Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, 117456, Singapore.
Centre for Healthy Longevity, National University Health System (NUHS), Singapore, Singapore.
Geroscience. 2023 Oct;45(5):2897-2907. doi: 10.1007/s11357-023-00813-6. Epub 2023 May 23.
Targeting molecular processes of aging will enable people to live healthier and longer lives by preventing age-related diseases. Geroprotectors are compounds with the potential to increase healthspan and lifespan. Even though many of them have been tested in animal models, the translation to humans is limited. Alpha-Ketoglutarate (AKG) has been studied widely in model animals, but there are few studies testing its geroprotective properties in humans. ABLE is a double blinded placebo-controlled randomized trial (RCT) of 1 g sustained release Ca-AKG versus placebo for 6 months of intervention and 3 months follow up including 120 40-60-year-old healthy individuals with a higher DNA methylation age compared to their chronological age. The primary outcome is the decrease in DNA methylation age from baseline to the end of the intervention. A total of 120 participants will be randomized to receive either sustained release Ca-AKG or placebo. Secondary outcomes include changes in the inflammatory and metabolic parameters in blood, handgrip strength and leg extension strength, arterial stiffness, skin autofluorescence, and aerobic capacity from baseline to 3 months, 6 months, and 9 months. This study will recruit middle-aged participants with an older DNA methylation age compared to their chronological age, and test whether supplementation with Ca-AKG can reduce DNA methylation age. This study is unique in its inclusion of biologically older participants.
靶向衰老的分子过程将通过预防与年龄相关的疾病使人们更健康、更长寿。 衰老抑制剂是具有增加健康寿命和寿命潜力的化合物。 尽管它们中的许多已经在动物模型中进行了测试，但将其转化为人类仍然有限。 α-酮戊二酸（AKG）在模型动物中得到了广泛研究，但在人类中测试其抗衰老特性的研究很少。 ABLE 是一项为期 6 个月的干预和 3 个月随访的双盲安慰剂对照随机试验（RCT），比较了 1 克缓释 Ca-AKG 与安慰剂的疗效，纳入了 120 名 40-60 岁的健康个体，与他们的实际年龄相比，他们的 DNA 甲基化年龄更高。 主要结局是从基线到干预结束时 DNA 甲基化年龄的下降。 总共将有 120 名参与者被随机分配接受缓释 Ca-AKG 或安慰剂。 次要结局包括从基线到 3 个月、6 个月和 9 个月时血液中的炎症和代谢参数、握力和腿部伸展力量、动脉僵硬、皮肤自发荧光和有氧能力的变化。 该研究将招募与实际年龄相比 DNA 甲基化年龄较大的中年参与者，并测试 Ca-AKG 补充是否可以降低 DNA 甲基化年龄。 该研究的独特之处在于纳入了生物学上年龄较大的参与者。
