Abstract
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 (IFNγ), 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 IFNγ responses are selectively lost from this population. IFNγ 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 IFNγ response. Similarly, while ICTL also declines with age, variation in ICTL predicted neither among- nor within-individual variation in IFNγ 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.
Highlights
Late-life declines in survival and reproductive success are pervasive in wild populations [1], but the physiological changes that give rise to such declines remain poorly understood
As we have previously shown that within-individual age-related declines in immune cell (leucocyte) telomere length (ICTL) occur in this population [25], and on the basis of the putative mechanisms outlined above for causal links between ICTL and the strength of the pro-inflammatory cytokine response, we investigate whether these two immune traits are positively associated by testing the following two predictions: (iii) that individuals that show greater proinflammatory cytokine responses show longer average ICTLs; and (iv) that within-individual variation in the pro-inflammatory cytokine response is positively correlated with within-individual variation in ICTL
In order to determine if (i) individuals that show stronger average IFNg responses show longer average ICTLs and/or (ii) within-individual variation in the IFNg response is positively correlated with within-individual variation in ICTL we used a Bayesian mixed-model approach, in R [49]. The advantage of this approach is that it allows examination of the posterior correlation between the magnitudes of the IFNg response and ICTL, while controlling for effects of both fixed and random factors on both immune traits, which could influence the apparent relationship between the traits
Summary
Late-life declines in survival and reproductive success are pervasive in wild populations [1], but the physiological changes that give rise to such declines remain poorly understood. In order to determine if (i) individuals that show stronger average IFNg responses show longer average ICTLs ( positive among-individual covariance between these two variables) and/or (ii) within-individual variation in the IFNg response (for example, as individuals age) is positively correlated with within-individual variation in ICTL ( positive within-individual covariance) we used a Bayesian mixed-model approach ( package MCMCglmm, Markov chain Monte Carlo generalized linear mixed models; [48]), in R [49] The advantage of this approach is that it allows examination of the posterior correlation (and its corresponding confidence interval) between the magnitudes of the IFNg response and ICTL, while controlling for effects of both fixed (e.g. bTB status and sex) and random factors (e.g. assay plate) on both immune traits, which could influence the apparent relationship between the traits. We repeated the modelling process with the fixed effects of age included for both traits (partitioned age; mean age and D age), but as the inclusion of partitioned age did not alter the findings of the covariance analysis we do not discuss this secondary analysis further
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