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老龄化与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来研究在自然条件下高度社会化背景下表观遗传对衰老的影响。这些研究可以产生与衰老过程普遍相关的新见解，并产生新的假设或概念，以刺激人类衰老研究。基于我们之前的人口统计学研究以及社会地位和行为对蜜蜂衰老的影响大于实际年龄的发现，我建议进一步研究蜜蜂工蜂的可塑性衰老模式，以解决早期生活压力因素、成体行为和社会干预如何决定个体生活史轨迹的问题。这些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，以阐明蜜蜂异常衰老可塑性的基因组特征。本研究的具体目的如下：1)确定早期发育和行为对衰老的影响：以成虫行为为协变量，研究发育过程中寄生虫应激对死亡率模式的影响。2)描述衰老可塑性社会调控的基因表达模式和表观遗传机制：在正常衰老或实验性衰老逆转的应激和非应激个体中，比较三个时间点特定组织的转录组和甲基组谱。所有实验都将在大量可识别个体的工人中进行，这些工人被安置在观察蜂箱中，以便进行人口统计分析。基于以往的研究、最新的方法进展以及对全面了解老龄化的日益增长的需求，这一建议是及时和创新的。它在一个独特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，阐明在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对学生研究的指导和培养下一代生物医学科学家的贡献。

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.