The mitochondrial theory of aging: do damaged mitochondria accumulate by delayed degradation?

The mitochondrial theory of aging states that the slow accumulation of impaired mitochondria is the driving force of the aging process. In recent years, this theory has gained new support with the discovery of age-related mitochondrial DNA deletions. However, the underlying mechanism of the accumulation of defective mitochondria remained unclear. This has changed recently with the proposal of de Grey that damaged mitochondria have a decreased degradation rate. The resulting increase in biological half-life would be a strong selection advantage leading to the accumulation of defective mitochondria. In this article, I summarize current ideas on how damaged organelles can build up in a cell as well as the shortcomings of these ideas. Then the new hypothesis and its justification are described. It appears that de Grey's hypothesis is a very promising concept that elegantly solves inconsistencies of current models and is in accordance with experimental findings.