Fight Aging!

I have written on the topic of mitochondrial uncoupling in the past, so back into the archives we go for a quick summary:

Mitochondria are the power plants of your cells: they toil to turn food into ATP, used as fuel by the cell. In recent years, the eye of the research community has turned towards the process of mitochondrial uncoupling, whereby the processing of food is uncoupled from the generation of ATP. The result is less ATP and more energy in the form of heat - this is a part of the temperature regulation process in mammals, for example. It also appears to be important in calorie restriction, and therefore possibly important to longevity and aging.

Research is still in full swing, however, and the vision of how mitochondrial uncoupling fits into the big picture of metabolism and aging is present incomplete. A number of natural uncoupling proteins (such as UCP1, UCP2, and UCP3) as well as manufactured uncoupling drugs like DNP have been investigated with contradictory results.

Some groups have demonstrated extension of life span through alteration of mitochondrial uncoupling in laboratory animals, while others have not. Here is a recent paper:

The discovery of novel uncoupling proteins (UCP2 and UCP3) over 10 years ago heralded a new era of research in mitochondrial uncoupling in a diverse range of tissues. Despite the research vigor, debate stills surrounds the exact function of these uncoupling proteins. For example, the level of uncoupling, the mechanism and mode of action are all under-appreciated at this point in time.

Our recent work has used genetic mouse models to focus on the physiological relevance of UCP2. We have used these mouse models to better appreciate the role UCP2 in human health and disease. In this review we focus on new research showing that UCP2 promotes longevity by shifting a given cell towards fatty acid fuel utilization. This metabolic hypothesis underlying UCP2-dependent longevity suggests that UCP2 is critically positioned to maintain fatty acid oxidation and restrict subsequent oxidative damage allowing sustained mitochondrial oxidative capacity and mitochondrial biogenesis. These mechanisms converge within the cell to boost cell function and metabolism and the net result promotes healthy aging and increased lifespan.

Most views of aging and metabolism that involve mitochondrial function boil down to modes of operation for the mitochondria that produce less biochemical damage over time. This is a very common theme, leaning on the mitochondrial free radical theory of aging. It is yet another reason to focus more resources on bringing mitochondrial repair from the laboratory to the clinic. Repair of damaged mitochondria throughout the body should have a far greater effect on longevity than any change to metabolism that merely slows the accumulation of damage - and such repair technologies are comparatively close to fruition.

Andrews ZB (2010). Uncoupling Protein-2 and the Potential Link Between Metabolism and Longevity. Current aging science PMID: 20158496