BII: IISAGE - Discovering the mechanisms and evolution of aging differences between females and males

在许多动物中，雌性或雄性衰老更快或寿命更长。这种老龄化差异对生物多样性、保护、农业和人类健康具有重大影响。例如，在人类中，女性比男性活得更长，而且女性和男性在身体衰退和疾病方面表现出的衰老方式不同。是什么导致了自然界中出现的不同的衰老差异模式尚不清楚。IISAGE生物综合研究所将确定多种生物过程如何导致女性和男性之间的衰老差异，并揭示它们的进化史。IISAGE将汇集生物学领域的专业知识，以确定支配女性和男性衰老差异的分子机制和普遍规律。紧密结合的项目将测试侧重于女性和男性在基因组结构、生物生物学和表型可塑性方面的差异的假设，以了解衰老方面的差异。IISAGE将定义分子、组织和种群水平上的过程如何相互作用，以产生雌性和雄性之间的衰老差异。与其科学使命相结合，IISAGE的培训、教育和推广计划将增加STEM的多样性，并为学员在不同的职业和多学科团队中工作做好准备。IISAGE暑期项目将招收来自STEM代表性不足群体的50名本科生。一项公民科学项目将邀请宠物主人和K-12年级的学生为IISAGE的科学目标收集数据。确定解释衰老差异的规则具有挑战性，因为女性和男性之间存在许多差异。IISAGE将确定基因组结构、生物生物学和表型可塑性如何导致衰老的差异，并定义在进化上保守的和特定于分类单元的机制，控制雌性和雄性之间的这些衰老差异。为此，IISAGE将生产新的分析工具和数百个匹配的数据集，分析数十个物种的基因表达和染色质。通过跨学科、方法和生物组织水平的整合，IISAGE将为基因组结构、生物生物学和表型可塑性如何相互作用并导致衰老差异开发预测模型。IISAGE的方法将包括来自野生物种、实验室操作和公民科学家的数据，以提供对控制女性和男性衰老差异的机制的前所未有的见解。从IISAGE的工作中获得的数据集、工具和见解将引起从基础生物学家到医学和保护领域的翻译研究人员的科学家的兴趣，而IISAGE的推广和培训活动将吸引公众。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

In many animals, either females or males age faster or have a longer lifespan. This aging difference has significant implications for biodiversity, conservation, agriculture, and human health. In humans, for example, females live longer than males, and females and males differ in how aging manifests itself in terms of physical decline and disease. What causes the diverse patterns of aging differences seen in nature is unknown. The IISAGE Biology Integration Institute will determine how multiple biological processes contribute to differences in aging between females and males and uncover their evolutionary history. IISAGE will bring together expertise from across biology to identify the molecular mechanisms and generalizable rules that govern differences in aging between females and males. Tightly integrated projects will test hypotheses focused on differences between females and males in genome architecture, organismal biology, and phenotypic plasticity to understand differences in aging. IISAGE will define how processes at the molecular, organismal, and population level interact to generate aging differences between females and males. Integrated with its scientific mission, IISAGE’s training, education, and outreach program will increase diversity in STEM and prepare trainees to work in diverse careers and in multidisciplinary teams. The IISAGE summer program will engage 50 undergraduates from groups underrepresented in STEM. A citizen science project will engage pet owners and K-12 students to collect data for IISAGE scientific goals.Identifying rules that explain differences in aging is challenging because there are many differences between females and males. IISAGE will determine how genome architecture, organismal biology, and phenotypic plasticity generate differences in aging and define evolutionarily conserved and taxon-specific mechanisms controlling those differences in aging between females and males. To do so, IISAGE will produce novel analysis tools and hundreds of matched datasets profiling gene expression and chromatin in dozens of species. By integrating across disciplines, approaches, and levels of biological organization, IISAGE will develop predictive models for how genome architecture, organismal biology, and phenotypic plasticity can interact and lead to differences in aging. IISAGE’s approach will include data from wild species, laboratory manipulations, and citizen scientists to provide unprecedented insights into the mechanisms controlling differences in aging between females and males. The datasets, tools, and insights derived from IISAGE’s work will be of interest to scientists ranging from basic biologists to translational researchers in the medical and conservation fields, while IISAGE outreach and training activities will engage the public.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.