Every person, every mouse, every dog, has one surefire sign of aging: hair loss. But why does this happen? Rui Yi, a professor of pathology at Northwestern University, set out to answer this question.
The generally accepted hypothesis about stem cells states that they replenish tissues and organs, including hair, but that they will eventually deplete and then die in their place. This process is seen as an integral part of aging.
Instead Yi and his colleagues made a surprising discovery that, at least in the hair of aging animals, stem cells escape from the structures that house them.
“It’s a new way of thinking about aging,” said Dr. Cheng-Ming Chuong, a skin cell researcher and professor of pathology at the University of Southern California, who was not involved in Yi’s study, which was Published on Monday in the magazine Nature Aging.
The study also identified two genes involved in hair aging, opening up new possibilities for stopping the process by preventing stem cells from escaping.
Stanford University stem cell researcher Charles KF Chan called the paper “very important,” noting that “in science, everything about aging seems so complicated that we don’t know where to start.” By showing a pathway and a mechanism to explain aging hair, Yi and his colleagues may have provided a toe.
Stem cells play an important role in hair growth in mice and humans. Hair follicles, the small tunnel-shaped organelles from which hair grows, go through a cyclical period of growth in which a population of stem cells residing in a particular area called the bulge and become the rapidly growing hair cells.
Sarah Miller, director of the Black Family Stem Cell Institute at the Icahn School of Medicine at Mount Sinai, who was not involved in Yi’s paper, explained that those cells give rise to the hair shaft and its sheath. Then, after a period of time, which is short for a human body hair and too long for a hair on a person’s head, the follicle becomes dormant and its underside is damaged. The hair shaft stops growing and is shed, only to be replaced by a new strand of hair as the cycle repeats.
But when the rest of the follicle dies, a collection of stem cells remain in the bulge, ready to begin turning into hair cells to grow a new strand of hair.
Like most scientists, Yee held that stem cell death occurs with age in a process known as stem cell exhaustion. They hoped that the death of the stem cells of the hair follicle meant that the hair would turn gray and that when enough stem cells were lost, the hair strand would die. But this hypothesis was not fully tested.
Together with a graduate student, Chi Zhang, Yi decided that in order to understand the aging process in hair, they needed to look at individual strands of hair as they got older.
Typically, researchers studying aging take tissue fragments from animals of different ages and examine the changes. There are two drawbacks to this approach, Yi said. First, the tissue is already dead. And it is not clear what changes have been observed or what will come after them.
He decided that his team would use a different approach. They observed the growth of individual hair follicles in the ears of mice using a long-wavelength laser that can penetrate deep into the tissue. They labeled the hair follicles with green fluorescent protein, anesthetized the animals so they wouldn’t move, put their ears under the microscope and went back again and again to see what was happening to the same hair follicles.
What they saw was a surprise: When the animals started getting old and gray and lost their hair, their stem cells began to grow out of their tiny homes in bulges. The cells change their shape from round to amoeboid and squeeze through tiny pores in the follicle. Then they regained their normal size and walked away.
Sometimes, the escaping stem cells leap long distances from where they lived, in cellular terms. “I wouldn’t have believed it if I hadn’t seen it for myself,” Yi said. “It’s almost crazy in my mind.”
The stem cells then disappeared, probably consumed by the immune system.
Chan compared the body of an animal to a car. “If you drive it long enough and don’t change parts, things get screwed up,” he said. In the body, stem cells are like a mechanic, providing replacement parts, and in some organs such as hair, blood, and bone, replacement is continuous.
But with hair, it seems that the mechanic – stem cells – just gets fired from the job one day.
genes and hair loss
but why? The next step by Yi and his colleagues was to ask whether genes were controlling the process. They discovered two — FOXC1 and NFATC1 — that were less active in older hair follicle cells. Their role was to imprison the stem cells in the bulge. So the researchers bred mice that lacked those genes to see if they were the master controllers.
By the time the mice were 4 to 5 months old, their hair had started to fall out. By the age of 16 months, when the animals were middle-aged, they looked pristine: they had lost a lot of hair and the rest had turned gray.
Now researchers want to save hair stem cells in aging mice.
This story of discovering a completely unexpected natural process leaves Chuong wondering what remains to be learned about living beings.
“Nature has infinite wonders that await us,” he said. “You can see great things.”
This article is originally from . appeared in the new York Times.
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