Thanks to modern public health practices and medicine, humans are now living longer than ever before. Forecasts show that by 2050, the population over the age of 65 will double. To a large extent, more life has great benefits for society, but also a larger percentage of the population suffers from prominent signs of aging; Including muscle weakness, impaired memory and slow metabolism.
Among the many options for combating aging, a substance called urolithin-A has piqued the curiosity of a number of researchers. For more than a decade, scientists at the Amazentis Society for Life Sciences and the Swiss Federal Institute of Technology in Lausanne have been studying the compound, and Amazonis is currently developing a supplement containing the substance. In some people, urolithin-A is produced naturally by intestinal microbes during digestion of a precursor compound found in pomegranate, berry, and walnut. Orolithin-A is associated with mitochondrial health.
در یک article Which in 2016 in the journal Nature Medicine Researchers have shown that urolithin-A significantly increases the lifespan of worms and has little effect on muscle strengthening, as well as significantly increases the resilience of mice. Over the past five years, they have worked to understand the potential benefits of this compound for humans, focusing on mitochondrial and muscle health. These scientists in 2019 Report The first phase of clinical trials in the journal Nature Metabolism Olitin-A has been shown to be safe for human consumption. They have recently begun experiments to find a link between mitochondrial health and muscle strengthening.
Free radicals and oxidative stress
The most well-known theory of biological aging dates back to the 1950s. Danham Harman, a biochemist at the University of California, Berkeley, suggested that cells metabolize nutrients and consume oxygen. They produce compounds called reactive oxygen species as by-products. Harman’s hypothesis was that these compounds, which chemists call free radicals, react with cellular compounds and cause damage that leads to aging over time. He developed the theory in the 1970s and suggested that mitochondria are the source of free radicals.
With the adoption of Harman’s free radical theory for aging, research was conducted on Alzheimer’s, cancer, and many other diseases. This theory even entered the public mind, and recommendations for eating foods such as blueberries, green tea, and pomegranate, which are rich in natural antioxidants, became popular.
But free radicals alone have not been able to explain all the effects of aging. For example, although naked rats live longer than other rodents, they also have very high levels of oxidative stress. So researchers moved on to other theories.
Mitochondrial diarrhea and inflammatory aging
Biologists quickly discovered a link between mitochondria and aging – a link that comes from the strange roots of mitochondria. It is believed that about 1.4 billion years ago, somewhere in the Earth’s early oceans, a eukaryotic cell swallowed an oxygen-producing bacterium, and after several generations, a mitochondria formed. Although mitochondria are organs that are fully integrated into the body of organisms, they have never lost their ancient genome (now known as mitochondrial DNA) (mtDNA).
As mitochondria age, their shape changes and their activity decreases. They eventually die and release mtDNA. Because the origin of mitochondria is an external organism, researchers speculate that the release of mtDNA triggers an immune response. Several studies show that this leads to persistent inflammation in living organisms – a phenomenon called inflammatory aging, which can play a role in many aging-related diseases.
The mtDNA itself changes with age. As a person gets older, his or her mitochondrial genome accumulates mutations and deletions faster than cell nucleus genes. These mutations have been linked to signs of aging. For example, mice that have a defective DNA replication enzyme called mtDNA polymerase have more mitochondrial DNA mutations than a normal mouse. They also develop osteoporosis and gray hairs and die at a young age.
However, Toren Finkel, director of the Institute for Aging at the University of Pittsburgh Medical Center, says the links could be linked to aging, not to it. “Mitochondrial dysfunction is probably the result of other problems in the mitochondria, not necessarily their DNA.”
Healthy mitophages and mitochondria
A few years ago, Johan Auwerx, a physician, biologist, and professor at the Swiss Federal Institute of Technology (EPFL), and Amazantis researchers addressed the question of whether unhealthy mitochondria lead to muscle weakness; One of the signs of aging. They compared mitochondrial function in two groups of people over 60 – healthy and active and weak, whose muscle function was already depleted. Using weakly radioactive trackers to measure the extent to which participants’ muscle mitochondria use ATP, the researchers found that weaker individuals had less muscle metochondrial activity.
The researchers argued that if lazy mitochondria stimulate aging, then perhaps the production of fresh, healthy mitochondria could trigger tissue rejuvenation. In fact, when mice produce new mitochondria, some of the effects of aging appear to diminish; However, how this process works is still not well understood.
Cells also play with defective mitochondria. To study this process, called mitophagy, Finkel’s team genetically engineered mice to produce a fluorescent protein in their mitochondria. They then dissected various animal tissues and cells that regenerated fluorescent mitochondria. “Young animals have very high mitophage rates in their brains, and older animals have much lower mitophage rates,” says Finkel.
Towards rejuvenated mitochondria
These results suggest that mitophage amplification can produce an overall healthier mitochondrial population, possibly reversing the clockwise direction in tissues. To test this hypothesis, Aurex and Amazantis researchers have focused their studies on urolithin-A.
In the 2016 article Nature Medicine The team fed the aging C. elegans tube worms urolithin-A. This combination activated their mitophagia, increased the lifespan of the worms by 50%, and there was ample evidence that mitophagia is essential for prolonging life. When the researchers tested the same compound on mice, their resilience (when running in a roll) increased by 57% compared to sedatives.
Since then, researchers have conducted several clinical trials to evaluate the effect of urolithin-A supplements on humans. In the first phase of the clinical trial reported in 2019 Nature Metabolism Released, they showed that urolithin-A is safe for human consumption and increases the presence of mitochondrial genes in muscle.
An accurate and tested dose of urolithin-A is needed, according to Anurag Singh, head of Amazonas Medical. Metabolism is formed by the gut microbiota when precursor compounds called ellagitannins – found in foods such as pomegranates, berries and walnuts – are consumed.
But the variety of gastric microbiota varies from person to person. the door A clinical trial Recently published in the European Journal of Clinical Nutrition, Arx and the Amazon team surveyed 100 people and reported that about 40% of them could naturally produce significant levels of urolithin-A through diet alone. . The experiment also showed that an Amazon supplement could produce the equivalent of six glasses of urolithin-A pomegranate juice. At the same time, a clinical trial has been conducted to see if urolithin-A improves muscle health and strength, but the results have not yet been published.
Improving mitophagia can also improve muscle function in young people, according to research by Louise Burke and John Hawley, researchers in sports nutrition at the Mary McClump Health Research Institute at the Catholic University of Australia. In collaboration with Amazonis, they are measuring the effect of urolithin-A on the resilience of professional athletes and performing muscle biopsies to measure mitochondrial changes. “At many sporting events,” says Brooke, “athletes compete in several races to win gold medals,” and improving mitophagia can help them recover faster after each race and compete at full strength for several days. .
Howley warns that nutrition, including supplements, “will not replace your workout or lifestyle.” Because exercise improves muscle function by stimulating the production of new mitochondria. However, maintaining a stable number of healthy mitochondria can help people suppress the effects of aging for longer.