Biodemography and Genomics of Aging Trajectories and Plasticity in a Social Model

描述(由申请者提供)：我的长期目标是在基因组、组织和生物统计学水平上理解衰老和社会进化之间的关系。我使用比较蜜蜂模型，它提供了许多实验机会，在自然条件下，在高度社会化的背景下研究表观遗传对衰老的影响。这些研究可以对衰老过程产生普遍相关的新见解，并产生新的假设或概念来刺激人类衰老研究。基于我们之前的人口统计学研究和发现，蜜蜂的衰老更多地受到社会地位和行为的影响，而不是年龄，我建议进一步研究蜜蜂工作者的塑料老化模式，以解决早期生活应激源、成年行为和社会干预如何决定个人生活史轨迹的问题。预测的影响将在蜜蜂转录组和甲基组的调查中进一步研究，以阐明蜜蜂异常老化可塑性的基因组特征。该建议有以下具体目标：1)确定早期发育和行为对衰老的影响：将以成人行为为协变量研究发育期间寄生虫应激对死亡模式的影响。2)衰老可塑性社会调控的基因表达模式和表观遗传学机制的描述：在经历正常衰老或实验性衰老逆转的应激和非应激个体中，将在三个时间点比较特定组织中的转录组和甲基组的谱。所有实验都将在大量可识别身份的工蚁中进行，这些工蚁被安置在观察室中，以便进行人口统计学分析。在以前的研究、最近的方法学进步和对全面了解老龄化的日益增长的需求的推动下，这项建议是及时的和创新的。它在一个特别适合的模型系统中解决了基本的老年学问题。它将提供新的见解，阐明实验生物学系统中衰老的社会层面，为未来的研究产生新的假设。这笔资金将使我能够更多地致力于指导学生研究和培养下一代生物医学科学家。

DESCRIPTION (provided by applicant): My long-term goal is to understand the relation between aging and social evolution at the genomic, organismal, and biodemographic level. I use the comparative honey bee model that offers many experimental opportunities to study epigenetic influences on aging in a highly social context under natural conditions. These studies can yield new insights of general relevance into aging processes and generate novel hypotheses or concepts to stimulate human aging studies. Based on our previous demographic studies and findings that honey bees senescence is more influenced by social status and behavior than by chronological age, I propose to study the plastic aging patterns in honey bee workers further to address the questions how early life stressors, adult behavior, and social interventions determine individual life history trajectories. The predicted influences will be furter studied in surveys of the bees' transcriptome and methylome to elucidate genomic signatures of the exceptional aging plasticity of honey bees. The proposal has the following specific aims: 1) Identification of early developmental and behavioral influences on aging: The effect of parasite stress during development on mortality patterns will be studied with adult behavior as covariate. 2) Description of gene expression patterns and epigenetic mechanisms that underlie the social regulation of aging plasticity: Transcriptome and methylome profiles in specific tissues will be compared at three time points between stressed and unstressed individuals that experience normal aging or experimental aging reversal. All experiments will be conducted in large cohorts of individually identifiable workers housed in observation hives to enable demographic analyses. Motivated by previous studies, recent methodological advances and the growing need for a comprehensive understanding of aging, this proposal is timely and innovative. It addresses fundamental gerontological questions in a uniquely-suited model system. It will provide novel insights that illuminate the social dimension of aging in an experimental biological system to generate new hypotheses for future research. The funding would allow me to expand my dedication to mentoring student research and fostering the next generation of biomedical scientists.