Does Modulation of an Epigenetic Clock Define a Geroprotector?

There is growing interest in the development of interventions (e.g., drugs, diets, dietary supplements, behavioral therapies, etc.) that can enhance health during the aging process, prevent or delay multiple age-related diseases, and ultimately extend lifespan. However, proving that such ‘geroprotectors’ do what they are hypothesized to do in relevant clinical trials is not trivial. We briefly discuss some of the more salient issues surrounding the design and interpretation of clinical trials of geroprotectors, including, importantly, how one defines a geroprotector. We also discuss whether emerging surrogate endpoints, such as epigenetic clocks, should be treated as primary or secondary endpoints in such trials. Simply put, geroprotectors should provide overt health and disease prevention benefits but the time-dependent relationships between epigenetic clocks and health-related phenomena are complex and in need of further scrutiny. Therefore, studies that enable understanding of the relationships between epigenetic clocks and disease processes while simultaneously testing the efficacy of a candidate geroprotector are crucial to move the field forward.

人们对开发干预措施（例如药物、饮食、膳食补充剂、行为疗法等）的兴趣日益浓厚，这些干预措施能够在衰老过程中增进健康，预防或延缓多种与年龄相关的疾病，并最终延长寿命。然而，在相关临床试验中证明这类“抗衰老保护剂”确实能发挥其假设的作用并非易事。我们简要讨论了围绕抗衰老保护剂临床试验的设计和解读的一些较为突出的问题，重要的是包括如何定义抗衰老保护剂。我们还讨论了新兴的替代终点（如表观遗传时钟）在这类试验中应被视为主要终点还是次要终点。简而言之，抗衰老保护剂应该提供明显的健康和疾病预防益处，但表观遗传时钟与健康相关现象之间的时间依赖关系是复杂的，需要进一步仔细研究。因此，能够理解表观遗传时钟与疾病过程之间的关系，同时测试候选抗衰老保护剂功效的研究对于推动该领域的发展至关重要。