Age-related declines in immune response in a wild mammal are unrelated to immune cell telomere length.
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ABSTRACT:
SUBMITTER: Beirne C
PROVIDER: S-EPMC4810837 | biostudies-literature | 2016 Feb
REPOSITORIES: biostudies-literature
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Project description:Immunosenescence, the deterioration of immune system capability with age, may play a key role in mediating age-related declines in whole-organism performance, but the mechanisms that underpin immunosenescence are poorly understood. Biomedical research on humans and laboratory models has documented age and disease related declines in the telomere lengths of leukocytes ('immune cells'), stimulating interest their having a potentially general role in the emergence of immunosenescent phenotypes. However, it is unknown whether such observations generalise to the immune cell populations of wild vertebrates living under ecologically realistic conditions. Here we examine longitudinal changes in the mean telomere lengths of immune cells in wild European badgers (Meles meles). Our findings provide the first evidence of within-individual age-related declines in immune cell telomere lengths in a wild vertebrate. That the rate of age-related decline in telomere length appears to be steeper within individuals than at the overall population level raises the possibility that individuals with short immune cell telomeres and/or higher rates of immune cell telomere attrition may be selectively lost from this population. We also report evidence suggestive of associations between immune cell telomere length and bovine tuberculosis infection status, with individuals detected at the most advanced stage of infection tending to have shorter immune cell telomeres than disease positive individuals. While male European badgers are larger and show higher rates of annual mortality than females, we found no evidence of a sex difference in either mean telomere length or the average rate of within-individual telomere attrition with age. Our findings lend support to the view that age-related declines in the telomere lengths of immune cells may provide one potentially general mechanism underpinning age-related declines in immunocompetence in natural populations.
| S-EPMC4182606 | biostudies-literature
Project description:Telomere length (TL) shortens with age but telomere dynamics can relate to fitness components independent of age. Immune function often relates to such fitness components and can also interact with telomeres. Studying the link between TL and immune function may therefore help us understand telomere-fitness associations. We assessed the relationships between erythrocyte TL and four immune indices (haptoglobin, natural antibodies (NAbs), complement activity (CA) and heterophil-lymphocyte (HL) ratio; n = 477-589), from known-aged individuals of a wild passerine (Malurus coronatus). As expected, we find that TL significantly declined with age. To verify whether associations between TL and immune function were independent of parallel age-related changes (e.g. immunosenescence), we statistically controlled for sampling age and used within-subject centring of TL to separate relationships within or between individuals. We found that TL positively predicted CA at the between-individual level (individuals with longer average TL had higher CA), but no other immune indices. By contrast, age predicted the levels of NAbs and HL ratio, allowing inference that respective associations between TL and age with immune indices are independent. Any links existing between TL and fitness are therefore unlikely to be strongly mediated by innate immune function, while TL and immune indices appear independent expressions of individual heterogeneity.
| S-EPMC9043702 | biostudies-literature
Project description:BackgroundDyskeratosis congenita is a cancer-prone bone marrow failure syndrome caused by aberrations in telomere biology.Design and methodsWe studied 65 patients with dyskeratosis congenita and 127 unaffected relatives. Telomere length was measured by automated multicolor flow fluorescence in situ hybridization in peripheral blood leukocyte subsets. We age-adjusted telomere length using Z-scores (standard deviations from the mean for age).ResultsWe confirmed that telomere lengths below the first percentile for age are very sensitive and specific for the diagnosis of dyskeratosis congenita. We provide evidence that lymphocytes alone and not granulocytes may suffice for clinical screening, while lymphocyte subsets may be required for challenging cases, including identification of silent carriers. We show for the first time using flow fluorescence in situ hybridization that the shortest telomeres are associated with severe variants (Hoyeraal-Hreidarsson and Revesz syndromes), mutations in DKC1, TINF2, or unknown genes, and moderate or severe aplastic anemia. In the first longitudinal follow up of dyskeratosis congenita patients, we demonstrate that telomere lengths decline with age, in contrast to the apparent stable telomere length observed in cross-sectional data.ConclusionsTelomere length by flow fluorescence in situ hybridization is an important diagnostic test for dyskeratosis congenita; age-adjusted values provide a quantitative measure of disease severity (clinical subset, mutated gene, and degree of bone marrow failure). Patients with dyskeratosis congenita have accelerated telomere shortening. This study is registered at www.clinicaltrials.gov (identifier: NCT00027274).
| S-EPMC3291588 | biostudies-literature
Project description: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.
| S-EPMC7423055 | biostudies-literature
Project description:BackgroundTelomere length provides a physiological proxy for accumulated stress in animals. While there is a growing consensus over how telomere dynamics and their patterns are linked to life history variation and individual experience, knowledge on the impact of exposure to different stressors at a large spatial scale on telomere length is still lacking. How exposure to different stressors at a regional scale interacts with individual differences in life history is also poorly understood. To better understand large-scale regional influences, we investigated telomere length variation in moose (Alces alces) distributed across three ecoregions. We analyzed 153 samples of 106 moose representing moose of both sexes and range of ages to measure relative telomere lengths (RTL) in white blood cells.ResultsWe found that average RTL was significantly shorter in a northern (montane) and southern (sarmatic) ecoregion where moose experience chronic stress related to severe summer and winter temperatures as well as high anthropogenic land-use compared to the boreal region. Our study suggests that animals in the northern boreal forests, with relatively homogenous land use, are less disturbed by environmental and anthropogenic stressors. In contrast, animals in areas experiencing a higher rate of anthropogenic and environmental change experience increased stress.ConclusionAlthough animals can often adapt to predictable stressors, our data suggest that some environmental conditions, even though predictable and ubiquitous, can generate population level differences of long-term stress. By measuring RTL in moose for the first time, we provide valuable insights towards our current understanding of telomere biology in free-ranging wildlife in human-modified ecosystems.
| S-EPMC9426267 | biostudies-literature
Project description:Age-related changes in immunity are well documented in humans and laboratory mammals. Using blood samples collected from wild Soay sheep, we show that pronounced differences in T-cell subsets and inflammatory markers amongst age classes are also evident under natural conditions. These shifts parallel those observed in mammals experiencing protected environments. We found progressive declines in the proportion of naïve CD4 T cells with age, a precipitous drop in ?? T cells after the second year of life and an increase in acute phase protein levels amongst geriatric sheep. Our findings suggest immune aging patterns observed in laboratory and domestic mammals may generalize to more complex, challenging environments and could have fitness costs under natural conditions.
| S-EPMC3397677 | biostudies-literature
Project description:The ability to estimate age and determine the growth status of free-ranging dugongs (Dugong dugon) is vital to providing insight into the basic biology of this endangered species. Currently, age estimation in dugong carcasses relies on counting dentin growth layer groups (GLGs) in tusks, but a disadvantage is they need to be intact. We explored whether measures of telomere length could be used as an alternative approach to age estimation in dugongs given that in other species, telomere length and age are inversely related. In this study, relative telomere length (rTL) was measured by qPCR in skin samples from 24 dugongs of varying ages determined by counts of GLGs. In addition, relationships between age by GLG counts and body weight and length and were examined. Our findings indicate that age estimated by GLGs was negatively correlated with telomere length using the logistic formula with a rate of telomere attrition of approximately 0.036 rTL/year between the ages of 5-20 years. By comparison, both body weight and length were positively correlated with GLG-based age, with growth rates of ~8.8 kg/year for weight and ~3.58 cm/year for length, respectively. After that, growth rates slowed substantially and then plateaued. The results suggest that physical maturity in dugongs occurs at 20 years of age and that measures of rTL might serve as a tool for age estimation in dugongs, living and deceased.
| S-EPMC7666544 | biostudies-literature
Project description:Mounting evidence suggests that average telomere length reflects previous stress and predicts subsequent survival across vertebrate species. In humans, leucocyte telomere length (LTL) is consistently shorter during adulthood in males than in females, although the causes of this sex difference and its generality to other mammals remain unknown. Here, we measured LTL in a cross-sectional sample of free-living Soay sheep and found shorter telomeres in males than in females in later adulthood (>3 years of age), but not in early life. This observation was not related to sex differences in growth or parasite burden, but we did find evidence for reduced LTL associated with increased horn growth in early life in males. Variation in LTL was independent of variation in the proportions of different leucocyte cell types, which are known to differ in telomere length. Our results provide the first evidence of sex differences in LTL from a wild mammal, but longitudinal studies are now required to determine whether telomere attrition rates or selective disappearance are responsible for these observed differences.
| S-EPMC5484296 | biostudies-literature
Project description:PurposeRelative telomere length (RTL) is a biomarker for physiological aging. Premature shortening of telomeres is associated with oxidative stress, which is one possible pathway that might contribute to age-related macular degeneration (AMD). We therefore aimed to investigate the association between RTL and AMD in a well-characterized group of elderly individuals.MethodsWe measured RTL in participants of the AugUR study using a multiplex quantitative PCR-based assay determining the ratio between the telomere product and a single-copy gene product (T/S ratio). AMD was assessed by manual grading of color fundus images using the Three Continent AMD Consortium Severity Scale.ResultsAmong the 2262 individuals 70 to 95 years old (627 with AMD and 1635 without AMD), RTL was significantly shorter in individuals with AMD compared to AMD-free participants. In age- and sex-adjusted logistic regression analyses, we observed an 8% higher odds for AMD per 0.1 unit shorter RTL (odds ratio [OR] = 1.08; 95% confidence interval [CI], 1.02-1.14; P = 0.005). The estimates remained stable when adjusted for smoking, high-density lipoprotein cholesterol, cardiovascular disease, diabetes, and hypertension. Interestingly, this association was only present in women (OR = 1.14; 95% CI, 1.06-1.23; P < 0.001), but not in men (OR = 1.01; 95% CI, 0.93-1.10; P = 0.76). A significant sex-by-RTL interaction on AMD was detected (P = 0.043).ConclusionsOur results show an association of RTL with AMD that was restricted to women. This is in line with altered reactive oxygen species levels and higher telomerase activity in women and provides an indication for a sex-differential pathway for oxidative stress and AMD.
| S-EPMC9150829 | biostudies-literature
Project description:Ageing is characterized by the impairment of the acute innate immune response and the upregulation of low-grade inflammation, i.e. inflammaging. At the cellular level, telomeres are considered as a marker of biological ageing as their length is progressively eroded in the absence of repair mechanisms. However, the link between telomeres and inflammaging remains underexplored. We aimed to identify proteins that are differentially expressed between age classes in response to an acute inflammatory challenge. We challenged young (two months) and old (12 months) C57BL/6 mice using bacterial lipopolysaccharide (LPS) and measured telomere length and proteomic profiles in splenocytes. In total, 233 out of the 1966 proteins we quantified differed among experimental groups. A hierarchical clustering analysis revealed that nine of those 233 proteins were differently expressed among the experimental groups. Young mice responded to LPS by increasing the expression of proteins involved in the innate immune response, and interestingly, in telomere length maintenance. However, this regulation was impaired at older ages. These results are in agreement with the assumption that the strength of selection declines with age, potentially explaining the maintenance of costly, dysregulated, immune responses at old age. We suggest that the immune response is competing with the telomere maintenance process, highlighting how telomeres reflect the ageing trade-off even in a species where telomere length is not related to lifespan.
| S-EPMC6283940 | biostudies-literature