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

描述（由申请人提供）：我的长期目标是在基因组，有机体和生物人口学水平上了解衰老和社会进化之间的关系。我使用比较蜜蜂模型，提供了许多实验机会，研究在自然条件下，在高度社会化的背景下，表观遗传对衰老的影响。这些研究可以产生对衰老过程具有普遍意义的新见解，并产生新的假设或概念，以刺激人类衰老研究。基于我们以前的人口统计学研究和发现，蜜蜂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人的塑料老化模式，以解决早期生活压力，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的转录组和甲基化组的调查中进一步研究，以阐明蜜蜂异常衰老可塑性的基因组特征。该提案有以下具体目标：1）鉴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率模式的影响。2)描述基因表达模式和表观遗传机制，这些机制是衰老可塑性的社会调节的基础：将在经历正常衰老或实验性衰老逆转的应激和非应激个体之间的三个时间点比较特定组织中的转录组和甲基化谱。所有实验都将在大量可识别个体的工蚁中进行，这些工蚁被安置在观察蜂箱中，以便进行人口统计学分析。受以前的研究，最近的方法进步和日益增长的需要，全面了解老龄化的动机，这一建议是及时和创新的。它解决了基本的老年学问题，在一个合适的模型系统。它将提供新的见解，阐明实验生物系统中衰老的社会维度，为未来的研究产生新的假设。这笔资金将使我能够扩大我对指导学生研究和培养下一代生物医学科学家的奉献。

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.