The Role of Mitochondria in Longevity and Healthspan

An editorial from the Longevity and Healthspan journal:

Mitochondria are indispensable for aerobic life. Depending on the tissue and species, they normally occupy 2-20% of the volume of a cell, and it can be up to 50%. They have their own DNA and undergo constant motion, fusion and fission. They provide the cell with ATP formed during the oxidation of carbohydrate, proteins and fats and are involved in a range of metabolic pathways. They help regulate cellular calcium levels, trigger apoptosis, and can generate reactive oxygen species that are used in cellular signalling and can cause oxidative damage.

The role of mitochondria in aging and disease remains contentious more than 40 years after the mitochondrial free radical theory of aging was first proposed. The hallmark of a useful hypothesis is that it stimulates further work and drives progress in its field. The free radical theory of aging has certainly done that since Harman proposed it in its general form in 1956 and in a more mitochondrially-oriented form in 1972. This theory proposes that the primary cause of aging is mitochondrial production of free radicals and the mitochondrial damage that ensues. The evidence that has been gathered over the years has led to adjustments and refinements in the formulation of the hypothesis as different authors have attempted to articulate it more precisely and to square it with experimental observations; as a result there have been numerous updates and overviews. Many of these have been very influential. However, the perspective has become increasingly critical as the predicted beneficial effects of many antioxidant treatments and genetic manipulations have failed to materialise.

Where does that leave us today? On the one hand, many of the manipulations that should decrease aging and increase longevity according to the classical versions of the mitochondrial free radical theory of aging have failed to do so, implying that the theory is wrong, or at best deeply flawed. On the other hand, some of these manipulations have been very successful, implying that that the theory refracts some underlying reality and still has significant value as a guide to thought and experiment.



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