Thursday, November 21, 2019

Mitochondrial Aging Theory

Why do we age? With all the advancements we have made in medical science, why aren't we able to extend our time here on Earth and live a lot longer? One theory is that aging is caused by a decline in mitochondrial function. Mitochondria are the powerhouses of the cell, their proteins converting nutrients into chemical energy that we need called ATP. The interesting thing about mitochondria is that they are actually another completely unique organism living within each of our cells, and there is not just one of them per cell, but up to hundreds or even thousands of mitochondria in each cell.

When we are young and healthy, everything works at its optimal best, but as we age we gradually lose mitochondrial function and have less and less ATP available. The theory is that as our ability to make energy decreases, we age and increasingly experience degenerative diseases.

Mitochondria were once free-living organisms that joined our cells in a symbiotic relationship about two billion years ago. They were originally alpha-proteo-bacteria that can still be found living freely throughout the world. The important thing is that these mitochondria have their own DNA. They brought their own genome with them when they merged with our cells. Many of the genes of their DNA have been transferred to the nucleus of our cells, so really we are just a mesh-mash of two species living together. 

The genomes of the mitochondria and our nucleus are not the same and need to constantly communicate with each other to maintain their coexistence and keep things functioning in a healthy manner.  One of the problems that may be a factor in our aging is that these two bodies lose some of their ability to communicate with each other. Throughout life our mitochondria generate free radicals during metabolism that damage our enzymes and DNA, and especially the DNA within the mitochondria, so we begin to lose the code within our mesh-mash of mitochondrial DNA. We get mutations and big deletions that accumulate over time. If we could slow down this damage to our DNA, the idea is that perhaps we could delay aging, be healthier, and have a longer life.

Since this theory was proposed more than half a century ago, we really have not had much success in slowing free radical damage to DNA, unfortunately. No matter how many antioxidants you take, they really do not have much of an impact on reducing DNA damage. On the flip side, more recent evidence suggests that free radicals may actually be beneficial on net and actually extend life span.  So the science is far from settled in regard to free radicals.

Recent research is demonstrating that if you catch aging early enough, it may be reversible to some degree. Approaching the aging issue by attempting to improve communication between the nucleus and the mitochondria has shown more promise than attempting to manage free radicals in holding back the tide of aging. Findings in 2013 showed that perhaps one of the main breakdowns of communication results from the nucleus believing it is not getting enough energy from the mitochondria anymore, so it slows sending signals to the mitochondria to generate more energy. It is believed that this entire winding down cycle begins with the loss of a small molecule called NAD (nicotinamide adenine dinucleotide) that is critical for cells to maintain their communication.

When NAD levels were restored to youthful levels in test studies with mice, their mitochondria were revved up again, remarkably within a week, but there was no evidence that muscle strength was improved. While there is promising test-tube data and animal research regarding NAD boosters, no human clinical results on them have yet been published. Supplements containing nicotinamide riboside, or NR, a precursor to NAD, may be able to boost NAD levels, but the jury is still out.

The increasing number of NAD findings lead us to an ongoing story about certain enzymes called sirtuins, which have been implicated as key players in conferring the longevity and health benefits of calorie restriction. Resveratrol, a wine ingredient, is thought to rev up one of the sirtuins, SIRT1, which appears to help protect mice on high doses of resveratrol from the ill effects of high-fat diets. A slew of other health benefits have been attributed to SIRT1 activation as well.

NAD fuels the activity of sirtuins, including SIRT1 - the more NAD there is in cells, the more that SIRT1 does beneficial things. One of those things is to induce formation of new mitochondria. NAD can also activate another sirtuin, SIRT3, which is thought to keep mitochondria running smoothly. SIRT1 helps insure that communication signals get through between the nucleus and mitochondria. When NAD levels drop, as they do with aging, SIRT1 activity falls off, which in turn makes the crucial signals fade, leading to mitochondrial dysfunction and all the ill effects that go with it.

NAD boosters that can be found on the market might work synergistically with supplements like resveratrol to help reinvigorate mitochondria and ward off diseases of aging. While resveratrol has hogged the anti-aging spotlight over the past decade, an increasing number of studies show that a resveratrol-like substance called pterostilbene, found in grapes and blueberries, is a kind of extra-potent version of resveratrol. The pterostilbene molecule is nearly identical to resveratrol's except for a couple of differences that make it more "bioavailable" (animal studies indicate that about four times as much ingested pterostilbene gets into the bloodstream as resveratrol). Test-tube and rodent studies also suggest that pterostilbene is more potent than resveratrol when it comes to improving brain function, warding off various kinds of cancer and preventing heart disease.

Scientists reportedly have characterized the effects of these precursors to NAD and supplements on metabolism as "nothing short of astonishing," at least in mice. Evidence for the beneficial effects on human cerebral function is just beginning to emerge. Pterostilbene use points to improved brain health as well as we age, with beneficial antioxidant and anti-inflammatory outcomes. Human studies are still lacking, but it may be worth giving these supplements a try to measure any personal improvements to energy or strength, and just cross your fingers that you may be aging more slowly and delaying degenerative disease.

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