telomerase, independent of telomere function, activates hair follicle stem cells
Kofi
frivolous for focusing on hair follicle stem cell growth. I think this
research establishes why follicles are worthy of study in the context of
human aging.
A few notes of interest:
Stress may affect telomerase. Mothers of chronically ill children have
less active telomerase and the stress amounts to an additional decade of
aging. <http://www.sciencedaily.com/releases/2004/11/041130080802>.
Retinoic acid extends the life of keratinocytes (hair support cells) via
p16 and telomerase [PMID 14654966].
I also seem to recall carnosine inducing telomerase. I'd look it up and
give you a citation but PubMed is spittin' hissies right now (I think
I'm thinking of PMID 15474517 but that may not be it). Presuming time
has not completely dulled my once polished intellect, IGF-I is an adult
stem cell recruitment signal sent out by damaged tissues, zinc
L-carnosine induses IGF-I in the gut [PMID 11208487], both zinc
L-carnosine [PMID 15010260] and regular carnosine [PMID 15102049]
promote factors which repair ligaments and collagen-producing tissues
(BMP-2/BMP-7) - tissues harmed by IGF-I deficiency. I suspect a
connection.
Unless there isn't one.
<http://www.nytimes.com/2005/08/18/science/18cell.html>
Furrier Mice Yield Stem-Cell Discovery
By NICHOLAS WADE
Published: August 18, 2005
By making mice grow furrier coats, researchers have discovered that an
enzyme known to serve as a last-ditch defense against cancer also
activates adult stem cells, which the body uses to repair its tissues.
The insight could lead to new treatments for certain diseases, possibly
even promoting hair growth in animals other than mice.
The research, reported by Steven E. Artandi and colleagues at Stanford
University in Nature today, shows that adult stem cells can be activated
by an enzyme called telomerase.
The finding is surprising because telomerase is well known in a quite
different context, protecting against tumors by limiting the number of
times a cell can divide. The new findings put the enzyme astride two
major biological pathways, one that promotes the growth of new cells for
maintaining tissues and the other that prevents the excessive growth
that leads to tumors.
The finding is "very interesting and very tantalizing," said Carol
Greider, a telomerase expert at the Johns Hopkins University, who was
not involved in the research.
Dr. Artandi chose to study the effects of telomerase on mouse fur not to
develop a Rogaine for rodents, but because mice have an easily
accessible stem cell system built into their skin. Each hair follicle
has attached to it a small bulb full of stem cells. When the stem cells
are activated, the follicle grows a new hair shaft.
Dr. Artandi's team genetically engineered a strain of mice in which the
telomerase gene could be turned on with a drug. When the mice were given
this drug, the stem cells in their hair follicles proliferated, and the
mice grew extra furry coats.
The usual role of telomerase is to maintain the telomeres, special
lengths of DNA that cap each end of the chromosomes. But it performs
this service only for egg and sperm cells and to some extent for stem
cells.
The telomerase gene is switched off almost entirely in normal cells. So
each time a normal cell divides, its telomeres become shorter, and after
they dwindle to a certain length, the cell is forced into senescence and
cannot divide again.
For several years, there have been hints that the telomerase protein
performs some role other than just maintaining telomeres. Dr. Artandi
said he had decided to look for that role in stem cells, because the
gene that makes the enzyme is active in these cells.
To avoid confusion with the telomere-lengthening role of telomerase, he
engineered the mice to lack the additional biochemical machinery needed
to maintain telomeres. Thus when the mice were fed the
telomerase-activating drug, the telomerase must have activated the stem
cells in some way that did not involve their telomeres.
Dr. Artandi said he did not yet know how telomerase activated stem
cells. But when this new pathway is understood, it may suggest ways of
tackling diseases in which the right cells fail to proliferate like
pancreatic islet cells in diabetes.
Normal male mice do not go bald as they age, but the research could
still be significant for human beings. Anthony Oro, a dermatologist and
co-author of the report, said the great challenge in male-pattern
baldness was how to restart the arrested follicles.
The finding about telomerase in mice "doesn't prove that this is the
master regulator of all hair follicle cycling," Dr. Oro said, but it
helped define the players.
Telomerase experts not involved in this study are enthusiastic about the
finding, which opens out an unexpected line of inquiry about their
favorite gene. "I think it is an extremely important observation," said
Ron DePinho of the Harvard Medical School.
Elizabeth Blackburn of the University of California, San Francisco, said
that "biologically it's intriguing" that telomerase should have two such
different roles. But, Dr. Blackburn added, it is too early to know
whether this is just one of nature's frequent economies in using the
same protein to do two things.