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Hair Loss News Archives
March 2007
Scientist Discover the Cellular Roots of Graying Hair
Findings Could Shed New Light on Malignant Melanoma
Few things about growing older are as inevitable and obvious as ''going gray,''
yet scientists have been unable to explain the precise cause of this usually
unwelcome transformation.
In a report posted today on the Web site of the journal Science, researchers
from Dana-Farber Cancer Institute and Children's Hospital Boston say they have
found the cellular cause of graying hair while investigating the origins of
malignant melanoma, the potentially deadly skin cancer.
The scientists traced the loss of hair color to the gradual dying off of adult
stem cells that form a reservoir that spawns a continuous supply of new
pigment-manufacturing cells, called melanocytes, that give hair its youthful
hues.
Not only do the non-specialized stem cells become depleted: They also
progressively make errors, turning into fully committed pigment cells in the
wrong place within the hair follicle, where they are useless for coloring hair.
The new findings won't lead to a scientific alternative to hair dyes any time
soon, if ever, even if they do solve a longstanding puzzle about the underlying
mechanism of graying.
Of more interest to the researchers is the pattern of cellular signals that
triggers the death of pigment stem cells, since melanoma is dangerous for the
opposite reason - melanocytes proliferate uncontrollably to form tumors and are
hard to kill with treatment.
''Preventing the graying of hair is not our goal,'' emphasizes David E. Fisher,
MD, PhD, director of the Dana-Farber Program in Melanoma, and senior author of
the Science paper. ''Our goal is to prevent or treat melanoma, and to the extent
this research is revealing the life cycles of melanocytes, which are the cells
that become cancerous in melanoma, we would love to identify a signal that would
make a melanoma cell stop growing.''
Fisher and the report's lead author, Emi K. Nishimura, MD, PhD, also of the
melanoma program, are in the Department of Pediatric Oncology at Children's
Hospital Boston as well as at Dana-Farber. The second author, Scott R. Granter,
MD, is a pathologist at Brigham and Women's Hospital.
The American Cancer Society expects about 55,100 people to be diagnosed with
melanoma, the most serious form of skin cancer, in 2004, with an estimated 7.910
deaths.
Melanoma can be cured when it is detected and treated early, but if the
lesion penetrates deeply into the skin it is often fatal. Sun exposure is a
major risk factor in the disease, which has been increasing in the past several
decades.
Melanocytes, which manufacture and store the pigment that combines with
hair-making cells called keratinocytes to color the hair, are specialized cells
spawned by colorless melanocyte stem cells. These cells were discovered by
Nishimura in 2002.
A pool of undifferentiated melanocyte stem cells resides in the hair follicle,
and during the hair's grow-and-rest cycle, the stem cells give rise to
color-making melanocytes that journey to the bottom of the hair follicle: That
is where they tint the keratinocytes with the person's characteristic hue.
By studying mice at progressively older intervals, Fisher and his colleagues
discovered that as the rodents aged and their hair began turning gray, the
numbers of stem cells diminished in proportion to the loss of color.
The scientists were surprised to observe that, at the same time and the same
rate, differentiated, pigmented melanocytes were showing up in the follicle at
the location where the stem cells resided.
Since they were in the wrong place, the pigmented cells likely did nothing to
maintain the mice's hair color.
To see if the cells behaved the same way in humans, the investigators examined
human scalp tissue taken at increasing ages, and determined that the same
pattern occurred.
Since cell survival in general is influenced by an ''anti-death'' gene called
Bcl2, Fisher's team analyzed mice lacking this gene. In a dramatic fashion, the
mice lost their melanocyte stem cells shortly after birth and quickly went gray.
It may be that people who gray prematurely have mutations that knock out Bcl2
activity, Fisher says.
''This tells us there is a requirement for Bcl2 in normal hair follicle
cycling,'' adds Fisher. ''So the question is: what in the hair follicle is
signaling the stem cells that is absent when aging occurs and the stem cells die
off. Now we have a much more refined way of dissecting that signaling pathway in
melanoma.
Eventually we hope to tap into this death pathway, thereby using drugs to
mimic the aging process, to successfully treat melanoma.''
The team also made mice lacking a gene, MITF that regulates Bcl2. These mice
also went gray, but more gradually than did the mice that had no Bcl2. The loss
of MITF activity, the investigators say, appears to be implicated in the
mistaken differentiation of melanocyte stem cells that accompanies the stem
cells' depletion. MITF, they conclude, seems to play a crucial role in
maintaining the supply of stem cells within the hair follicle, and graying is
the result of ''incomplete maintenance of melanocyte stem cells.''
The research was supported by the National Institutes of Health, and Nishimura
received funding from The Shiseido Award in 2002 and The Charles A. King Trust
of Fleet National Bank and The Medical Foundation.
Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard
Medical School and is among the leading cancer research and care centers in the
United States. It is a founding member of the Dana-Farber/Harvard Cancer Center
(DF/HCC), designated a comprehensive cancer center by the National Cancer
Institute.