Social stress, epigenetics and immune function across bat lifespans

总结 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，影响先天免疫在蝙蝠的寿命。 蝙蝠因其非凡的长寿和社会性而被提议进行研究。没有其他 哺乳动物群体表现出相当的寿命相对于身体大小或社会性的变化。在 此外，最近的证据表明，一些蝙蝠没有表现出几个老化的标志， 可以调节其免疫反应以耐受高水平的病毒暴露。四种 被选来研究的物种都是远亲，包括三个国家中一些寿命最长的物种。 不同的家庭，并一直是长期研究的主题，涉及个别标记 动物，这使得它们特别适合衰老研究。目标1将使用基因 脂多糖体外刺激后单核白色血细胞的表达 (LPS)量化1岁和1岁（即大于平均成人寿命）的免疫应答 两种性别的个体，以确定是否有免疫力在整个生命周期的性别差异。 DNA甲基化将使用微阵列分析保守位点，然后使用 以确定表观遗传衰老是否存在性别差异，并确定基因组生物标志物， 衰老的迹象目的2将评估这四个物种雄性的社会地位对这两个基因的影响 表达和DNA甲基化。男性的地位将取决于身体的防御能力， 雌性群体在交配季节或从估计父权。目标3将评估 社会融合对两个群体基因表达和DNA甲基化年度变化影响 方法，其中之一将利用野生大矛鼻雀雌性群体组成的变化， 蝙蝠和其他将利用社交网络测量在不同的空间和时间尺度 利用圈养的吸血蝙蝠，它们可能是所有蝙蝠中社会系统最复杂的。 该项目的R61阶段将解决更大的矛鼻蝙蝠的目标1和2。R33 第一阶段将扩大目标1和2的范围，包括另外三个物种，并将 目标3. R33阶段还将扩大DNA甲基化谱的范围， 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， 蝙蝠中的生物标志物与人类基因组中的生物标志物进行比较。这种多物种的方法 有可能揭示独特的适应性，有助于长寿， 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.