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

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.

Download Full-text

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

Mediators of Inflammation ◽

10.1155/2019/2324193 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 1

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.

Download Full-text

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

10.32942/osf.io/ezgxd ◽

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.

Download Full-text

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

Biology Letters ◽

10.1098/rsbl.2020.0234 ◽

2020 ◽

Vol 16 (7) ◽

pp. 20200234 ◽

Cited By ~ 1

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.

Download Full-text

TERRA: A Novel Biomarker of Embryo Quality and Art Outcome

Genes ◽

10.3390/genes12040475 ◽

2021 ◽

Vol 12 (4) ◽

pp. 475

Author(s):

Maria Santa Rocca ◽

Ludovica Dusi ◽

Andrea Di Nisio ◽

Erminia Alviggi ◽

Benedetta Iussig ◽

...

Keyword(s):

Telomere Length ◽

Dna Sequences ◽

Male Fertility ◽

Embryo Quality ◽

Assisted Reproductive Technologies ◽

Biological Clock ◽

Reproductive Technologies ◽

Age Related ◽

Non Coding Rna ◽

First Time

Telomeres are considered to be an internal biological clock, and their progressive shortening has been associated with the risk of age-related diseases and reproductive alterations. Over recent years, an increasing number of studies have focused on the association between telomere length and fertility, identifying sperm telomere length (STL) as a novel biomarker of male fertility. Although typically considered to be repeated DNA sequences, telomeres have recently been shown to also include a long non-coding RNA (lncRNA) known as TERRA (telomeric repeat-containing RNAs). Interestingly, males with idiopathic infertility show reduced testicular TERRA expression, suggesting a link between TERRA and male fertility. The aim of this study was to investigate the role of seminal TERRA expression in embryo quality. To this end, STL and TERRA expression were quantified by Real Time qPCR in the semen of 35 men who underwent assisted reproductive technologies (ART) and 30 fertile men. We found that TERRA expression in semen and STL was reduced in patients that underwent ART (both p < 0.001). Interestingly, TERRA and STL expressions were positively correlated (p = 0.010), and TERRA expression was positively associated with embryo quality (p < 0.001). These preliminary findings suggest a role for TERRA in the maintenance of sperm telomere integrity during gametogenesis, and for the first time, TERRA expression was found as a predictive factor for embryo quality in the setting of assisted reproduction.

Download Full-text

Telomere Length and Oxidative Stress and Its Relation with Metabolic Syndrome Components in the Aging

Biology ◽

10.3390/biology10040253 ◽

2021 ◽

Vol 10 (4) ◽

pp. 253

Author(s):

Graciela Gavia-García ◽

Juana Rosado-Pérez ◽

Taide Laurita Arista-Ugalde ◽

Itzen Aguiñiga-Sánchez ◽

Edelmiro Santiago-Osorio ◽

...

Keyword(s):

Oxidative Stress ◽

Metabolic Syndrome ◽

Telomere Length ◽

Scientific Evidence ◽

Telomeric Dna ◽

Biochemical Alterations ◽

The Metabolic Syndrome ◽

Age Related ◽

And Function

A great amount of scientific evidence supports that Oxidative Stress (OxS) can contribute to telomeric attrition and also plays an important role in the development of certain age-related diseases, among them the metabolic syndrome (MetS), which is characterised by clinical and biochemical alterations such as obesity, dyslipidaemia, arterial hypertension, hyperglycaemia, and insulin resistance, all of which are considered as risk factors for type 2 diabetes mellitus (T2DM) and cardiovascular diseases, which are associated in turn with an increase of OxS. In this sense, we review scientific evidence that supports the association between OxS with telomere length (TL) dynamics and the relationship with MetS components in aging. It was analysed whether each MetS component affects the telomere length separately or if they all affect it together. Likewise, this review provides a summary of the structure and function of telomeres and telomerase, the mechanisms of telomeric DNA repair, how telomere length may influence the fate of cells or be linked to inflammation and the development of age-related diseases, and finally, how the lifestyles can affect telomere length.

Download Full-text

Sex- and age‐dependent alterations of splenic immune cell profile and NK cell phenotypes and function in C57BL/6J mice

Immunity & Ageing ◽

10.1186/s12979-021-00214-3 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Kelly B. Menees ◽

Rachael H. Earls ◽

Jaegwon Chung ◽

Janna Jernigan ◽

Nikolay M. Filipov ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Sex Differences ◽

Nk Cells ◽

Immune Cell ◽

Nk Cell ◽

Spleen Weight ◽

Age Related ◽

And Function ◽

Cell Phenotypes

Abstract Background Physiological homeostasis decline, immunosenescence, and increased risk for multiple diseases, including neurodegeneration, are all hallmarks of ageing. Importantly, it is known that the ageing process is sex-biased. For example, there are sex differences in predisposition for multiple age-related diseases, including neurodegenerative and autoimmune diseases. However, sex differences in age-associated immune phenotypes are not clearly understood. Results Here, we examined the effects of age on immune cell phenotypes in both sexes of C57BL/6J mice with a particular focus on NK cells. We found female-specific spleen weight increases with age and concordant reduction in the number of splenocytes per gram of spleen weight compared to young females. To evaluate sex- and age-associated changes in splenic immune cell composition, we performed flow cytometry analysis. In male mice, we observed an age-associated reduction in the frequencies of monocytes and NK cells; female mice displayed a reduction in B cells, NK cells, and CD8 + T cells and increased frequency of monocytes and neutrophils with age. We then performed a whole blood stimulation assay and multiplex analyses of plasma cytokines and observed age- and sex-specific differences in immune cell reactivity and basal circulating cytokine concentrations. As we have previously illustrated a potential role of NK cells in Parkinson’s disease, an age-related neurodegenerative disease, we further analyzed age-associated changes in NK cell phenotypes and function. There were distinct differences between the sexes in age-associated changes in the expression of NK cell receptors, IFN-γ production, and impairment of α-synuclein endocytosis. Conclusions This study demonstrates sex- and age-specific alterations in splenic lymphocyte composition, circulating cytokine/chemokine profiles, and NK cell phenotype and effector functions. Our data provide evidence that age-related physiological perturbations differ between the sexes which may help elucidate sex differences in age-related diseases, including neurodegenerative diseases, particularly Parkinson’s disease, where immune dysfunction is implicated in their etiology.

Download Full-text

Supplementation with Selenium Restores Age-Related Decline in Immune Cell Function

Experimental Biology and Medicine ◽

10.3181/00379727-209-43909 ◽

1995 ◽

Vol 209 (4) ◽

pp. 369-375 ◽

Cited By ~ 35

Author(s):

M. Roy ◽

L. Kiremidjian-Schumacher ◽

H. I. Wishe ◽

M. W. Cohen ◽

G. Stotzky

Keyword(s):

Cell Function ◽

Immune Cell ◽

Immune Cell Function ◽

Age Related

Download Full-text

Use of Telomere Length as a Biomarker for Aging and Age-Related Disease

Current Translational Geriatrics and Experimental Gerontology Reports ◽

10.1007/s13670-012-0013-6 ◽

2012 ◽

Vol 1 (2) ◽

pp. 121-127 ◽

Cited By ~ 10

Author(s):

Michael Fossel

Keyword(s):

Telomere Length ◽

Related Disease ◽

Age Related

Download Full-text

The Intersection of Metformin and Inflammation

AJP Cell Physiology ◽

10.1152/ajpcell.00604.2020 ◽

2021 ◽

Author(s):

Leena P. Bharath ◽

Barbara S. Nikolajczyk

Keyword(s):

Mitochondrial Function ◽

Immune Cells ◽

Immune Cell ◽

Cell Types ◽

Remarkable Effect ◽

Tumor Onset ◽

Age Related ◽

Immune Mediated ◽

Autoimmune Conditions ◽

Near Term

The biguanide metformin is the most commonly used antidiabetic drug. Recent studies show that metformin not only improves chronic inflammation by improving metabolic parameters but also has a direct anti-inflammatory effect. In light of these findings, it is essential to identify the inflammatory pathways targeted by metformin to develop a comprehensive understanding of the mechanisms of action of this drug. Commonly accepted mechanisms of metformin action include AMPK activation and inhibition of mTOR pathways, which are evaluated in multiple diseases. Additionally, metformin's action on mitochondrial function and cellular homeostasis processes such as autophagy, is of particular interest because of the importance of these mechanisms in maintaining cellular health. Both dysregulated mitochondria and failure of the autophagy pathways, the latter of which impair clearance of dysfunctional, damaged, or excess organelles, affect cellular health drastically and can trigger the onset of metabolic and age-related diseases. Immune cells are the fundamental cell types that govern the health of an organism. Thus, dysregulation of autophagy or mitochondrial function in immune cells has a remarkable effect on susceptibility to infections, response to vaccination, tumor onset, and the development of inflammatory and autoimmune conditions. Here we summarize the latest research on metformin's regulation of immune cell mitochondrial function and autophagy as evidence that new clinical trials on metformin with primary outcomes related to the immune system should be considered to treat immune-mediated diseases over the near term.

Download Full-text