Johnson Adiv A, Shokhirev Maxim N
Tally Health, New York, NY, USA.
Biogerontology. 2025 Jun 18;26(4):121. doi: 10.1007/s10522-025-10265-4.
Aging biomarkers that predict age given methylomic data are referred to as epigenetic aging clocks. While the earliest, first-generation clocks were exclusively trained to predict chronological age, more recent next-generation models have been explicitly trained to associate with health, lifestyle, and/or age-related outcomes. Although these next-generation models have been trained using distinct approaches and techniques, existing evidence indicates that they associate with a greater number of health and disease signals than first-generation clocks. Moreover, they are often more predictive of age-related outcomes and appear more responsive to interventions. In this work, we provide definitions for first- versus next-generation clocks and discuss the potential merits of further dividing next-generation clocks into sub-categories. In addition, we summarize existing next-generation epigenetic aging clocks, including how they were trained and how they can be accessed. Given the relative value of interventional data over observational data, we comprehensively tabulate existing literature documenting the ability of an intervention to influence at least one epigenetic aging clock. While we acknowledge that the decision to a use a specific clock is ultimately dependent on the research application and goal, current evidence suggests that next-generation models should be generally prioritized for health-oriented association and interventional studies.
根据甲基化组数据预测年龄的衰老生物标志物被称为表观遗传衰老时钟。虽然最早的第一代时钟专门用于预测实足年龄,但最近的下一代模型已被明确训练用于关联健康、生活方式和/或与年龄相关的结果。尽管这些下一代模型采用了不同的方法和技术进行训练,但现有证据表明,它们与比第一代时钟更多的健康和疾病信号相关联。此外,它们通常对与年龄相关的结果更具预测性,并且似乎对干预措施更敏感。在这项工作中,我们为第一代和下一代时钟提供了定义,并讨论了将下一代时钟进一步细分为子类别的潜在优点。此外,我们总结了现有的下一代表观遗传衰老时钟,包括它们的训练方式以及如何获取。鉴于干预数据相对于观察数据的相对价值,我们全面列出了现有文献,记录了干预措施影响至少一个表观遗传衰老时钟的能力。虽然我们承认使用特定时钟的决定最终取决于研究应用和目标,但目前的证据表明,在以健康为导向的关联和干预研究中,通常应优先考虑下一代模型。