For most of us, our body follows a predictable timeline when it comes to growing older. While there’s some variation depending on genes and lifestyle, each year, we age with a relative consistency to the rest of the population, our physical form maturing in sync with our age cohort. For Nobuaki Nagashima, aging moves at a different pace.
The Case of Nobuaki Nagashima
Nagashima has a rare genetic disorder called ‘Werner syndrome’ which causes the body to age at an accelerated rate. Symptoms slowly appear after adolescence, with those affected usually diagnosed in their twenties. All of the external bodily changes we expect later in life- wrinkles, hair loss, greying- appear at much younger ages. Internally, the body ages too, which affects the heart, arteries, and causes other medical conditions such as cancer.
Nagashima was diagnosed in his twenties and experienced a decline in health over the next 20 years that has incapacitated him from participating much of his life from before. Now at age 43, his life is filled with visits to the hospital to treat frequent ailments. After undergoing numerous surgeries, he left his position in the military for work that’s more accessible. While he continues to work temporarily at the city hall, the disorder has never been easy. Since his diagnosis, he has struggled to move the way he used to. He also lost the women he hoped to marry because her parents disapproved of the couple, due to the disease. Additionally, he has cataracts, replaced hips, and struggles to walk as he used to. Other patients report similar difficulties, with patients describing the extra time and effort it takes to move around the house, cook, stand for any period of time, or maintain independence.
The disease is recessive, meaning both parents must pass on the mutated gene for their child to express the disorder. Nobody in his family has been affected by the disorder before him, and although his grandparents all continue to live into their 90s, because each relative still possessed a healthy gene. Nagashima inherited the mutated gene, WRN, from both sides of the family, unfortunately inheriting Werner syndrome in the process.
The condition is largely contained to Japan, with 76% of the recorded 1,487 cases from the country. However, it’s speculated that the disease is largely undiagnosed. Many doctors aren’t familiar with the rare disorder that was only discovered in 1996. It’s suggested the disease mostly affect the Japanese population due to their geographical isolation, which creates an insulated genetic pool, as well as because Japan’s high frequency means that their medical community has higher awareness of the disease, which means fewer cases go undiagnosed.
Stem Cell Research Break-Throughs
There is excitement in the scientific community about new stem cell research that has began to potentially unlock secrets about how our DNA and genes age and thus, how to control it. This could provide insights that may help Nagashima and the rest of the population manage Werner syndrome.
DNA is affected over time. Though the genes are static, there are epigentic markers that determine which parts of them are expressed or kept dormant are affected by life experience, and respond over time to the environment. Life conditions imprint marks on our cells that develop over time, such as ‘methyalation marks’ which affect how the genes are then expressed. These marks are being used to study Werner syndrome. Professors at UCLA have been studying aging through these more nuanced epigenetic markers that occur inside the body to study one’s epigenetic age, rather than basing the study on physiological symptoms. The cells of people with Werner syndrome show the same story: their cells are aging at much faster rates, though it is unclear why the marks develop. It could be that they are caused by the aging, but they inversely could be the cause of it. This is a question of great significance to the researchers. If it is the epigenetic markers that cause the aging, researchers hope they could be tinkered with using epigenetic editing tools.
As of now, research on stem cells that came out from Japan in 2006 has found a way to turn back the epigenetic age of adult stem cells. They move the stem cells to their prenatal stage, removing the marks that develop with age. This promising research led the Japanese scientist Shinya Yamanaka to win the Nobel Prize, after he found four genes which can be tinkered with to turn back the cell’s clock. While extremely exciting research, at this point in time, the experiments have still only been done with mice. It has also showed to damage the cells abilities and lead to other health conditions. However, related research has been conducted, since the process has prolonged the lives of mice with different disorders and gave a better quality of life.
This stem cell research affects a wide range of genetic disorders– and it also impacts a fundamental question of humanity: what it means for our bodies to grow older. For people like Nagashima, this research could enable him to live a life without setbacks, to keep him on the same track as his peers. For the rest of the population, this research also presents questions about the very nature of bodies, which are also aging– even if the pace is slower.. If we can tinker with our aging, we tinker with our body’s relationship to time.
Interested in learning more about Nobuaki Nagashima? Read more in the source article at Qrius.
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