The Comparative Biology of Mitochondrial Function and the Rate of Aging

Abstract

The mitochondrial hypothesis of aging evolved from the rate-of-living theory. That theory posited that the rate of aging was largely determined by the rate of energy expenditure. The mechanistic link between energy expenditure and aging was hypothesized to be oxidative stress. As both energy expenditure and reactive oxygen species (ROS) centered on the mitochondria that organelle became a central focus of aging research. Until about the turn of the 21^st century available evidence largely supported the efficiency of mitochondrial function as a key contributor to aging. However as methods for investigating mitochondrial oxidant production and tissue level oxidative damage improved, evidentiary support for the theory weakened. Recently, direct disruption of mitochondrial function has been shown not to shorten life or health as expected, but in many cases in multiple laboratory species disrupted mitochondrial function has lengthened life, sometimes without apparent tradeoffs. Does this mean that mitochondrial function plays no role in aging as had been posited for many years? One key consideration is that experiments under laboratory conditions can be misleading about physiological processes that occur in the uncertain conditions of nature. Before we discard the mitochondrial hypothesis of aging, more field experiments targeted at that hypothesis need to be performed. Fortunately, emerging technology is making such experiment more possible than ever before.