Epigenetic processes and biological senescence in humans

生物衰老的速度因个体而异，受到遗传和环境因素的影响。这种变化对人类学研究和法医实践提出了挑战，即根据衰老和虚弱的骨骼测量来确定一个人死亡时的年龄。该项目利用来自活体和死后临床队列的表观遗传和成像数据来研究基因甲基化与骨骼脆弱之间的关系，并提出了理解过去和现在人类衰老模式的方法。这项研究的结果在波士顿科学博物馆、新墨西哥州阿尔伯克基的麦克斯韦博物馆和哈佛大学的沃伦解剖博物馆与公众分享。该项目支持从小学到研究生阶段的学生科学教育和培训机会（医学生和研究生）。波士顿科学博物馆计划通过为对STEM感兴趣的女孩举办的活动和麦克斯韦博物馆的教育项目，向STEM领域代表性不足或服务不足的群体进行宣传。该项目采用先进的成像方法和表观遗传学分析，采用新颖的跨学科方法进一步表征年龄、性别和骨骼质量/数量之间的关系，特别是在死后获得的骨骼中。研究人员：（1）提供方法学概念验证，证明在来自骨骼遗骸的股骨和牙齿样品中类似地观察到源自骨质疏松症活体患者的股骨和血液样品的DNA中基因的表观遗传修饰，（2）鉴定上述基因在男性和女性中的表观遗传修饰的任何差异;（3）探索使用牙齿样本代替股骨颈样本来评估甲基化数据，以提供骨骼健康和年龄的信息;（4）使用骨骼和牙齿样本，检查DNA甲基化用于评估实足年龄的效用，以及（5）确定是否可以基于成像发现进行骨骼脆弱和实际年龄的评估，该奖项反映了NSF的法定使命，并通过评估被认为值得支持使用基金会的知识价值和更广泛的影响审查标准。

The rate of biological aging varies across individuals, being influenced by both genetic and environmental factors. This variation presents challenges in anthropological research and forensic practice for determining how old an individual was when they died based on skeletal measures of aging and frailty. This project leverages epigenetic and imaging data from living and postmortem clinical cohorts to examine the relationship between gene methylation and skeletal frailty and advance methods for understanding patterns of human senescence in the past and present. The results of this research are shared with the general public at the Boston Museum of Science, the Maxwell Museum in Albuquerque, NM, and at the Warren Anatomical Museum at Harvard University. The project supports student science education and training opportunities from elementary school to the postgraduate level (medical and graduate students). Outreach to groups underrepresented or underserved in STEM is planned at the Boston Museum of Science through its events for girls interested in STEM and through the Maxwell Museum’s educational programs.Using advanced imaging methods and epigenetic analysis, this project takes a novel, interdisciplinary approach to further characterize relationships among age, sex, and bone quality/quantity, especially in bone acquired in postmortem contexts. The investigators: (1) provide a methodological proof-of-concept demonstrating that epigenetic modification of genes in DNA derived from both femoral bone and blood samples in osteoporotic living patients is similarly observed in femoral bone and dental samples from skeletal remains, (2) identify any differences in epigenetic modification of the above genes in men and in women; (3) explore using tooth samples instead of femoral neck samples for assessment of methylation data that can provide information about skeletal health and age; (4) examine the utility of DNA methylation for the assessment of chronological age, using bone and dental samples, and (5) determine whether assessments of skeletal frailty and chronological age can be made based on imaging findings, thereby reducing the need for destructive sampling.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.