Social stress, epigenetics and immune function across bat lifespans

摘要 这个项目的首要目标是确定社会压力，无论是由于差异 在社会地位或缺乏社会融合的情况下，会影响蝙蝠的先天免疫力。 蝙蝠之所以被提出进行研究，是因为它们非凡的寿命和社会性。没有其他人了 哺乳动物群体表现出与身体大小或社会性变化相类似的长寿。在……里面 此外，最近的证据表明，一些蝙蝠没有表现出几个衰老和 可以调节它们的免疫反应，以耐受高水平的病毒暴露。这四个物种 被选中进行研究的是远亲，包括三个物种中一些最长寿的物种 不同的家庭，并一直是涉及单独标记的长期研究的对象 动物，这使得它们特别适合于衰老研究。AIM 1将使用基因 脂多糖体外刺激单核白细胞的表达 (LP)量化一岁和一岁(即大于平均成年寿命)的免疫反应 以确定在寿命内是否存在性别差异的免疫力。 DNA甲基化将使用微阵列进行分析，分析保守的位点，然后使用 确定表观遗传衰老是否存在性别差异并鉴定基因组生物标记物 衰老的问题。目标2将评估这四个物种的男性的社会地位对这两个基因的影响 表达和DNA甲基化。男性身份将通过以下两种方式确定： 雌性群体在交配季节或从亲子关系的估计。目标3将评估 社会融合对两个群体基因表达和DNA甲基化年际变化的影响 其中一种方法是利用野生大枪鱼雌性群体组成的差异 蝙蝠和其他蝙蝠将利用在不同空间和时间尺度上测量的社会网络 使用圈养的吸血蝙蝠，它们的社会制度可能是所有蝙蝠中最复杂的。 该项目的R61阶段将解决更大的长吻蝙蝠的目标1和目标2。R33 阶段将扩大目标1和目标2的范围，以包括另外三个物种，并将 解决目标3.R33阶段还将通过以下方式扩大DNA甲基化分析的范围 使用全基因组亚硫酸氢盐测序来确定性别特异性衰老的程度 蝙蝠体内的生物标记物与人类基因组中的生物标记物进行了比较。这种多物种的方法 有可能揭示出有助于长寿的独特适应能力，而不仅仅是 反映了蝙蝠和其他哺乳动物之间的差异。

Summary The overarching goal of this project is to determine how social stress, due either to differences in social status or lack of social integration, influences innate immunity over the lifespan of bats. Bats are proposed for study because of their extraordinary longevity and sociality. No other mammalian group exhibits comparable longevity relative to body size or variation in sociality. In addition, recent evidence indicates that some bats do not exhibit several hallmarks of aging and can modulate their immune response to tolerate high levels of virus exposure. The four species chosen for study are distantly related, include some of the longest-lived species from three different families, and have been the subject of long-term studies involving individually marked animals, which makes them uniquely suitable for an aging study. Aim 1 will use gene expression of mononuclear white blood cells after ex vivo stimulation with lipopolysaccharide (LPS) to quantify immune response in first year and old (i.e. greater than mean adult lifespan) individuals of both sexes to determine if there are sex differences in immunity over the lifespan. DNA methylation will be profiled using a microarray that assays conserved sites and then used to determine if there are sex differences in epigenetic aging and to identify genomic biomarkers of aging. Aim 2 will evaluate the effect of social status in males of the four species on both gene expression and DNA methylation. Male status will be determined either from physical defense of female groups during the mating season or from estimates of paternity. Aim 3 will assess the effect of social integration on annual change in gene expression and DNA methylation in two ways, one of which will utilize variation in female group composition in wild greater spear-nosed bats and the other will utilize social networks measured at different spatial and temporal scales using captive vampire bats, which have perhaps the most complex social system of any bat. The R61 phase of the project will address Aims 1 and 2 in greater spear-nosed bats. The R33 phase will expand the scope of Aims 1 and 2 to include three additional species and will address Aim 3. The R33 phase will also expand the scope of the DNA methylation profiling by using whole genome bisulfite sequencing to determine the extent to which sex-specific aging biomarkers in bats compare to those in humans across the genome. This multispecies approach has the potential to reveal unique adaptations that contribute to longevity and do not simply reflect differences between a bat and other mammals.