild mammal

2018 ◽  
Author(s):  
Sil H. J. van Lieshout ◽  
Amanda Bretman ◽  
Chris Newman ◽  
Christina D. Buesching ◽  
David W. Macdonald ◽  
...  
Keyword(s):  
Telomere Length ◽  
Early Life ◽  
Meles Meles ◽  
Rate Of Change ◽  
Wild Mammal ◽  
Cross Sectional ◽  
Early Life Conditions ◽  
Individual Consistency ◽  
And Function ◽  
European Badgers

Telomeres, protective caps at the end of chromosomes, maintain genomic stability and function as a biomarker of senescence in many vertebrate species. Telomere length at different ages has been related to (subsequent) lifespan, but to date only one laboratory-based study has shown a direct link between early-life telomere length and lifespan. Whether this relationship holds in wild populations, where individuals are subject to variable natural conditions that may mask relationships seen in controlled laboratory settings, remains unknown. Here, we provide evidence that early-life telomere length predicts survival to adulthood in a wild population of European badgers (Meles meles). Furthermore, both early-life telomere length and telomere rate of change predict lifespan. We found a complex cross-sectional relationship between telomere length and age, where telomeres shortened over the first 38 months, but with no uniform loss after this point. We found little within-individual consistency in telomere length across lifespan, where telomere length did not predict residual lifespan. Importantly, we also observed increases in mean telomere length within individuals, which could not be explained by measurement error alone. Early-life telomere length varied distinctly among cohorts, indicating a role for early-life environment and additive genetic effects. Our results elaborate on the dynamic way that telomeres function as a biomarker of senescence in a wild mammal, where telomere length and rate of change can reflect short-term and lasting effects of early-life conditions on individual life-history.

scholarly journals Social effects on age-related and sex-specific immune cell profiles in a wild mammal

2020 ◽  
Vol 16 (7) ◽  
pp. 20200234 ◽  
Author(s):  
Sil H. J. van Lieshout ◽  
Elisa P. Badás ◽  
Michael W. T. Mason ◽  
Chris Newman ◽  
Christina D. Buesching ◽  
...  
Keyword(s):  
Social Environment ◽  
Group Size ◽  
Immune Cell ◽  
System Development ◽  
Wild Mammal ◽  
Age Related ◽  
Immune System Development ◽  
The Social ◽  
The Impact ◽  
Age Related Changes

Evidence for age-related changes in innate and adaptive immune responses is increasing in wild populations. Such changes have been linked to fitness, and knowledge of the factors driving immune response variation is important for understanding the evolution of immunity. Age-related changes in immune profiles may be owing to factors such as immune system development, sex-specific behaviour and responses to environmental conditions. Social environments may also contribute to variation in immunological responses, for example, through transmission of pathogens and stress arising from resource and mate competition. Yet, the impact of the social environment on age-related changes in immune cell profiles is currently understudied in the wild. Here, we tested the relationship between leukocyte cell composition (proportion of neutrophils and lymphocytes [innate and adaptive immunity, respectively] that were lymphocytes) and age, sex and group size in a wild population of European badgers ( Meles meles ). We found that the proportion of lymphocytes in early life was greater in males in smaller groups compared to larger groups, but with a faster age-related decline in smaller groups. By contrast, the proportion of lymphocytes in females was not significantly related to age or group size. Our results provide evidence of sex-specific age-related changes in immune cell profiles in a wild mammal, which are influenced by the social environment.

scholarly journals Individual variation in early‐life telomere length and survival in a wild mammal

2019 ◽  
Vol 28 (18) ◽  
pp. 4152-4165 ◽  
Author(s):  
Sil H. J. Lieshout ◽  
Amanda Bretman ◽  
Chris Newman ◽  
Christina D. Buesching ◽  
David W. Macdonald ◽  
...  
Keyword(s):  
Telomere Length ◽  
Individual Variation ◽  
Early Life ◽  
Wild Mammal

scholarly journals Monocytes from Older Adults Maintain Capacity for Metabolic Compensation during Glucose Deprivation and Lipopolysaccharide Stimulation

2019 ◽  
Author(s):  
Johnathan R. Yarbro ◽  
Brandt D. Pence
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Immune Cell ◽  
Ex Vivo ◽  
Glucose Deprivation ◽  
Inflammatory Cells ◽  
Acid Oxidation ◽  
Low Grade ◽  
Cell Functions ◽  
Age Related

ABSTRACTInflammaging is the chronic low-grade inflammation that occurs with age that contributes to the pathology of age-related diseases. Monocytes are innate immune cells that become dysregulated with age and which can contribute to inflammaging. Metabolism plays a key role in determining immune cell functions, with anti-inflammatory cells primarily relying on fatty acid oxidation and pro-inflammatory cells primarily relying on glycolysis. It was recently shown that lipopolysaccharide (LPS)-stimulated monocytes can compensate for a lack of glucose by utilizing fatty acid oxidation. Given that mitochondrial function decreases with age, we hypothesized that monocytes taken from aged individuals would have an impaired ability to upregulate oxidative metabolism along with impaired effector functions. Aging did not impair LPS-induced oxygen consumption rate during glucose deprivation as measured on a Seahorse XFp system. Additionally, aged monocytes maintained inflammatory gene expression responses and phagocytic capacity during LPS stimulation in the absence of glucose. In conclusion, aged monocytes maintain effector and metabolic functions during glucose deprivation, at least in an ex vivo context.

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