Department of Animal Sciences and Marine Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
Department of Animal Sciences and Marine Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
Exp Gerontol. 2023 May;175:112154. doi: 10.1016/j.exger.2023.112154. Epub 2023 Mar 20.
Aging is a natural process that determined by a functional decline in cells and tissues as organisms are growing old, resulting in an increase at risk of disease and death. To this end, many efforts have been made to control aging and increase lifespan and healthspan. These efforts have led to the discovery of several anti-aging drugs and compounds such as rapamycin and metformin. Recently, alpha-ketoglutarate (AKG) has been introduced as a potential anti-aging metabolite that can control several functions in organisms, thereby increases longevity and improves healthspan. Unlike other synthetic anti-aging drugs, AKG is one of the metabolites of the tricarboxylic acid (TCA) cycle, also known as the Krebs cycle, and synthesized in the body. It plays a crucial role in the cell energy metabolism, amino acid/protein synthesis, epigenetic regulation, stemness and differentiation, fertility and reproductive health, and cancer cell behaviors. AKG exerts its effects through different mechanisms such as inhibiting mTOR and ATP-synthase, modulating DNA and histone demethylation and reducing ROS formation. Herein, we summarize the recent findings of AKG-related lifespan and healthspan studies and discuss AKG associated cell and molecular mechanisms involved in increasing longevity, improving reproduction, and modulating stem cells and cancer cells behavior. We also discuss the promises and limitations of AKG for delaying aging and other potential applications.
衰老是一个自然过程，随着生物体的衰老，细胞和组织的功能下降，导致疾病和死亡的风险增加。为此，人们做出了许多努力来控制衰老，延长寿命和健康寿命。这些努力导致了几种抗衰老药物和化合物的发现，如雷帕霉素和二甲双胍。最近，α-酮戊二酸（AKG）被引入作为一种潜在的抗衰老代谢物，可以控制生物体的多种功能，从而延长寿命并改善健康寿命。与其他合成抗衰老药物不同，AKG 是三羧酸（TCA）循环的代谢物之一，也称为柠檬酸循环，在体内合成。它在细胞能量代谢、氨基酸/蛋白质合成、表观遗传调控、干性和分化、生育和生殖健康以及癌细胞行为中起着至关重要的作用。AKG 通过不同的机制发挥作用，如抑制 mTOR 和 ATP 合酶、调节 DNA 和组蛋白去甲基化以及减少 ROS 形成。在此，我们总结了 AKG 相关的寿命和健康寿命研究的最新发现，并讨论了 AKG 与增加寿命、改善生殖、调节干细胞和癌细胞行为相关的细胞和分子机制。我们还讨论了 AKG 延缓衰老的前景和局限性以及其他潜在的应用。
