Senescence in wild European badgers: the roles of parental age effects and immunosenescence

人们普遍认识到，人类经历了与年龄相关的免疫功能下降，导致老年时对传染病的易感性增加。虽然最近的研究也揭示了野生动物种群的免疫系统老化，但其对野生动物疾病动态的影响很少得到调查。这一点很重要，因为疾病易感性的个体差异（预期会因年龄增长而产生）会显著影响流行病学模型对疾病动态和控制措施有效性的预测。因此，该项目将利用对其主要野生动物宿主（欧洲獾的牛结核病[bTB]）的一种具有重要经济意义的疾病进行为期40年的特殊实地研究，以调查衰老对疾病动态的影响以及调解这种联系的机制。我们的CASE合作伙伴将提供无与伦比的流行病学和生活史数据集，这些数据集来自于对加利福尼亚州伍德彻斯特公园的欧洲獾进行的长期（1976年至今）捕获标记再捕获（CMR）研究。每季度对20-25个社会群体进行捕获，再加上bTB诊断测试以及免疫和形态学评估，已经获得了5000只已知年龄的獾的终身记录。迄今为止，我们的衰老研究（由Young领导）揭示了与年龄相关的身体状况和两个关键免疫特征（ICTL和IFNy反应）的下降，这两个特征的水平下降与bTB感染有关。我们现在提出一项新颖而及时的调查，研究这些与年龄有关的衰退的流行病学后果。该项目将包括三个工作包：年龄相关的疾病抵抗和恢复能力下降：测试和机制首先，我们将建立现有的獾bTB状态依赖CMR模型，以测试老年流行病学转变（bTB感染，进展和疾病引起的死亡率）概率的增加。其次，我们将通过测试这些转变是否也由年龄敏感免疫特征（ICTL和IFNy反应）和身体状况预测来研究候选机制。2. 父母年龄对后代抗病性和恢复力的影响生物医学研究表明，衰老还可能通过对后代疾病易感性的跨代影响产生重要的流行病学影响。因此，我们将首次在自然人群中调查父亲和母亲的受孕年龄（可能通过不同的机制起作用）对后代这些流行病学转变的概率的影响。我们将在Aim 1中开发的状态依赖CMR模型中拟合母亲和父亲的年龄（来自最近的遗传亲子关系分配）以及个人自己的年龄。我们还将通过测试母亲和父亲的年龄对后代ICTL、IFNy反应和身体状况的影响来研究候选机制。3. 结核杆菌感染会加剧衰老吗？考虑到慢性感染有可能加重躯体损伤并减少修复，衰老过程本身可能反过来被bTB感染加速。尽管目前人们对衰老轨迹变化的原因非常感兴趣，但对疾病的影响仍然知之甚少。因此，我们将调查bTB感染对生存率、生殖成功率和ICTL的性别特异性年龄相关下降的发生率和比率的影响

It is widely recognised that humans experience age-related declines in immune function, leading to increased susceptibility to infectious disease in old age. While recent research has also revealed immune-system ageing in wild animal populations, its effects on the dynamics of wildlife disease have rarely been investigated. This is significant, as individual variation in disease susceptibility (as would be expected to arise from ageing) can markedly impact the predictions of epidemiological models about disease dynamics and the effectiveness of control measures. This project will therefore utilise an exceptional 40 year field study of an economically-significant disease in its primary wildlife host (bovine tuberculosis [bTB] in the European badger) to investigate the impacts of ageing on disease dynamics and the mechanisms that mediate such links. Our CASE partners will provide an unparalleled epidemiological and life-history data set arising from a long-running (1976 - present) capture mark recapture (CMR) study of European badgers at Woodchester Park, Glos. Quarterly trapping at 20-25 social groups, coupled with diagnostic bTB tests and immunological and morphological assessments, have yielded life-long records for >3000 known-age badgers. Our ageing research to date (led by Young) has revealed age-related declines in body condition and two key immune traits (ICTL and the IFNy response), and that reduced levels of each are linked with bTB infection. We now propose a novel and timely investigation of the epidemiological consequences of these age-related declines. The project will comprise three work packages: 1. Age-related declines in disease resistance and resilience: test and mechanismsFirst, we will build on our existing state-dependent CMR models of bTB in badgers to test for late-life increases in the probability of epidemiological transitions (bTB infection, progression and disease-induced mortality)]. Second, we will investigate candidate mechanisms by testing whether these transitions are also predicted by age-sensitive immune traits (ICTL and the IFNy response) and body condition. 2. Parental age effects on offspring disease resistance and resilienceBiomedical studies suggest that ageing could also have important epidemiological consequences via transgenerational effects on disease susceptibility in offspring. We will therefore investigate, for the first time in a natural population, the impacts of paternal and maternal age at conception (which may act through distinct mechanisms) on the probability of these epidemiological transitions in offspring. We will fit maternal and paternal age (derived from recent genetic parentage assignments) alongside an individual's own age in the state-dependent CMR models developed in Aim 1. We will also investigate candidate mechanisms by testing for maternal and paternal age effects on offspring ICTL, IFNy response and body condition. 3. Does bTB infection exacerbate ageing?The ageing process itself could in turn be accelerated by bTB infection, given the potential for chronic infections to elevate somatic damage and reduce repair. Despite intense current interest in the causes of variation in ageing trajectories, the impact of disease remains poorly understood. We will therefore investigate the impact of bTB infection on the onset and rates of sex-specific age-related declines in survival, reproductive success and ICTL