Epigenetic processes and biological senescence in humans

生物衰老的速度因个体而异，受遗传和环境因素的影响。这种变异在人类学研究和法医实践中提出了挑战，无法根据骨骼对衰老和虚弱的测量来确定一个人死亡时的年龄。该项目利用活的和死后的临床队列的表观遗传学和成像数据来研究基因甲基化和骨骼脆弱之间的关系，并提出了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尔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(医学和研究生)的学生科学教育和培训机会。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Maxwell博物馆的教育项目，向STEM中代表不足或服务不足的群体进行推广。该项目使用先进的成像方法和表观遗传学分析，采用一种新颖的跨学科方法来进一步表征年龄、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方面。研究人员：(1)提供方法论的概念验证，证明来自骨质疏松症活体患者的股骨和血液样本的DNA中的基因的表观遗传修饰在股骨和来自骨骼残骸的牙齿样本中类似地被观察到；(2)确定上述基因的表观遗传修饰在男性和女性中的任何差异；(3)探索使用牙齿样本代替股骨颈样本来评估甲基化数据，以提供关于骨骼健康和年龄的信息；(4)使用骨骼和牙齿样本，检查DNA甲基化用于评估年代年龄的效用，以及(5)确定是否可以基于成像结果对骨骼脆性和年代年龄进行评估，从而减少破坏性采样的需要。该奖项反映了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。

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.