Reversal of Aging is Closer

The cure for aging has long been the Holy Grail of medicine. Emerging technologies, like the gene editing tool CRISPR, have opened the floodgates to what may be possible for the future of medical science. The key to slowing down aging, however, may lie in a simple and age-old technique. For the first time, Israeli scientists showed the reversal of aging in two key biological clocks in humans, by giving patients oxygen therapy in a pressurized chamber. The results appear in the journal Aging.

As you grow older and your cells continue to divide, sequences of DNA at the end of chromosomes, called telomeres, gradually become shorter. Once the telomeres become too short, the cell can no longer replicate and eventually dies. This isn’t necessarily a bad thing.

Telomere shortening can prevent rogue cancerous cells from multiplying uncontrollably, but unfortunately, this comes with the cost of genetic aging. These geriatric cells that can no longer divide are also known as senescent cells, which accumulate over the period of your life and are believed to be one of the leading causes of aging. In a clinical trial, 35 healthy adults aged 64 and older received 60 oxygen therapy sessions daily over the course of three months. The scientists collected the subjects’ blood samples prior to treatment, after the first and second months of the trial, and two weeks after the trial was over. None of the patients had any lifestyle, diet, or medication changes throughout the study, and yet their blood work showed significant increases in the telomere length of their cells and a decrease in the number of their senescent cells. This isn’t the first time doctors have put patients into pressurized oxygen chambers. Hyperbaric oxygen therapy (HBOT) has been used for almost a century to treat a number of illnesses, including decompression sickness in deep-sea divers and carbon monoxide poisoning.

The therapy involves breathing pure oxygen in a pressurized chamber, which causes blood and tissues in your body to become saturated with oxygen. Strangely enough, this can trigger similar physiological effects that occur when your body is starved of oxygen, known as hypoxia. While previous research shows these effects can stimulate your brain and increase your cognitive abilities, this is the first study to show the therapy may also reverse aging.

Since telomere shortening is considered the ‘Holy Grail’ of the biology of aging, many pharmacological and environmental interventions are being extensively explored in the hopes of enabling telomere elongation,” said study coauthor Shai Efrati, a professor at the Sackler School of Medicine at Tel Aviv University. The significant improvement of telomere length shown during and after these unique HBOT protocols provides the scientific community with a new foundation of understanding that aging can, indeed, be targeted and reversed at the basic cellular-biological level.

This also isn’t the first time scientists have claimed to reverse aging. Several studies using pharmacological drugs, such as danazol, have been shown to elongate telomeres. Additionally, lifestyle changes, including exercise and healthy diets, have been shown to have small effects on the growth of telomeres. “Until now, interventions such as lifestyle modifications and intense exercise were shown to have some inhibition effect on the expected telomere length shortening. However, what is remarkable to note in our study, is that in just three months of HBOT, we were able to achieve such significant telomere elongation—at rates far beyond any of the current available interventions or lifestyle modifications,” study coauthor Amir Hadanny, a neurosurgeon at the Sagol Center of Hyperbaric Medicine and Research in Israel, explained in the press release.

Source: https://www.popularmechanics.com/

How To Protect Cells From Premature Aging

Molecules that accumulate at the tip of chromosomes are known to play a key role in preventing damage to our DNA. Now, researchers at EPFL (Ecole Polytechnique Fédérale de Lausanne in Switzerland) have unraveled how these molecules home in on specific sections of chromosomes—a finding that could help to better understand the processes that regulate cell survival in aging and cancer.

Much like an aglet of a shoelace prevents the end of the lace from fraying, stretches of DNA called telomeres form protective caps at the ends of chromosomes. But as cells divide, telomeres become shorter, making the protective cap less effective. Once telomeres get too short, the cell stops dividing. Telomere shortening and malfunction have been linked to cell aging and age-related diseases, including cancer.

A new study by EPFL researchers shows how RNA species called TERRA muster at the tip of chromosomes, where they help to prevent telomere shortening and premature cell aging

Scientists have known that RNA species called TERRA help to regulate the length and function of telomeres. Discovered in 2007 by postdoc Claus Azzalin in the team of EPFL Professor Joachim Lingner, TERRA belongs to a class of molecules called noncoding RNAs, which are not translated into proteins but function as structural components of chromosomes. TERRA accumulates at chromosome ends, signaling that telomeres should be elongated or repaired.

However, it was unclear how TERRA got to the tip of chromosomes and remained there. “The telomere makes up only a tiny bit of the total chromosomal DNA, so the question is ‘how does this RNA find its home?’”, Lingner says. To address this question, postdoc Marianna Feretzaki and others in the teams of Joachim Lingner at EPFL and Lumir Krejci at Masaryk University set out to analyze the mechanism through which TERRA accumulates at telomeres, as well as the proteins involved in this process. The findings are published in Nature.

By visualizing TERRA molecules under a microscope, the researchers found that a short stretch of the RNA is crucial to bring it to telomeres. Further experiments showed that once TERRA reaches the tip of chromosomes, several proteins regulate its association with telomeres. Among these proteins, one called RAD51 plays a particularly important role, Lingner says.

RAD51 is a well-known enzyme that is involved in the repair of broken DNA molecules. The protein also seems to help TERRA stick to telomeric DNA to form a so-called “RNA-DNA hybrid molecule”. Scientists thought this type of reaction, which leads to the formation of a three-stranded nucleic acid structure, mainly happened during DNA repair. The new study shows that it can also happen at chromosome ends when TERRA binds to telomeres. “This is paradigm-shifting,” Lingner says.

The researchers also found that short telomeres recruit TERRA much more efficiently than long telomeres. Although the mechanism behind this phenomenon is unclear, the researchers hypothesize that when telomeres get too short, either due to DNA damage or because the cell has divided too many times, they recruit TERRA molecules. This recruitment is mediated by RAD51, which also promotes the elongation and repair of telomeres. “TERRA and RAD51 help to prevent accidental loss or shortening of telomeres,” Lingner says. “That’s an important function.”

Source: https://actu.epfl.ch/