Levy Joshua J, Diallo Alos B, Saldias Montivero Marietta K, Gabbita Sameer, Salas Lucas A, Christensen Brock C
Department of Pathology and Laboratory Medicine, Cedars Sinai Medical Center, Los Angeles, CA, USA.
Department of Computational Biomedicine, Cedars Sinai Medical Center, Los Angeles, CA, USA.
Epigenomics. 2025 Jan;17(1):49-57. doi: 10.1080/17501911.2024.2432854. Epub 2024 Nov 25.
Over the past century, human lifespan has increased remarkably, yet the inevitability of aging persists. The disparity between biological age, which reflects pathological deterioration and disease, and chronological age, indicative of normal aging, has driven prior research focused on identifying mechanisms that could inform interventions to reverse excessive age-related deterioration and reduce morbidity and mortality. DNA methylation has emerged as an important predictor of age, leading to the development of epigenetic clocks that quantify the extent of pathological deterioration beyond what is typically expected for a given age. Machine learning technologies offer promising avenues to enhance our understanding of the biological mechanisms governing aging by further elucidating the gap between biological and chronological ages. This perspective article examines current algorithmic approaches to epigenetic clocks, explores the use of machine learning for age estimation from DNA methylation, and discusses how refining the interpretation of ML methods and tailoring their inferences for specific patient populations and cell types can amplify the utility of these technologies in age prediction. By harnessing insights from machine learning, we are well-positioned to effectively adapt, customize and personalize interventions aimed at aging.
在过去的一个世纪里,人类寿命显著延长,但衰老的必然性依然存在。反映病理恶化和疾病的生物学年龄与指示正常衰老的实际年龄之间的差异,推动了先前的研究,这些研究聚焦于确定相关机制,以便为逆转与年龄相关的过度恶化以及降低发病率和死亡率的干预措施提供依据。DNA甲基化已成为年龄的重要预测指标,促使表观遗传时钟的发展,这种时钟能够量化超出给定年龄通常预期的病理恶化程度。机器学习技术为增强我们对衰老生物学机制的理解提供了有前景的途径,通过进一步阐明生物学年龄和实际年龄之间的差距来实现这一点。这篇观点文章审视了当前表观遗传时钟的算法方法,探讨了利用机器学习从DNA甲基化进行年龄估计,并讨论了如何完善机器学习方法的解释,以及针对特定患者群体和细胞类型调整其推断,从而扩大这些技术在年龄预测中的效用。通过利用机器学习的见解,我们能够很好地有效地调整、定制和个性化针对衰老的干预措施。