Nobuaki Nagashima suffers from a rare syndrome that speeds up the aging process. And hopes to help one day to find a cure.
When the native of the Japanese northern island of Hokkaido Nobuaki Nagashima (Nobuaki Nagashima) was about 25 years old, he began to feel as if his body was falling apart. It was impossible to explain this – he trained for 12 years in the army, honing his skills at any time of the year (it is not specified how he ended up in the army at a young age). However, the body gave up: at the age of 25, he was diagnosed with a cataract (visual impairment with the threat of its complete loss), in 28 hips began to hurt regularly, and by the age of 30 the skin on his legs began to collapse.
Three years later, Nagashim was diagnosed with Werner syndrome , which is characterized by premature aging with a wide range of pathologies. Including diabetes, atherosclerosis, benign and malignant tumors.
There is no cure for illness, so ten years later, by the age of 43, Nagashim, once strong, turned into a decrepit old man. The scientific publication Mosaic tells about how this syndrome works and whether it can help in the future to conquer old age . The material does not provide photographs of victims of the disease.
Old age at 25
For the past 10 years, Nagashima has become a frequent visitor to all the various hospitals. The disease deprived him of the opportunity to continue his military career and forced him to go through five or six operations all over his body. Since he was diagnosed, he has lost 15 kilograms, cannot walk without a cane for more than a few meters and is only able to earn extra money in the city hall when he has the strength.
When he first learned about his illness, he did not hold back tears and did not hide the diagnosis from his parents. Hearing the news, his mother asked for forgiveness that she could not give birth to a healthier person.
Nagashima’s father said that if he can accept and tolerate the disease, then he is a really strong person, and one day, perhaps, he will help scientists gain the knowledge necessary to save other people.
In addition to the X and Y sex chromosomes, a person inherits two copies of each gene in our bodies – from mother and father. Werner syndrome is a so-called autosomal recessive disorder. This means that it appears only when a person inherits the mutated version of the WRN gene from both parents.
Nagashima’s parents are aging normally. Each of them has a working copy of the WRN gene, so their bodies show no signs of illness. The situation is similar with his grandfather and grandmother, who are about 90 years old. But the Japanese himself received two copies of the mutated WRN gene. Previously, at least, reliably, no one from his family came across this.
This gene was discovered only in 1996, and since then, an insignificant number of manifestations of the syndrome have been recorded. According to 2008 data (there is no more recent information), only 1,487 cases are documented in the world, 1,128 of which are in Japan. Although such statistics indicate that this is a unique phenomenon in Japan, the head of the International Registry of Werner Syndrome at Washington University, George Martin, believes that the number of real cases is about seven times higher than official figures. Most doctors simply do not know.
The imbalance of the Japanese cases is explained by two factors. First, the local mountains and islands create an insulating effect that throughout history has influenced the population – people in more remote regions in the past were more likely to have children with someone genetically similar to themselves. A similar effect on the Italian island of Sardinia, where they also recorded a group with Werner syndrome. Secondly, the development of the Japanese medical system helps to identify a rare disease more effectively than in other countries.
The University Hospital in Tiba keeps records of 269 diagnosed patients, 116 of whom are still alive. One of them is Sachi Suda (Sachi Suga), which only moves in a wheelchair. Her muscles are so weak that she can not climb or climb out of the bath alone, and the stove can stand no more than one or two minutes.
Inability to cook food, she replaces the instant soup, and then, at about 5:30 in the morning, goes to work. Three times a week she is visited by a social worker who helps her cope with pain in her legs. “Sometimes the pain is so strong that it would be better to just cut off the legs,” says the woman.
The only advantage of her condition is that in her 64 years she has already passed the average life expectancy (up to 55 years) of people suffering from Werner syndrome.
Recently, a group was set up at the University Hospital Tibe, where the carriers of the disease gather. As Souda says, talking helps alleviate pain, although at the end of the meeting the same question is always asked – “Why do I have this disease?”.
Hope for medicine
Human DNA and histones (proteins that condense chromosomes into cells) can acquire chemical labels that do not change the basis of the genes, but can drown out or enhance the activity of the gene.
Where such marks are placed and what forms they take is likely to be influenced by a person’s behavior and environment. For example, smoking or stress. Perhaps some marks appear randomly or as a result of mutations, including cancer. Scientists do not know how and why cells add these labels, but some of them are associated with aging.
Professor of Genetics and Biostatistics at the University of California, Los Angeles, Steve Horvath claims that he used one of these labels to study epigenetic clocks – a set of DNA labels that allows to determine the biological age of a tissue, cell or organ. Such tags can be read even by blood and urine samples. The study showed 18 people with Werner syndrome, their cells had a significantly higher epigenetic age than in the control group without illness.
Understanding the intricacies of aging contributes to the genetic information of Nagashima and the Courts, which they conveyed in the hope that this will be beneficial in the future.
Scientists already know that the WRN gene is the key to understanding how cells and DNA work in general. It is known that the violation of WRN leads to widespread instability of the entire gene.
The main question is whether the labels on DNA are only imprints of diseases and aging, or whether they themselves cause diseases and aging. If the latter, then the obvious question arises – is it possible to prevent or reverse part of aging or age-related disease by editing or deleting these labels?
In 2006–2007, the Japanese researcher Shingya Yamanaka received for the first time in the world induced stem cells and published studies on the fact that any adult cell can be transferred to a more earlier embryonic state, from which it can then be transformed into another cell type. For these achievements, Yamanaka received the Nobel Prize, becoming the main spring for stem cell research.
Most importantly, during the research, Yamanaka could completely erase the epigenetic marks of the cell. Researchers later repeated this in mice that suffered from premature aging syndrome. At the end of the experiments, the mice briefly rejuvenated, but died a few days later. The experiment also led to cancer and loss of cell ability to function.
In 2016, scientists from the University of California, San Diego improved their experimental methods, making premature aging slowed in test mice. The animals looked healthier and lived 30% longer than untreated mice, which also suffered from the syndrome. Moreover, in aging mice, this treatment led to rejuvenation of the pancreas and muscles.
In other words, the experiments are going actively. But one of the main questions is whether removal of epigenetic tags is associated with cell development and aging, or is it just a side effect? Professor Horvat of the University of California believes that, from an epigenetic point of view, there are obvious common features of aging in many areas of the body. Aging of the brain is similar to the aging of the liver or kidneys, because in general the aging process is quite simple, since it is reproducible in different organs.
According to Horvat, this scientific field is akin to the gold rush – everyone wants to explore it. This is not surprising, because once it was believed that a person can not change their genes, but modern science points to something else.
Shortly before the diagnosis, Nagashima was going to marry, and the girl stayed with him after the doctors’ verdict. They even passed a genetic test to make sure that they would not pass the disease on to their children. But when the bride’s parents learned about the state of the Japanese, they did not approve. On this relationship ended.
Since then, Nagashima has a new girlfriend with whom he wants to link life. True, while he lacks the courage to ask his beloved’s parents for permission. His body constantly hurts, and his limbs swell up, but he put up with it: “It hurts. But I will endure. ”