Mitochondrial free radical theory of aging: who moved my premise?

First proposed by D Harman in the 1950s, the Mitochondrial Free Radical Theory of Aging (MFRTA) has become one of the most tested and well-known theories in aging research. Its core statement is that aging results from the accumulation of oxidative damage, which is closely linked with the release of reactive oxygen species (ROS) from mitochondria. Although MFRTA has been well acknowledged for more than half a century, conflicting evidence is piling up in recent years querying the causal effect of ROS in aging. A critical idea thus emerges that contrary to their conventional image only as toxic agents, ROS at a non-toxic level function as signaling molecules that induce protective defense in responses to age-dependent damage. Furthermore, the peroxisome, another organelle in eukaryotic cells, might have a say in longevity modulation. Peroxisomes and mitochondria are two organelles closely related to each other, and their interaction has major implications for the regulation of aging. The present review particularizes the questionable sequiturs of the MFRTA, and recommends peroxisome, similarly as mitochondrion, as a possible candidate for the regulation of aging.