How about the following as "news-of-the-day" - low probability that anything will come of it, but very high significance if it does:
Headline: Mouse Model Demonstrates Role of Telomeres and Telomerase in Aging,
Cancer and Lifespan
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MENLO PARK, Calif.--(BW HealthWire)--March 4, 1999--Geron
Corporation (NASDAQ:GERN) announced that researchers at the
Dana-Farber Cancer Institute of Harvard Medical School and colleagues
at Johns Hopkins School of Medicine have published in the March 5
issue of Cell that telomerase-negative mice show telomere loss with
age and experience a host of age-related changes.
This study expands on a growing body of in vivo proof that
age-related telomere erosion contributes to pathology, including
cancer. Significant new findings in this work include a causal link
between telomere loss and two hallmarks of human aging: an impaired
ability to recover from stress and an increased rate of cancer
formation. Consistent with other data linking telomerase activity with
tumor progression, the authors suggest that telomere loss contributes
to cancer formation, but lack of telomerase inhibits long-term tumor
growth.
Telomerase is an enzyme that synthesizes telomeric DNA at the
ends of chromosomes and thereby conveys extended replicative capacity
to cells. Telomerase is readily detectable in reproductive and cancer
cells. Telomerase is not detectable in most normal cells, and as a
result, telomeres shorten with cell division. Numerous in vitro and in
vivo studies have established a strong correlation between telomere
erosion and cellular aging on the one hand, and telomerase and cancer
on the other.
In a previous study (Nature: April 9, 1998), this team of
researchers led by Dr. Ron DePinho, now at Dana-Farber School of
Medicine, provided in vivo evidence that telomere erosion in the
absence of telomerase leads to progressive defects in organs with high
cell turnover. Specifically, hematopoietic, immune and reproductive
organ function had significantly declined in later generation mice.
In this study, the researchers extend their examination to the
same mice as they age within each generation. In particular, they
found that mice whose telomerase gene had been knocked out experienced
significant telomere loss and the following age-related changes:
*T
- decreased ability to recover from stress
- decreased wound healing capability
- decreased regenerative capacity of hematopoietic (blood and
gastrointestinal systems
- increased hair graying and loss
- increased ulcerative skin lesions
- increased incidence of chromosomal fusions and cancer
- decreased body weight
- decreased lifespan
*T
Further, many of these changes had an earlier onset in later
generation mice. Most importantly, each of these changes can be seen
in human aging. This provides further confirmation of the role of
telomeres and telomerase in pathology. It also provides a model system
with which modulators of telomere length can be tested.
These findings support the development of telomere length
modulators as preventive and/or corrective medicines to treat certain
age-related conditions. Accordingly, Geron is actively pursuing the
discovery of therapies that activate telomerase in normal cells, to
postpone disease, and inhibit telomerase in cancer cells to
re-mortalize tumors.
While accelerated aging was seen in numerous tissues and organs
in this study, it was not seen in all. For example, there were no
apparent signs of cataracts, osteoporosis, diabetes or vascular
disease in the telomerase-negative mice studied to date. This could be
the result of one or more factors. Perhaps it will take longer to
detect deterioration in the associated organ systems as a result of
known differences in cell division and telomere erosion rates in
different tissues. As is often the case, species differences are also
expected. For example, telomere loss may not play a significant role
in mouse vascular disease, while in much longer-lived humans evidence
already supports a role of replicative cell aging in atherosclerosis.
The findings in cancer were also interesting. The researchers
found, as others have in in vitro studies, that telomere erosion with
age in the absence of telomerase leads to an increased frequency of
chromosomal abnormalities. Further, the higher frequency of
chromosomal abnormalities strongly correlated with a higher incidence
of spontaneous tumor formation. This is consistent with the telomere
hypothesis and could explain the higher incidence of cancer among
older individuals. Conversely, the authors suggest and other studies
demonstrate, "at later points in tumor progression the absence of
telomerase inhibits long-term growth."
Calvin B. Harley, Ph.D., Geron's chief scientific officer and a
pioneer in telomere and telomerase biology, praised the quality of the
research and added, "This is a landmark study in telomere and
telomerase biology. It underscores the potential of this field to lead
to new medicines for treating various chronic, debilitating
age-related diseases including cancer." |
