Anti-Aging: How Science Says Your Mitochondria Plays a Role

Today, there are several promising anti-aging strategies including exercise, fasting, and taking certain drugs (like Type Two Diabetes drug Metformin).

For example, one of the latest nutrition fads is in regards to eating Kale. Why?

Kale, like other leafy greens, is very high in antioxidants. These antioxidants prevent oxidative stress from – free radicals; molecules formed when we convert food into energy or when we exercise. The same process of reduction and oxidation that gives us energy can damage cells, and that damage has been linked to everything from cancer to Parkinson’s disease.

Antioxidants came to public attention in the 1990s, when scientists began to understand that free radical damage was involved in the early stages of artery-clogging atherosclerosis and other chronic diseases. Some studies showed that people with low intakes of antioxidant-rich fruits and vegetables were at greater risk for developing these chronic conditions than were people who ate plenty of these fruits and vegetables.

The media, and the supplement and food industries began to hype the benefits of “antioxidants.” Frozen berries, green tea, and other foods labeled as being rich in antioxidants began popping up in stores. Before the clinical trial results were in, supplement makers touted the disease-fighting properties of all sorts of antioxidants.

But more than a decade ago, Research by Professor Michael Ristow out of Zurich suggests that while exercise increased insulin sensitivity in a study control group, intake of some antioxidant supplements offset these exercise-induced gains in people’s own antioxidant defense.

According to Caltech Biology Professor Bruce A. Hay some research indicates that taking a very high dose antioxidant supplement before you hit the gym could actually be having a harmful effect – lessening the gains in muscle strength from your workout.

According to Professor Hay, the cell damage or oxidative damage is a function of ATP production that happens in your mitochondria cells when you exercise your muscles during exercise. But things like taking large amounts of antioxidants don’t seem to actually help with reducing cell damage, and oftentimes, actually make the situation worse.

A Different Approach to Anti-Aging: Up Leveling Mitochondria Quality Control
Professor Hay and his lab are taking a different approach to anti-aging, that has to do with reversing the damage to the mitochondria that are responsible for ATP production in the body.

Mitochondria are the organelles that supply a cell’s energy, harbor their own mitochondrial DNA (mtDNA) and mutations there can have devastating consequences such as muscle wasting. There are hundreds to thousands of mitochondria in each of our cells, and mitochondria produce most of our bodies’ ATP. They are always being created and destroyed, and they are also always fusing together (mitochondrial fusion) and breaking apart (mitochondrial fission). The reason they fuse is to combine their contents to maximize ATP production.

The mutations in mitochondria are a core reason for aging. As we age, more of our mitochondria genomes develop mutations and mutant mitochondria when they exceed a certain threshold, perhaps about 70% – start to cause effects of aging like muscle wasting.

Professor Hay and his team have done work (1) showing that when they stimulate mitophagy – a process in which mutant mitochondria are selected, tagged, and then shipped to organelles that break them down – healthy mitochondria substitute in place of dysfunctional mitochondria, rejuvenating cellular function.

Professor Hay has developed a model for mitochondrial DNA mutation accumulation in muscle and is using this system to identify molecules that can promote the selective removal of mutant mitochondrial DNA, a form of quality control.

“What we found which is really exciting,” explains Professor Hay “is that if we simply stimulate the autophagy [autophagy is the body’s self-eating process, for removing cellular debris] process which is normally occurring at a basal level in the cells, or if we increase the activity of PINK and Parkin, either one of those modest increases in activity can drive down the level of mutant genomes from about 75% to about 4% or 5%.”

“That’s really a remarkable decrease,” says Hay. “Because we know that you only show the consequences of having mutant mtDNA if you have a high frequency, something like 75%. “

“One of the challenges is that the body is most likely maximized or designed for ATP or energy production,” explains Hay. “From an evolutionary standpoint, it makes sense that we would be designed to be able to produce bursts of energy to run away from a lion.”

Combining Upleveling Mitochondria Repair with Five-Day Fasting/ Autophagy
The five-day fasting mimicking diet that is being investigated by Dr. Valter Longo’s lab at USC is also showing remarkable results, in terms of turning on the body’s ability to repair and or rejuvenate mitochondria.

No research or collaboration with Dr. Longo’s lab has been done to date. But Professor Hay says he could see how timing a fasting mimicking diet to coincide with the treatment of upleveling the mitochondria pathway in the body, could deliver a promising powerful combination.

Today the exciting opportunity according to Professor Hay is if the process of eliminating mutant mitochondrial DNA, could somehow be increased – or sped up. Up leveling the pathway for mitochondrial DNA quality control could reverse one kind of aging condition, the accumulation of mutant genomes of mitochondria. Our bodies already contain this mitochondrial pathway, but it’s not activated to maximize quality control. Our mitochondria are focused on turning food into energy and ATP production.

Not Genetic Engineering

Professor Hay explains that the focus is not so much on genetic engineering in the classic sense of put a new genes into people. His lab is working on gently tweaking a pathway using small molecules, components that normally would carry out the quality control but don’t because they’re usually tied up doing other things.

The goal is to transiently up regulate the mitochondria quality control process in an otherwise healthy patient – to make that house cleaning process work a little harder for a while.

In the future, fighting aging might be less about drinking that Kale smoothie, and more about taking a pill to repair damaged Mitochondrial DNA – and increase your energy and ATP production.

Professor Hay is collaborating with the UCLA lab of Ming Guo, PhD screening for drugs that could some day engineer mitochondrial DNA (mtDNA) “housecleaning” in human patients. The hope is to develop mitochondrial quality control boosting drugs or treatments to slow aging and prevent many diseases of aging like Alzheimer’s, Parkinsons, diabetes, and muscle wasting.