People have for centuries been searching for a fountain of youth — or at least to delay the aging process — and science is now finding that mutations in mitochondria may be to blame for our growing older. How can it be that the very thing present in every cell in our body that supports life is also responsible for its degradation? Read on.
Researchers studying animals have known for a long time that mitochondria mutations somehow escalate external aging processes, but they didn’t know exactly how until research out of the Karolinska Institute (KI) in Sweden in recent years caught their attention. In simplistic terms, KI researchers genetically engineered some mice with mutations in an enzyme that helps mitochondria replicate and repair DNA.
Mice usually live about 100 weeks, but within just 25 weeks, the young mice began developing signs of aging, including baldness, reduced fertility, osteoporosis, and heart problems; and they had almost five times more errors in their mitochondrial DNA. Not one of the mice lived past 60 weeks.
This got researchers in the field very excited, including at the University of Washington in Seattle, who suggested it was the first “evidence that mitochondrial mutations cause aging,” and thought it could help engineer mitochondria with enhanced abilities for mitochondria to repair cells and keep them healthier to help slow the aging process for a longer life.
Stick with us. It’s complicated but profound, because the good news for those wanting to live longer, healthier lives that came from the KI study, was that prematurely aging mice can be researched further “to find genetic, pharmacological, and dietary interventions” to help “counteract” growing old.
So does this mean we’re closer to finding a fount-of-youth pill, serum, or supplement?
The good news for those wanting to live longer, healthier lives that came from the KI study was that prematurely aging mice can be researched further to find genetic, pharmacological, and dietary interventions.
To better understand the science and what it means for anti-aging, we turned to the world’s leading expert on cell metabolism, Dr. Charles Brenner — the Roy J. Carver chair and head of biochemistry at the University of Iowa, and founding co-director of the University of Iowa Obesity Initiative, who has discovered genes and enzymes, and a vitamin integral to the life support of healthy cells.
Brenner says that mitochondria functions are so directly connected to aging because they depend on oxygen. “When mitochondria work efficiently, our cells and tissues function beautifully,” Brenner explains. “However, damaged and mutated mitochondria lose efficiency at producing ATP and generate a lot of oxygen free radicals.” ATP is adenosine triphosphate, the biochemical way cells store and use energy, and free radicals are a result of oxygen molecules splitting into unpaired electron molecules and scavenging around in the body to find an electron with which to pair.
Oxygen free radicals can damage DNA, protein, lipids (fatty acids), and tissues. “When our body’s molecules and tissues are damaged,” Brenner says, “we expend energy in repair processes rather than just being fabulous.” And that’s when there’s some slack in the system. “Because even though there are thousands of copies of mitochondrial DNA in every cell, when mitochondrial mutations accumulate to a critical degree or when they are inherited — from the mother — there tends to be a lack of control of oxygen free radicals as well as depressed energy production.” Brenner adds that one of the most common mitochondrial diseases can actually be diagnosed, in part, by droopy eyelids.
He says mitochondria mutations and free radicals out of control are not solely responsible for aging, “because aging is not one thing” — but depressed mitochondrial activity is clearly associated with aging, thanks to the research establishing that mice with sloppy mitochondrial DNA replication accelerate aging.
So can anything be done to prevent our mitochondria from mutating and even reverse the process? The answer may be yes, in part thanks to a vitamin Brenner discovered could help.
Mitochondria are an important part of health and aging, but what we are really talking about is optimizing whole-body metabolism, resiliency, and boosting the body’s repair capacity.
“We get rid of damaged mitochondria with a process called mitophagy. Both exercise and the vitamin I discovered, called nicotinamide riboside (NR), promote mitophagy in model organisms [nonhuman species used by laboratories to help scientists understand biological processes]. Obviously, we know exercise is good for all of us. Now NR is out of the lab and has been shown to be a safe, orally available supplement.”
Brenner explains that NR basically works by boosting NAD, the central catalyst of metabolism. “The connection to mitochondria is that everything that mitochondria do depends on NAD,” noting that it’s not one syllable but three, “almost like DNA in a different order.”
There’s an important aspect of mitochondria specific to mitochondria that is leading to even more research. Brenner explains that moms are the only ones who pass them on. “This is how we trace everyone’s maternal bloodline,” Brenner explains. “The female reproductive system evolved to protect the mitochondrial DNA that goes into eggs, but the mitochondria in the rest of a woman’s organs — including brain and skeletal muscle — have the same potential for decline as the mitochondria in aging men.”
He says this is why menopause is an active area of research, “because mitochondria are required for synthesis of estrogen and there are indications that estrogen can help maintain mitochondrial functions.”
Brenner doesn’t like to think of mitochondria in terms of trying to find a magic pill or elixir. “Mitochondria are an important part of health and aging, but what we are really talking about is optimizing whole-body metabolism, resiliency, and boosting the body’s repair capacity,” he says. “My group discovered the vitamin activity of NR in 2004, and we showed in 2007 that we could extend lifespan in yeast by boosting NAD and the activity of a protein called SIR2.
“But I am the same person who bristles at headlines that call NR (commercially available from ChromaDex as Tru Niagen) an anti-aging or miracle pill. To me, those characterizations are toxic because they put NR into a category with overhyped and ineffective molecules.”
He goes on to explain that multiple conditions of metabolic stress, including overindulgence of food, alcohol, intense noise, and sun damage distress the NAD system in our organs. “In preclinical experiments, we and others have shown that NR helps ameliorate conditions of metabolic stress by rebuilding stores of NAD. Strengthening mitochondrial functions and helping dispose of damaged mitochondria is clearly a component of what NR does.
“While we don’t get out ahead of our skis,” Brenner says, “and you won’t hear people associated with Tru Niagen say that NR is a miracle, it’s an amazing science-based molecule we can safely take to boost and maintain our NAD to help defend ourselves against the inevitable stresses of life and to age better.”
Keeping Your Mitochondria Healthy
Mitochondrial health supplements can help, and there are a number on the market. Brenner says that based on what is known from preclinical studies, NR (the vitamin he discovered) may support mitochondrial function in unique and potentially complementary ways.
“It boosts levels of NAD, supporting the same cellular energy production pathway as supplements such as CoQ10. Cells can also convert NAD to NADP, which functions in the same antioxidant pathway as glutathione. Finally, NAD acts as a cellular signal, activating pathways that help overall mitochondrial efficiency for improved energy production. There is some clinical research in progress on NR that aims to improve mitochondrial function. So far, we know that NR is safe and orally available in humans,” Brenner says.
Maintaining healthy mitochondria also rolls into the general wellness guidelines:
1. Be physically active and mentally and socially engaged.
2. Don’t eat or drink to excess and minimize sweets. A varied diet of minimally processed food is best.
3. Don’t eat too late in the day in order to maintain a hunger cycle.
4. Get good sleep.