Doctoral Dissertation Research: Aging phenotypes and the senescence associated secretory phenotype in primates

衰老与生物、生理和功能变化有关，这些变化反映了生命周期中能量分配的进化权衡。该项目使用非人类灵长类动物模型来检查年龄相关基因表达的变化，并调查这些变化与年龄相关表型下降之间的关系。这一博士论文项目推进了关于灵长类动物衰老和生活史的知识，并有可能通过识别在整个生命周期中发生的器官特异性基因表达的变化，而不仅仅是在老年时，来帮助开发新的延长生命的疗法。该项目支持一名女研究生参加实验室、生物信息学和统计学培训。她还通过继续参与高中项目担任教育工作者，这些项目为来自缺乏服务的社区的学生提供指导和研究机会。生活史理论假设，早期生命发育和生殖以及后期躯体维持之间的权衡进化是生活史事件发生的时间安排的原因。然而，这些进化权衡背后的分子机制并不完全清楚。细胞衰老和衰老细胞分泌的蛋白质(衰老相关分泌表型，SASP)被预测负责在分子水平上调节这些生活史的权衡。该项目测试了SASP因子表达随年龄变化的假设，并与非人灵长类动物的衰老表型有关。研究人员将产生横截面的、特定于组织的转录数据，这些数据将被用来描述SASP表达随年龄、性别和组织类型的变化。然后，研究人员将计算与年龄相关的表型下降的衡量标准，以评估SASP表达的变化是否与衰老表型有关。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Aging is associated with biological, physiological, and functional changes that reflect evolutionary trade-offs in energy allocation across the lifespan. This project uses a non-human primate model to examine age-associated gene expression changes and to investigate the relationship between these changes and age-related phenotypic decline. This doctoral dissertation project advances knowledge about senescence and life history in primates and has the potential to aid in the development of novel life-extending therapies by identifying alterations in organ-specific gene expression that occur across the lifespan, not just in old age. The project supports a female graduate student in laboratory, bioinformatic, and statistical training. She also serves as an educator through her continued involvement in high school programs that provide students from underserved communities with mentoring and research opportunities.Life history theory posits that evolved trade-offs between early-life growth and reproduction and later-life somatic maintenance are responsible for the timing of life history events. However, the molecular mechanisms underlying these evolved trade-offs are not fully understood. Cellular senescence and the proteins secreted by senescent cells (the senescence associated secretory phenotype, SASP) are predicted to be responsible for modulating these life history trade-offs on a molecular level. This project tests the hypothesis that SASP factor expression changes with age and is associated with aging phenotypes in non-human primates. The investigator will generate cross-sectional, tissue-specific transcriptomic data that will be used to characterize changes in SASP expression with age, sex, and tissue type. The researchers will then calculate measures of age-related phenotypic decline to evaluate whether changes in SASP expression are associated with aging phenotypes.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.