Many longevity mutations discovered in lower animals such as nematodes involve alterations to mitochondrial function - which only reinforces the apparent importance of mitochondria in determining life span. Mitochondria swarm within cells, working to produce the chemical energy stores used to power cellular operations. In doing so they emit reactive oxygen species, however, that can cause all sorts of harm to the molecular machinery of a cell if not neutralized by a cell's native antioxidants. It is damage to mitochondrial DNA, however, that seems to be one of the root causes of degenerative aging, via a Rube Goldberg sequence of consequences that causes cells to become dysfunctional mass exporters of reactive, harmful molecules.
From a practical therapy standpoint, the research community should be working on ways to repair, replace, or back up mitochondrial DNA in our cells if we want this contribution to aging to go away. That work is very poorly funded, however, in comparison to the benefits it might deliver. Meanwhile, examination of longevity mutations in lower animals continues to reinforce the fact that this is an important direction for therapies to treat and reverse aging.
Some mitochondrial longevity mutations work via hormesis; they cause a slight increase in the level of emitted reactive oxygen species, which in turn causes the cell to react with increased housekeeping and repair activities, resulting in a net gain - less damage over the long term translates into slower aging. Other mutations lower the level of emitted reactive oxygen species, which again means less damage over the long term. Yet more mitochondrial mutations extend life in less obvious ways, or cause mitochondrial dysfunction that appears at the high level to be broadly similar to that of longevity mutants, yet reduces life span. Once you start digging in to the mechanisms of the mitochondrial interior - the electron transport chain with it's multiple complexes - it's all far from simple
Here is an example of research into the mechanisms of mitochondrial longevity mutations in nematode worms:
Many Caenorhabditis elegans mutants with dysfunctional mitochondrial electron transport chain are surprisingly long lived. Both short-lived (gas-1(fc21)) and long-lived (nuo-6(qm200)) mutants of mitochondrial complex I have been identified. However, it is not clear what are the pathways determining the difference in longevity.
We show that even in a short-lived gas-1(fc21) mutant, many longevity assurance pathways, shown to be important for lifespan prolongation in long-lived mutants, are active. Beside similar dependence on alternative metabolic pathways, short-lived gas-1(fc21) mutants and long-lived nuo-6(qm200) mutants also activate hypoxia-inducible factor-1α (HIF-1α) stress pathway and mitochondrial unfolded protein response (UPRmt).
The major difference that we detected between mutants of different longevity is in the massive loss of complex I accompanied by upregulation of complex II levels, only in short-lived, gas-1(fc21) mutant. We show that high levels of complex II negatively regulate longevity in gas-1(fc21) mutant by decreasing the stability of complex I. Furthermore, our results demonstrate that increase in complex I stability, improves mitochondrial function and decreases mitochondrial stress, putting it inside a "window" of mitochondrial dysfunction that allows lifespan prolongation.