Fight Aging!

Every cell has its herd of mitochondria. They are the cell's power plants, the descendants of symbiotic bacteria that possess their own DNA and perform a range of vital functions. Unfortunately mitochondria are fragile in comparison to other cellular components and they can cause themselves lasting harm in the course of their normal operation: some forms of damage cannot be repaired by existing cellular processes, and indeed will even spread throughout a cell's herd of mitochondria, causing the entire cell to become dysfunctional. This happens more and more often as the years tick by, and such self-inflicted mitochondrial damage is one of the root causes of aging.

Methods of repair or prevention are under consideration, or their component parts under research, but they don't exist yet, more is the pity. But we know how to remove this contribution to aging - if the funding sources and research community would just step up the pace to get the job done.

So mitochondria are important. They are important, and their ability to function well critical, because they sit right in the middle of many fundamental, vital processes in metabolism. Arguably the most vital of these is managing the transformation of nutrients into chemical energy stores that can be used throughout the cell to power its activities. There is much going on under the hood when it comes to how mitochondria respond to varying nutrient levels, for example. Investigations into the biological mechanisms by which calorie restriction alters the function of metabolism, improves health, and extends life span have resulted in many lines of research that examine protein machinery in mitochondria or the regulation of mitochondrial activity.

To pull one paper at random for the sake of giving some context to that remark, consider research into sirtuins. At least a billion dollars has vanished into sirtuin research over the past decade, in search of ways to recreate at least some of the beneficial effects of calorie restriction without actually restricting dietary intake:

Mitochondrial metabolism, sirtuins, and aging

The sirtuins are a family of proteins that act predominantly as nicotinamide adenine dinucleotide (NAD)-dependent deacetylases. In mammals seven sirtuin family members exist, including three members, Sirt3, Sirt4, and Sirt5, that localize exclusively within the mitochondria. Although originally linked to life-span regulation in simple organisms, this family of proteins appears to have various and diverse functions in higher organisms.

One particular property that is reviewed here is the regulation of mitochondrial number, turnover, and activity by various mitochondrial and nonmitochondrial sirtuins. An emerging consensus from these recent studies is that sirtuins may act as metabolic sensors, using intracellular metabolites such as NAD and short-chain carbon fragments such as acetyl coenzyme A to modulate mitochondrial function to match nutrient supply.

To expand upon this, here is an open access paper that reviews mitochondrial biology and function within the surrounding context of nutrients; even if you only skim it, scroll to the end for the diagram.

Nutrient availability links mitochondria, apoptosis, and obesity

Mitochondria are the dominant source of the cellular energy requirements through oxidative phosphorylation, but they are also central players in apoptosis. Nutrient availability may have been the main evolutionary driving force behind these opposite mitochondrial functions: production of energy to sustain life and release of apoptotic proteins to trigger cell death. Here, we explore the link between nutrients, mitochondria and apoptosis with known and potential implications for age-related decline and metabolic syndromes.

Although ad libitum feeding is standard laboratory practice, it is unlikely to reproduce animals' natural food intake, which is probably nearer to a regimen of calorie restriction (CR). In this regard, since mitochondria evolved to coordinate energy production with food availability, their optimum performance coincides with CR, whereas excess of food intake will compromise mitochondrial energetic capacity.

Thus, we might envisage a scenario where mitochondria are susceptible to apoptosis as their efficiency of energy production, which is linked to nutritional status, declines. In other words, excess food intake will impair respiratory capacity and prime mitochondria for apoptosis, increasing cellular susceptibility to additional stress.

In summary, the nutritional imbalance in western diets leads to mitochondrial dysfunction and higher susceptibility to apoptosis with dramatic consequences for metabolic syndromes such as insulin resistance and liver steatosis. It is already known that caloric restriction protects from several stresses, and it would be interesting to investigate whether cells isolated from mice on different diets show different susceptibilities to apoptotic cell death via the intrinsic pathway and whether this correlates with the mitochondrial respiratory rate. In particular, adult stem cells could be intriguing candidates for further studies, as they show a particular sensitivity to nutrient availability, and their loss contributes to aging.