Once a powerful Sumerian king named Gilgamesh set out on an intrigue, as the characters of myths and legends often do. Gilgamesh witnessed the death of his best friend Enkidu and, fearing a similar fate, set out in search of immortality. The great king could not find the secret of eternal life, but he did not grieve too much, since his exploits will live much longer than his mortal years.
Fast forward four thousand years, plus or minus a century, and Gilgamesh, still known to this day, despite the past time, would be glad to know that today many are engaged in the search for longevity. But instead of fighting epic monsters and cunning gods, people are engaged in science and business in order to extend their lives and uncover the secrets of human biology.
Among them is Aubrey de Gray, a biomedical gerontologist and founder of the SENS Research Foundation, which is looking for ways to improve regenerative medicine and apply it to age-related diseases. SENS stands for Strategies for Engineered Negligible Senescence. With this term, de Gray describes a wide array (of seven, to be precise, points) of medical interventions that can heal or prevent various types of molecular and cellular damage that ultimately lead to age-related diseases like cancer and Alzheimer's.
Many of these strategies focus on senescent (senescent) cells that accumulate in tissues and organs as people age. Not completely dead, aging cells stop dividing but remain metabolically active, spewing out all kinds of proteins and other molecules that can cause inflammation and other problems. For a young body, this is not a problem (and probably partial maintenance of overall biological functionality) as a healthy immune system can handle it.
But as we age, senescent cells continue to accumulate, and at a certain point, the immune system ceases to cope with them. Welcome to old age.
About mice and people
Researchers like de Gray believe that treating the cellular basis of aging can not only prevent disease, but also significantly increase a person's lifespan. How much? According to de Gray, in biblical proportions - forever.
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De Gray says science has taken a big step forward in the past 15 years. For example, scientists have learned to copy mitochondrial DNA into the nucleus. Mitochondria serve as power plants for the cell, but are extremely vulnerable to mutations that lead to cellular degeneration. Copying mitochondrial DNA into the nucleus will help protect it from damage.
Another achievement that was achieved six years ago was that scientists first figured out how to kill senescent cells. This discovery led to new experiments in mice that showed that removing these cells - ticking bombs - prevented the development of disease and even lengthened the lifespan of rodents. Now, this anti-aging therapy is about to be tested in humans.
“I think there will be a stream of advances in the next few years - once the first steps are taken, development will be progressively easier and faster,” says de Gray. “I think the chances are high that we will achieve radical rejuvenation of mice in six to eight years. Perhaps we can take middle-aged mice and double their lifespan, which is an order of magnitude more than can be done today."
Around and around
Richard Farager, professor of biogerontology at the University of Brighton in the United Kingdom, recently made a laboratory discovery related to the rejuvenation of senescent cells through chemical compounds found in chocolate and red wine. He hopes to apply his findings to animals in the future - in this case, horses.
“We are fortunate enough to have received funding from a charity to consider possible treatments for old horses,” he says. “I think this is a great idea. Many aspects of physiology that we study are similar in humans and horses.”
Last year, Farager and colleagues demonstrated in a paper published in BMC Cell Biology that resveratrol-based chemicals were able to reactivate a protein, a splicing factor involved in gene regulation. The chemicals made the cells rejuvenate and divide like young ones.
“If the treatment worked in the old pony's systems, I’m confident it can be transferred to human clinical trials,” Farager says. “Time is an exclusively monetary question. With normal funding, clinical trials could be completed in five years.”
Time is money, money is time
Farager argues that the latest breakthroughs are not related to new technologies like artificial intelligence or the CRISPR gene editing method, but to a paradigm shift in understanding cellular aging. Solving the “aging problem” is not a matter of technology, but of money.
“Honestly, when AI and CRISPR remove cystic fibrosis, Duchenne muscular dystrophy, or Gaucher syndrome, I'm much more eager to hear stories of amazing progress. Fix one common genetic disease in the population with these cool stuff, and then let's talk. I believe in the most powerful technological development of all: money."
De Gray is more serious about the role technology will play in the fight against aging. AI, CRISPR, protein engineering, advances in stem cell therapy, and immune system engineering will all contribute.
“There is really nothing special about how these technologies will contribute,” he says. "The peculiarity is that we need all of these technologies, because there are many different types of damage to repair, each of which requires a different approach."
It's about blood
The San Francisco-based startup believes machines will play a big role in finding the right combination of factors that will lead to a long, healthy life - and then in developing drugs that take advantage of these discoveries.
BioAge Labs raised about $ 11 million last year to develop its machine learning platform, which scans large datasets in search of blood factors, such as proteins or metabolites, that are associated with biological age. According to startup founders, these factors can predict how long a person will live.
“Our interest is in parabiotic research, where it has been shown that linking the circulatory systems of old and young mice so that they have the same blood for two makes old mice healthier and more alive,” says Eric Morgen of BioAge.
Armed with this idea, one could change the good and bad factors to produce a rejuvenating effect.
“The focus at BioAge is to identify these factors in human data, characterize the important molecular pathways in which they are involved, and then use those pathways,” he says. "It's complex, and we're using machine learning to mine complex datasets and determine which individual factors and molecular pathways best reflect biological age."
Saving for the future
Of course, there is no information on when any of these anti-aging therapies will hit the market. That's why Forever Labs, a biotech startup based in Ann Arbor, Michigan, needs your stem cells now. The company offers services for cryogenic freezing of stem cells taken from bone marrow.
At the heart of the procedure, according to Forever Labs CEO Stephen Klausnitzer, is the theory of research showing that stem cells may be a key component in repairing damaged cells. This is because stem cells can evolve into many other types of cells and divide endlessly to replenish other cells. Klausnitzer notes that thousands of clinical studies are looking at the use of stem cells to treat age-related diseases.
However, stem cells have their own expiration date, which usually coincides with the age at which most people begin to experience serious health problems. Stem cells harvested from bone marrow at an earlier age have the potential to provide a resource for future treatment.
“We firmly believe that with access to your innermost reserves, you can live a long and healthy life,” he says. "There is good reason to believe that if you start to maintain the bone marrow population, the number of cell nuclei in the bone marrow, and replenish it so that it does not decline with age, you can absolutely avoid cardiovascular disease, stroke and Alzheimer's."
Stored stem cells can also be used today to develop treatments for chronic diseases like osteoarthritis. But the most exciting prospect - and the reason he himself put his 38-year-old stem cells on ice - lie in therapies of the future that will use stem cells.
“I can start injecting them back not to treat age-related diseases, but to reduce stem cell decline so that I never get sick at all,” he says. "I don't think it can be compared to immortality, but definitely a step in that direction."
Careful with immortality
The social implications of the longer-lived human species are fortune telling. We know that by the middle of the century the world's population aged 65 and over will reach 1.6 billion; at the age of 80 - almost 450 million. If many of these people can live healthy lives in their old years, colossal medical and healthcare costs can be avoided.
Farager is working on a future in which human health is most important. Human immortality is a completely different matter.
“The longer life expectancy, the more we will need birth control and the less new minds we will have. For progress, this can go sideways."
And who really wants to live forever?
“There were happy moments in my life, but there were also strong disappointments. No drug will wash these feelings out of me,”says Farager. “I no longer look to the future with boundless enthusiasm and I don’t think this is a midlife crisis. No wonder there are so many "immortalists" - young people. They need to be careful with their desires."
Ilya Khel