Linking Telomere Shortening and Mitochondrial Damage?

I bumped into a great paper just the other day that illustrates the rewarding side of keeping up with scientific publications. Every so often you see something that might just be very important if correct, linking together disparate but significant areas of exploration and indicating that the way forward might be more straightfoward than imagined. The mapping of complex systems often looks like this - sail the rivers first, and then find the roads between. All becomes clear in hindsight, and those moments at which clarity arrives are easily remembered.

In any case, have a look at this PloS Biology publication claiming telomere shortening to rest on the shoulders of mitochondrial damage:

After a limited number of cell divisions, somatic cells lose the capacity for proliferation, called cellular replicative senescence. Senescence, which is triggered by the loss of DNA sequences at the ends of chromosomes (telomeres), is often seen as an example of a regular “biological clock.” However, cell senescence is heterogeneous, with large differences in lifespan between individual cell lineages. This heterogeneity is clearly related to stress, specifically oxidative stress. It was not known, however, whether stress-induced “premature” senescence involves telomeres or is caused by telomere-independent DNA damage responses. Mitochondria are the most important source of reactive oxygen species (ROS) in cells under physiological conditions. We found that mitochondrial function deteriorated while cells approached senescence, leading to increased ROS production. Delaying mitochondrial dysfunction led to postponed replicative senescence and slowing of telomere shortening. Prematurely senescing cells sorted out of young cultures displayed mitochondrial dysfunction, increased oxidative stress, and short telomeres. We propose that replicative telomere-dependent senescence is not “clocked,” but rather is a stochastic process triggered largely by random mitochondrial dysfunction.

We know that mitochondrial damage is tied to aging via mechanisms such as the production of damaging free radicals such as ROS - and that some researchers are working on solutions, such as the ability to replace all mitochondrial DNA in the body via protofection. We also know that progessive telomere shortening is tied to aging and age-related disease, and a number of different groups are working on strategies to safely lengthen telomeres.

There is strong evidence to believe that "tied to aging" in this context means "contributes to aging as a cause." Remember that aging is no more than an accumulation of damage in biochemical systems; when we look at these changes that take place with aging, we are looking at damage. This paper offers the possibility that if we repair or prevent the progressive accumulation of mitochondrial degeneration and damage, then the telomeres will take care of themselves - if the results are replicated, of course.

Keep an eye on the funding for research into cures for mitochondrial diseases in the next few years; the mainstream funding system is steered by regulation into supporting only the search for cures for specific named conditions, but the technologies employed in repairing dysfunctional, malformed mitochondria may also be applied to age-damaged mitochondria.

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