Data from: Age-related declines in immune response in a wild mammal are unrelated to immune cell telomere length

Senescence has been hypothesised 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 IFNy 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.

部分假说认为衰老的产生部分源于免疫功能随年龄增长的衰退，但自然种群中个体内免疫功能随年龄变化的模式与驱动因素，至今几乎仍未被探索。本研究基于对野生欧洲獾（*Meles meles*）的长期流行病学调查，（1）提供了关键免疫信号细胞因子干扰素-γ（Interferon-gamma, IFNγ）在离体淋巴细胞刺激下的应答水平在个体内随年龄增长出现衰退的证据；（2）探究了该衰退速率个体差异的三类推定驱动因素：性别、疾病状态与免疫细胞端粒长度（immune-cell telomere length, ICTL）。个体内免疫应答随年龄衰退的速率显著高于种群水平的衰退速率，这表明IFNγ应答较弱的个体在该种群中被选择性淘汰。IFNγ应答水平似乎会随牛结核病感染的进展而降低（与年龄无关），且雄性个体的应答水平弱于雌性。不过，性别与疾病状态均未对IFNγ应答随年龄衰退的速率产生影响。类似地，尽管免疫细胞端粒长度也会随年龄增长而缩短，但免疫细胞端粒长度的变异既无法预测种群间也无法预测个体内IFNγ应答水平的变异。本研究的结果为野生哺乳动物中存在个体内免疫功能随年龄衰退的现象提供了证据，并揭示了该现象背后潜在的复杂作用机制。