Feng Zhaoyang, Hanson Richard W, Berger Nathan A, Trubitsyn Alexander
Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Oncotarget. 2016 Mar 29;7(13):15410-20. doi: 10.18632/oncotarget.7645.
Aging is characterized by progressive loss of cellular function and integrity. It has been thought to be driven by stochastic molecular damage. However, genetic and environmental maneuvers enhancing mitochondrial function or inhibiting glycolysis extend lifespan and promote healthy aging in many species. In post-fertile Caenorhabditis elegans, a progressive decline in phosphoenolpyruvate carboxykinase with age, and a reciprocal increase in pyruvate kinase shunt energy metabolism from oxidative metabolism to anaerobic glycolysis. This reduces the efficiency and total of energy generation. As a result, energy-dependent physical activity and other cellular functions decrease due to unmatched energy demand and supply. In return, decrease in physical activity accelerates this metabolic shift, forming a vicious cycle. This metabolic event is a determinant of aging, and is retarded by caloric restriction to counteract aging. In this review, we summarize these and other evidence supporting the idea that metabolic reprogramming is a driver of aging. We also suggest strategies to test this hypothesis.
衰老的特征是细胞功能和完整性的逐渐丧失。人们一直认为它是由随机的分子损伤驱动的。然而，增强线粒体功能或抑制糖酵解的遗传和环境调控措施可延长许多物种的寿命并促进健康衰老。在生育后期的秀丽隐杆线虫中，磷酸烯醇式丙酮酸羧激酶随年龄增长而逐渐下降，丙酮酸激酶分流增加，能量代谢从氧化代谢转变为无氧糖酵解。这降低了能量产生的效率和总量。结果，由于能量需求和供应不匹配，依赖能量的身体活动和其他细胞功能下降。反过来，身体活动的减少加速了这种代谢转变，形成恶性循环。这种代谢事件是衰老的一个决定因素，热量限制可减缓这一过程以对抗衰老。在本综述中，我们总结了这些以及其他支持代谢重编程是衰老驱动因素这一观点的证据。我们还提出了检验这一假设的策略。
