Ruden Douglas M
C. S. Mott Center for Human Growth and Development, Institute for Environmental Health Sciences, Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA.
Epigenomics. 2025 Jul 20:1-8. doi: 10.1080/17501911.2025.2533111.
Aging is a complex biological process involving coordinated changes across multiple molecular systems. Traditional reductionist approaches, while valuable, are insufficient to capture the full scope of aging's systemic nature. Multiomics - integrating data from genomics, transcriptomics, epigenomics, proteomics, and metabolomics - provides a comprehensive framework to study aging as an interconnected network. In this Perspective, I explore how multiomic strategies, particularly those leveraging epigenomic and single-cell data, are reshaping our understanding of aging biology. Epigenetic alterations, including DNA methylation and histone modifications, are not only hallmarks but also powerful biomarkers of biological age. I discuss advances in multiomic aging clocks, cross-tissue atlases, and single-cell spatial technologies that decode aging at unprecedented resolution. I also build on a prior review I wrote with colleagues, Epigenomics. 2023;15(14):741-754, which introduced the concept of pathological epigenetic events that are reversible (PEERs) - epigenetic alterations linked to early-life exposures that predispose to aging and disease but may be therapeutically modifiable. This Perspective examines how PEERs and multiomics intersect to inform biomarkers, geroprotective interventions, and personalized aging medicine. Finally, I highlight integration challenges, ethical concerns, and the need for standardization to accelerate clinical translation. Together, these insights position multiomics as a central pillar in the future of aging research.
衰老 是一个复杂的生物学过程,涉及多个分子系统的协同变化。传统的还原论方法虽然有价值,但不足以全面捕捉衰老的系统性本质。多组学——整合来自基因组学、转录组学、表观基因组学、蛋白质组学和代谢组学的数据——提供了一个全面的框架,将衰老作为一个相互关联的网络来研究。在这篇观点文章中,我探讨了多组学策略,特别是那些利用表观基因组和单细胞数据的策略,如何正在重塑我们对衰老生物学的理解。表观遗传改变,包括DNA甲基化和组蛋白修饰,不仅是生物学衰老的标志,也是强大的生物标志物。我讨论了多组学衰老时钟、跨组织图谱和单细胞空间技术的进展,这些技术以前所未有的分辨率解码衰老。我还基于我与同事共同撰写的一篇先前的综述《表观基因组学》(Epigenomics. 2023;15(14):741 - 754),该综述引入了可逆的病理性表观遗传事件(PEERs)的概念——与早期生活暴露相关的表观遗传改变,这些暴露易导致衰老和疾病,但可能通过治疗进行调节。这篇观点文章探讨了PEERs与多组学如何相互交叉,以为生物标志物、老年保护干预措施和个性化衰老医学提供信息。最后,我强调了整合挑战、伦理问题以及标准化的必要性,以加速临床转化。总之,这些见解将多组学定位为衰老研究未来的核心支柱。