Mitochondria and aging

From Santa Fe Institute Event Wiki

Mitochondria are abundant cellular organelles, whose primary function is to provide the cell with ATP by burning food (i.e. combining it with oxygen we breathe). Mitochondria possess their own 16kb-long DNA inherited from ancient symbiotic bacteria and densely packed with genes coding for a few essential polypeptides and RNA. Mitochondrial environment apparently is not safe for their DNA and, as we age, mitochondrial DNA (mtDNA) accumulates high levels of somatic mutations. The hypothesis that these mutations are involved in aging has been suggested decades ago but it remains controversial, primarily because of the insufficiency of reliable data regarding abundance and fine spatial distribution of mutations in aged tissues. Recently, this hypothesis suffered unprecedented swings of credibility as data from "mtDNA mutator" transgenic mice were first interpreted to strongly support the hypothesis and later to equally strongly reject it. The conclusions of these studies, however, may be confounded by the differences in the spatial-temporal distribution of mutations between normal and mutator mouse and by the murine-human differences. Several models of how mtDNA mutations may affect aging that take into consideration the different types of mutations (deletions and point mutations), cell-type specificity (mutations can concentrate in rare but critical cell types within tissue), and clonal expansion of mutations within individual cells, will be discussed. It appears that mtDNA mutations are either driving certain aspects of aging or are at the verge of doing so. It is striking that mutations in a genome five orders of magnitude smaller than the nuclear genome ever get any close to being of significance. This paradox may stem from the fact that an organism has no incentive to perfect any of its repair systems beyond the point of their relevance to survival, which might have kept the levels of mtDNA mutations at just bearable levels for historic human life span. Recent rapid increase in human longevity and rapid accumulation of mtDNA mutations with age might have enabled mtDNA mutations to gain significance in human aging.