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

博士论文研究：灵长类动物的衰老表型和衰老相关的分泌表型

• 批准号: 2041654
• 负责人: James Higham
• 金额: $ 2.43万
• 依托单位: New York University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2041654&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Research; Aging; phenotypes

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.

衰老与生物、生理和功能变化有关，这些变化反映了整个生命周期中能量分配的进化权衡。该项目使用非人灵长类动物模型来检查与年龄相关的基因表达变化，并研究这些变化与年龄相关的表型下降之间的关系。这个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改变来帮助开发新的延长寿命的疗法，而不仅仅是在老年。该项目支持一名女研究生接受实验室、生物信息学和统计培训。她还担任教育工作者，通过她继续参与高中课程，为来自服务水平低下社区的学生提供指导和研究机会。生活史理论认为，生命早期的生长和繁殖以及生命后期的躯体维护之间的进化权衡是生活史事件发生的时间。然而，这些进化的权衡背后的分子机制尚未完全理解。细胞衰老和由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权衡。该项目检验了SASP因子表达随年龄变化并与非人灵长类动物衰老表型相关的假设。研究者将生成横截面、组织特异性转录组学数据，这些数据将用于表征SASP表达随年龄、性别和组织类型的变化。研究人员将计算与年龄相关的表型下降的措施，以评估SASP表达的变化是否与衰老表型有关。该奖项反映了NSF的法定使命，并已被认为是值得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的支持。

项目成果

Conserved and distinct signatures of transcriptional aging across tissues in rhesus macaques

恒河猴跨组织转录衰老的保守且独特的特征

• DOI: 10.1002/ajpa.24731
• 发表时间: 2023
• 期刊: American Journal of Biological Anthropology
• 作者: Newman, L. E.

The biology of aging in a social world: Insights from free-ranging rhesus macaques

• DOI: 10.1016/j.neubiorev.2023.105424
• 发表时间: 2023-10-23
• 期刊: NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
• 影响因子: 8.2
• 作者: Newman，Laura E.;Testard，Camille;Highama，James P.
• 通讯作者: Highama，James P.