Social stress, epigenetics and immune function across bat lifespans

蝙蝠一生中的社会压力、表观遗传学和免疫功能

• 批准号: 10683249
• 负责人: GERALD S WILKINSON
• 金额: $ 30.16万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10683249
• 关键词: Address; Adult; Age; Aging; Animals; Bioinformatics; Biological Assay; Biological Markers; Body Size; Chiroptera; Complex; CpG Islands; Cross-Sectional Studies; DNA Methylation; DNA methylation profiling; Data; Data Analyses; Disease; Distant; Epigenetic Process; Exhibits; Family; Fathers; Female; Food; Gene Expression; Genetic; Genome; Goals; Health Status; Human; Immune; Immune response; Immunity; Immunologic Tests; Individual; Knowledge; Lactation; Leukocytes; Lipopolysaccharides; Location; Longevity; Longitudinal Studies; Mammals; Measures; Methods; Mononuclear; Mus; Natural Immunity; Natural experiment; Nose; Partner in relationship; Pathway interactions; Peripheral; Phase; Population; Predisposition; Reproductive Periods; Seasons; Sex Differences; Site; Social Behavior; Social Network; Social status; System; Tail; Testing; Variant; Virus; Women' s Group; age related; bisulfite sequencing; experience; father role; genomic biomarker; healthspan; immune function; male; member; reproductive; reproductive success; sex; social; social group; social integration; social situation; social stress; therapy development; whole genome

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.

概括 该项目的总体目标是确定由于差异导致的社会压力如何 社会地位或缺乏社会融合会影响蝙蝠一生的先天免疫力。 蝙蝠因其非凡的寿命和社交性而被提议进行研究。没有其他 哺乳动物群体的寿命与体型大小或社会性差异相当。在 此外，最近的证据表明，一些蝙蝠并没有表现出一些衰老和衰老的特征。 可以调节他们的免疫反应以耐受高水平的病毒暴露。四种 选择进行研究的物种具有远亲关系，包括来自三个物种的一些寿命最长的物种 不同的家庭，并且一直是涉及单独标记的长期研究的主题 动物，这使得它们非常适合衰老研究。目标1将使用基因 脂多糖离体刺激后单核白细胞的表达 (LPS) 量化一岁和年龄的免疫反应（即大于成人平均寿命） 男女个体以确定一生中免疫力是否存在性别差异。 DNA 甲基化将使用微阵列分析保守位点，然后使用 确定表观遗传衰老是否存在性别差异并识别基因组生物标志物 的老化。目标 2 将评估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。男性地位将由身体防御来决定 交配季节期间的雌性群体或来自父子关系的估计。目标 3 将评估 社会融合对两个群体基因表达和 DNA 甲基化年度变化的影响 其中之一将利用野生大矛鼻鱼雌性群体组成的变化 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交网络 使用圈养的吸血蝙蝠，吸血蝙蝠可能是蝙蝠中最复杂的社会系统。 该项目的 R61 阶段将解决更大的矛鼻蝙蝠的目标 1 和 2。 R33 该阶段将扩大目标 1 和 2 的范围，以包括另外三个物种，并将 解决目标 3。R33 相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 蝙蝠的生物标志物与人类的基因组生物标志物进行了比较。这种多物种方法 有潜力揭示有助于长寿的独特适应，而不仅仅是 反映了蝙蝠和其他哺乳动物之间的差异。

项目成果

Bats experience age-related hearing loss (presbycusis).

蝙蝠会出现与年龄相关的听力损失（老年性耳聋）。

• 发表时间: 2023-06
• 影响因子: 4.4
• 作者: Tarnovsky, Yifat Chaya;Taiber, Shahar;Nissan, Yomiran;Boonman, Arjan;Assaf, Yaniv;Wilkinson, Gerald S;Avraham, Karen B;Yovel, Yossi
• 通讯作者: Yovel, Yossi