We live longer than we should. DNA research shows that the modern man is actually made to live to be about 38 years old, but the average life expectancy worldwide has now reached 71 years.
This uplifting figure has its downside, however, because with increasing age, the risk of aging-related diseases such as osteoarthritis, diabetes and Alzheimer’s increases considerably.
Aging is an incurable disease
In the United States, almost half of people aged 45-64 suffer from one or more chronic diseases, and the same story can be said about 80% of people who are 65 years or older.
Aging is arguably the biggest risk factor for all incurable diseases. Therefore, a group of scientists now wants to treat aging in the same way as incurable diseases.
The scientists believe that by slowing down the aging of the cells with drugs, it is also possible to prevent a variety of other diseases that usually accompany increasing age.
your life
They have launched a project called TAME (Targetin Aging with Metformin), but they are not alone in this opinion. In laboratories around the world, people are now working to find ways to extend human life.
It is a novelty in itself that for this purpose not only new drugs are sought, but also the effects of drugs that are already in use among millions around the world are studied.
An ancient dream vision
For millennia, mankind has tried to fight the inevitable aging process. It’s been well over 2,000 years since the king of Macedonia, Alexander the Great, went in search of the River of Paradise, which legends said could give this warlord eternal life.
And in the 16th century, Spanish explorer Juan Ponce de León traveled to Florida to find the fountain of youth he had heard stories about.
In the 19th and 20th centuries, scientists tried to slow aging with everything from blood transfusions to testicular transplants. Now scientists are going a little differently.
The TAME project, for example, tests a drug that millions of people are already using.
This project is led by Nir Barzilai, director of the Wave Research Institute of the Albert Einstein College of Medicine in New York, and now the researchers are investigating whether the diabetes drug metformin has a positive effect on the aging of the body.
The experiment aims to show whether the drug prolongs the life of cells in the body and postpones the development of various diseases such as cardiovascular diseases, cancer, diabetes or dementia.
The experiment will last for six years and will involve researchers at 14 research institutes in the USA and more than 3,000 participants aged 65-79.
This study is the first to target anti-aging with drugs, but it also has its critics.
Metformin has been in use for over 60 years and has been approved by the US Food and Drug Administration as a diabetes drug since 1994. Why waste time and money testing an already used drug?
Animal experiments attracted attention
For Nir Barzilai and his colleagues, the answer is no: Metformin has already passed the strict requirements and is considered a safe drug.
It saves the scientists the long time it would take to get a new drug approved and experiments can be started immediately.
A three-pronged attack on the cells
Throughout human life, cells are dying in the body. But fortunately, these microscopic building blocks are able to divide and new cells keep the body healthy. With age, however, the cells gradually stop dividing and also lose energy. A vicious cycle ensues and the cells release harmful substances.
The effect of the drug on animals is already confirmed. In 2010, researchers at Rutgers University in the US discovered that metformin increased the average lifespan of the worm C. elegans.
Worms that received the drug lived an average of 40% longer than worms in a control group.
The substance has been found to have the same effect on mice that lived 38% longer on average when they received metformin daily. However, results from animal experiments cannot always be transferred to humans, and the importance of the TAME project lies in obtaining a conclusive result on whether the drug works against aging in humans.
In 2014, a team of researchers at Cardiff University in Wales studied the medical records of 78,241 patients with type 2 diabetes. These patients had all been taking metformin for seven years.
The researchers compared the health of these patients with 90,463 healthy individuals, and to their great surprise, it was found that the diabetic patients lived 15% longer than the healthy ones.
The discovery is surprising because type 2 diabetes is accompanied by a considerable weakening of general health and is accompanied by a greatly increased risk of cardiovascular, kidney or neurological diseases, in addition to the increased risk of vision.
Metformin attacks aging from various aspects. The substance improves the function of the energy granules, which are a kind of energy store of the cells and convert energy in carbohydrates and fats into ATP, energy that the cells can use.
This releases so-called free radicals that damage the energy particles and accelerate aging. Metformin, on the other hand, increases the activity of the energy granules and also reduces the release of free radicals.
The substance additionally activates certain enzymes that are also active when fasting or when nutritional intake is very low.
One of these enzymes, AMPK, acts as a kind of sensor that measures the energy status of the cell and is usually activated when the amount of ATP is at a minimum. Experiments with the worm C. elegans have shown that the animal lives longer when this gene is highly active.
The AMPK enzyme slows down aging by inhibiting a protein structure called mTOR, which is made up of many proteins. Studies, including worms, banana flies and mice, show that the animals live almost twice as long if restrictions are placed on the mTOR proteins or they are removed.
The AMPK enzyme is not the only side product of metformin. The medicine also works against excessive cholesterol, which, among other things, increases the risk of blood clots.
Likewise, the drug reduces chronic inflammation, which becomes more frequent with age and increases the likelihood of cardiovascular disease, arthritis and cancer.
At 122 years and 164 days, the oldest person to date was the French Jeanne Calment, who died in 1997.
Atrophied cells spread aging
Biological aging is broad and includes many changes in the body. That is why there is also a multitude of possible methods to use drugs against it.
One method is based on attacking atrophied cells that are still alive. When a cell is no longer able to divide or is seriously damaged, it destroys itself and dies. At the same time, they make room so that new cells can be formed instead.
Occasionally, however, cells are damaged in such a way that they lose this ability to die. Such cells release harmful substances into the body and are involved in triggering age-related diseases.
Usually, the immune system is responsible for defeating these diseased cells, but the immune system also shows signs of aging, so such cells accumulate in proportion to age, and this can have a very harmful effect on health.
In 2018, researchers at the Mayo Clinic in the US transplanted about a million such senescent cells into the fat tissue of mice.
These mice chased much faster than mice in a control group that only received transplanted adipose tissue.
Subsequent experiments showed that half a million apoptotic cells were enough to accelerate fatal diseases such as cancer and lung disease in mice.
However, the scientists found an effective method to eliminate these harmful cells.
Shortly after transplanting the deficient cells, half of the mice were treated with the substances dasatinib and quercetin.
Within three days, the number of affluent cells was greatly reduced, and these mice completely escaped the attacks that plagued the untreated mice.
The treatment also worked when the drugs were not given until five weeks after the deflagrated cells were placed in them and their health began to decline.
Just two weeks after the treatment, these mice were running around again, and their mortality within a year was 36% lower than that of untreated mice.
19,093,000 will be over 100 years old in 2100 according to the UN forecast.
These positive results led the researchers at the Mayoklinikin to begin experiments with the same type of medication on people with diabetic kidney disease, a disease characterized by a large amount of abnormal cells.
Nine participants in the trial were given dasatinib and quercetin for three days. Both before the last dose and 11 days later, blood, skin and blood samples were taken.
The samples revealed that the number of deflagrated cells had decreased and at the same time there were less harmful substances in all sample types after the treatment.
There are other agents that remove depolarized cells in the same way as dasatinib and quercetin, and new agents with these properties are being added all the time.
Many researchers express their satisfaction with the possibilities that these substances seem to offer, not least because side effects are very rare and the substances can have a great effect immediately after relatively small doses.
Also, unlike many other medications, these medications do not need to be continued. Once the malignant cells have been eliminated, the goal is achieved.
Direct effects on aging and aging-related diseases have not yet been studied in sufficiently large groups. However, the results of a so-called preliminary study published in the journal Lancet in 2019 show a positive effect.
A total of 14 patients with the disease IPF (Idiopathic Pulmonary Fibrosis) were given medicine in injection form twice a day. IPF is a rare lung disease that breaks down healthy lung tissue and replaces it with scar tissue.
The initial study showed that the number of abnormal cells that cause the disease was reduced by more than 30%.
Enzymes heal cells
Other substances that could potentially be available to doctors of the future, repair the cells and heal them.
With age, the power plants of the cells, the energy granules, gradually lose their ability to produce ATP, the chemical energy of the cells.
Top 5 Oldest Animals
1. Shellfish
Cow shell: At least 400 years old.
2. High speed
Shark: At least 122 years old
3: Mammals
Plainback: 211 years old
4. Bony fish
Goldfish: 204 years old.
5. Reptiles
Ray turtle: 188 years old.
This is caused, among other things, by the fact that the amount of NAD+ molecules decreases, but these molecules play a key role in the formation of ATP. In addition to maintaining ATP production, NAD+ plays the role of activating the cell’s repair process and thus plays a role in delaying aging and slowing down age-related diseases such as diabetes 2, heart disease, Alzheimer’s and cancer.
Namely, the substance has a decisive significance for the activity of various enzymes that protect the genome from attacks by abnormal cells and repair possible damage to genetic material.
Without NAD+, these enzymes do not work, so scientists are looking for ways to increase NAD+ levels.
In this regard, people are pinning their hopes on various molecules closely related to NAD+ called NAD+ amplifiers.
The most studied types are called NMN and NR. Experiments have revealed the beneficial effects of NMN on age-related diseases, such as cardiovascular disease, type 2 diabetes and Alzheimer’s. NR has also been shown to maintain stem cells and extend the lifespan of mice.
A trial of healthy men and women aged 55-79 showed that taking 500 mg of NR twice a day for six weeks increased NAD+ levels by 60% and reduced the risk of heart attack by 25%.
It is still unproven whether older people can use the NAD+ boosters without risk. Previous experiments on mice showed, among other things, that increasing the amount of the molecules could increase inflammation in the body.
However, these side effects of amplifiers do not give any unequivocal reasons for pessimism, and scientists are now working to develop a combination of amplifiers and drugs that have no side effects at all.
Gene therapy extends life
In 2016, Danish researchers implanted a functional gene into experimental mice. The gene codes for the enzyme telomerase, which extends the life of so-called telomeres, which are cut off from the ends of chromosomes during cell division.
Telomeres protect the chromosomes and the longer they can be preserved, the more aging is slowed down. The mice injected with the gene chased more slowly and lived an average of 30% longer.
Antidiabetic drugs slow down old cells
The drug metformin slows down the aging of the body by activating a special enzyme that reduces the production of harmful substances.
Whether gene transplantation has these same effects on humans is still uncertain, and everyone has their own opinion about this method. In 2015, Elizabeth Parrish, CEO of the American biotechnology company BioViva, had the gene injected into herself.
The following year, she declared that the gene transplant had extended the lifespan of the cells by 20 years.
This was done in Colombia in South America and thus outside the territory of the US health authorities. This will likely not be the last time Colombia undertakes to host controversial rejuvenation procedures.
The American biotech company Libella Gene Therapeutics plans experiments with the same type of gene transplant right there. But eternal youth does not come cheap. Those who want to participate in the experiment have to pay the company another million dollars out of their own pockets.
