The Mitochondrial Free Radical Theory of Aging (MRFTA) is the most influential approach in the aging studies. It was established by Bert when studying how highly concentrated oxygen affects warm-blooded animals. The study revealed that ambient temperature was responsible for the varying oxygen toxicity in cold-blooded animals. Various studies followed later, including Herman’s proposal in 1996. According to the concept, aging and related degenerative diseases are caused by harmful side attacks of free radicals on the components of cells and the connected tissues. In the 1970s, Herman developed the theory. He suggested that free radical originate from mitochondria. The MRFTA theory has since been influenced over time by various studies. Jacob Schor, in his article, “A New Look at the Free Radical Theory of Aging,” explores the evolution of the MRFTA.
The MRFTA theory has intensively explored the effects of antioxidants on longevity. Studies indicated that antioxidants only increased the durability of the animals whose lifespan was less than three years because the antioxidant level of the tissues of the animals with a longer lifespan was lower compared to that of short-lifespan animals. The association was negative even after adding dietary antioxidants. These findings implied that antioxidants protected the animal from premature death when living conditions were not favorable. Therefore, antioxidants have the potential to protect short-lived animals when they are subjected to less-than-optimal conditions,such as chemical and oxidative insults. However, they do not extend longevity.
The mentioned findings spurred a new approach to aging, which hypothesized that the mitochondria ROS production plays a critical role in aging the process. Since the production of antioxidants requires some energy, long-lived species adapt by limiting the production of ROS. Studies then focused on examining the association between the mtROSp and longevity; low mtROSp increases longevity. The sites in which ROS production occurs are close to the mitochondria’s DNA. The ROS produced near the DNA are responsible for greater durability. These findings raised questions on how mtROSp, which is localized, has a significant influence on longevity while systematic antioxidants have minimal effect. Schor explains that damage to the mtROSp determines age yet antioxidants have limited influence on locally produced ROS. Therefore, while antioxidants can have a broad protective effect, aging occurs locally.
The MRFTA theory associates longevity with fatty acid saturation. It has been consistently found that unsaturation levels of fatty acid in cellular membranes have a direct effect on longevity. As species grow older, the levels of fatty acids decrease. Similarly, the smaller the degree of unsaturated fatty acids, the more the membranes become resistant to lipid peroxidation. Lipid peroxidation is a highly toxic reaction responsible for the production of mutagenic metabolites within cells.
Recently, MRFTA incorporated the concept of the effect calorie-restricted meals and methionine depletion on longevity. The existing knowledge establishes that consuming fewer calories can extend longevity in many species. Most studies conducted in this line of research have, however, focused on mitochondrial oxidative stress. It has been found that the source of calories matters, therefore, it is important to consider the source of calories is restricted. Recent data has also revealed that methionine plays a significant role in greater longevity in calorie-restricted diets. Conclusively, although MRFTA has been widely accepted, it cannot be fully applied in practice since most versions of the theory have been disapproved.