Biphasic Modeling of Mitochondrial Metabolism Dysregulation during Aging

Organismal aging is classically viewed as a gradual decline of cellular functions and a systemic deterioration of tissues that leads to an increased mortality rate in older individuals. According to the prevailing theory, aging is accompanied by a continuous and progressive decline in mitochondrial metabolic activity in cells. However, the most robust approaches to extending healthy lifespan are frequently linked with reduced energy intake or with lowering of mitochondrial activity. While these observations appear contradictory, recent work and technological advances demonstrate that metabolic deregulation during aging is potentially biphasic. In this Opinion we propose a novel framework where middle-age is accompanied by increased mitochondrial activity that subsequently declines at advanced ages.