AT St Jude for Children in Memphis, Tennessee, an extraordinary clinical trial, if it succeeds, can have wider repercussions in the field of chronic diseases associated with age. At first glance, it may seem that the survivors of childhood cancer may seem like an unusual society in which aging is taught, but as Greg Armstrong, the main investigator of St. Jude’s study of childhood cancer, we now know that they represent a group of individuals who are progressing in aging at an unusual speed quickly quickly Unusual.
Because modern chemical treatments and radiotherapy have become Increasingly In the treatment of childhood cancers, this comes at a great cost, due to the erosion of such treatment on the bodies of these children, which becomes more clear when they reach middle age.
“Among these children, 85 % will overcome their cancer, but it won a cost,” says Armstrong. “We know that these children will shorten their age. They often die of chronic diseases such as heart disease, stroke, or highly advanced secondary cancer. We have discovered a decade ago that this increases the age faster than their time.”
In particular, this is reflected not only in biology, but in material weakness. When Kirsten Nice, a physiotherapist and clinical epidemics specialist in St. Jude, Evaluating a group of child cancer survivors They are between 24 and 41 years old, I noticed that when it comes to the function of the heart, flexibility, respiratory ability and extent of movement, it is similar to that of people who are decades. “We have shown that at the age of thirty, they have a physiological fragility that resembles people in the 1970s and eighties of the last century, and the matter gets worse over time.”
The reason behind this is aging, a condition in which the cells stop continuing to divide as normal, but instead remains, they refuse to die. Because of this quality, aging cells are sometimes described as “coma cells” and are now considered a driving force and a reflection of aging. Over the course of life, our bodies incur increased amounts of damage that in turn makes many cells, distributed throughout the body, are more likely to become aging.
For survivors of childhood cancer, He appears The result of undergoing the treatment of such radical treatments at an early age leaves them with a large number of major cells, which usually take decades until they accumulate. Nice explains that this drives the loss of function and the risk of disease, not only because the annual cells stop working as they usually do. Aging cells also generate a stream of inflammatory molecules, which is something known as the name The apparent pattern of dislocating the secretion associated with aging (SASP). “If we look at data from our childhood cancer survivors, we can see that they have this low -grade inflammation,” says Nice. “Thus they do not feel satisfied, they do not move wonderfully.”
Over the past decade, attention has grown steadily in a category of medicines known as seenolytics, called this because they have proven that they are able to get rid of aging cells in mice by disrupting certain paths, causing them to self -destruction. One of the most well studied Senolytics is actually a chemotherapy drug called Dasatinib, while others include natural quercetin and Vistine, which are found in various fruits and vegetables.
Now, Armstrong leads trial Of the 50-60 survivors of childhood cancer with signs of weakness, along with blood-dependent signs indicating a large amount of aging. On average, the participants are about 40 years old, on average, oral doses either from Dasatinib and Quecetin, or FISETIN, to see if it can improve their physical function for six months. These individuals will then follow every five years to evaluate whether this treatment can help prolong the average life expectancy.
For old age researchers around the world, this data is a first initial step towards indicating whether Senolytics can one day be used as a way to extend a healthy age of all older adults.
AJohannes Grillie, director of the Ludwig Boltsman Institute for shocking in Vienna, discussed the future of Centuryic in front of an audience of old age scientists in Vienna, the British Research Association discussed at the September Aitgest Aitgest Conference in Senlitic in front of an audience of aging scientists.
As Grillaryi explained, while scientists continue to evaluate the long -term safety file for these drugs, they will be mostly used in the experiences of patients with advanced diseases, where the accumulation of annual cells is believed to be a major contribution.
Grilli later told observer. “But the promise is that these cells seem common denominator in every age -related disease that has been seen at all: cardiovascular diseases, neurological degenerative diseases, muscle muscle diseases, lung fibrosis, and chronic kidney disease, called it whatever you want. If we use Senolytics, then we are We see that the inflammation disappears and the renewable ability of the surrounding tissues is restored – at least if you are a mouse.
Based on dozens of pre -clinical studies in which rodents were treated to develop various chronic diseases before treating them, Senolytic has now begun to reach humans. Data so far is limited but clinical experience In patients In the early stages of Alzheimer’s disease, while this same mix was proven previously Reducing some physical defect In people with chronic lung disease.
Grillaryi-co-founder also hopes for Rockfish Bio, its Senolytic company-in launching experiments in other diseases, in addition to the company’s Senolytic for the company to try to renew devices from the most older donors. While NHS says there is no limit to organizing organs, I have already showed the research The beneficiaries of the members who donated more than 60s tend to obtain bad results because the member is likely to have damage, while the rejection rate is much higher.
“There was a study on the 2000s that showed that the more your advanced cells increased in a human transplant, the greater the results of the transplant,” says Grillaryi. “Since the annual cells are pro -inflammatory, they attack the immune system of the recipient, and it seems that it attacks the donor frequently. Hope is to help seenolytics, because kidney transplant members, for example, are very rare.”
All of this will provide more data on the safety and effectiveness of various curiches, while many studies continue to focus on its potential interest in young people with advanced disease. Dutch government agencies are funded trial Where Dasatinib and Quercetin will be provided to patients between the ages of 18 and 65 with a diagnosis of non -alcoholic fatty liver, or chronic disease associated with follow -up, where the annual cells are believed to lead fibrosis, or scarring, throughout the member, which weakens its ability to work. According to Stijn Meijnikman, a gastroenterologist and liver disease, the experiment leads, hope is that removing these cells will enable the liver to repair itself.
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“In mice, you see that if you get rid of the annual cells, you get rid of fibrosis,” says Meijnikman. “So we look forward to seeing indications of this in humans. It is a very short trial, but we hope that the disruption of paths that allow aging cells briefly will be briefly to enable them to clean them by the immune system.”
The broader community of age scientists and investors is still fascinated by whether these medications can eventually help in contrast to some signs of aging in the middle of life at a later time, and perhaps until the age of man extends.
“More people are aware of the concept of annual cells and how you can positively influence it,” says Mark Bernigger, the founder of LongVity Investors, a financing network.
ZIn a picture that Grillalari pulled into contact with our teams, it is easy to understand excitement. It shows an elderly mouse of 34 months – equivalent to 90 in human years – thinning of fur and gray. “Like us, they get bald spots as they get older,” Grillaryi laughs.
In another image, after you deal with Senolytic, the mouse itself appears clearly younger. The fur has grown again and regained its original pigmentation. If such a medicine achieves similar results in humans, it will undoubtedly be great.
But many of them urge caution. Professor Tohro Menamino of Juntendo University in Japan, who studied cellular aging for two decades, indicates that some annual cells are useful for our body, as they play important roles in the main physiological functions such as wound healing. Simply cleansing everything can have long -term negative consequences.
Minamino believes he may have the answer. In 2021, he and his colleagues “Aging vaccine” revealed A protein called GPNMB is used to selectively remove annual cells that contribute to inflammation. “We are trying to target the bad guys specifically,” he says.
Again, this has been proven that this works well in mice, as old rodents show functional declines after receiving the vaccine and living for a longer period. MINAMINO now hopes to develop this as a RNA vaccine, similar to the Jab Covid, which trains the immune system to remove inflammatory aging cells and can be used in patients with Alzheimer’s disease, chronic lung disease or weakness.
“One of the challenges at the present time is that we do not have good tools in particular to estimate the number of annual cells in the human body and the extent to which this changes with treatment,” says Minamino. “But if we are able to develop better imaging systems to measure how these cells accumulate, you can imagine a future as this can be part of an annual medical examination.”
In the end, researchers warn that aging cells are still only one piece of aging puzzle. Meijnikman also indicates when I ask whether Senolytics can be used to revive the liver of children between the ages of 80 years, which has been exposed to severe drinking contracts or a bad diet, this is not only related to disinfection of aging.
“Your body still needs the ability to renew,” he says. “There is still an open question about what will happen if we get rid of the annual cells, but there is no new cell reservoir to replace them anymore because your stem cells are no longer working. We will move this way in the future, and we deal with more and more elderly, but we are at the present time, We first need to collect more evidence that Senolytics can really work in humans.