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Blood Pressure Regulating System May Play Role in
Aging
Nov. 22, 2004 - The same system that regulates
blood pressure may also play a role in aging, suggesting a "whole new
mechanism" involved with aging, according to new research from Wake
Forest University Baptist Medical Center.
Four separate studies point to the
renin-angiotensin system, which helps regulate blood pressure, as also
being important in body composition, mental function and how the body
responds to exercise. The work was presented today in Washington, D.C.,
at the 57th Annual Scientific Meeting of the Gerontological Society of
America.
This is exciting because it suggests that a whole
new mechanism might be involved in aging, said Stephen Kritchevsky,
Ph.D., professor of gerontology. It offers new opportunities to explore
treatments to help older adults maintain their function.
A primary component of the renin-angiotensin system
is ACE, or angiotensin converting enzyme, which converts angiotensin I,
an inactive protein in the blood, to angiotensin II, a protein that
constricts blood vessels. Angiotensin II is balanced by another hormone
that is believed to brake high blood pressure.
Its becoming apparent that this system is
involved in more than just blood pressure, said Kritchevsky.
The Wake Forest Baptist research is the first to
show that the system may be associated with physical function in older
adults. The projects are:
* Mobility and ACE A common variant of the gene
that controls ACE production can be inherited in three different
combinations. In a study that involved more than 3,000 well-functioning
adults, ages 70 to 79, researchers investigated how the variant affects
response to exercise. Half of the group was active, burning more than
1,000 calories a week in exercise; the other half was inactive.
All exercisers had better mobility than
non-exercisers, but exercisers who had the gene combination associated
with the lowest ACE production were 47 percent more likely to become
limited in their mobility than exercisers with the combination
associated with the highest ACE production. Kritchevsky, who led the
study, said ACE production was associated with how well activity helped
preserve function.
* Strength and ACE The physical function of 211
obese, sedentary adults, ages 60 and older, was assessed before and
after 18 months of exercise. Before exercise began, no association was
found between the particular combination of the ACE gene variant and
participants knee strength, ability to walk 6 minutes, or level of body
fat.
At the end of the program, however, participants
with the combination associated with highest ACE production showed a 75
percent improvement in knee strength compared to a 23 percent
improvement in participants who had the combination associated with
lowest ACE production. There were no differences in walking distance
between the two groups.
Changes in muscle strength with exercise training
in older individuals may be dependent on ACE genotype, said Barbara
Nicklas, Ph.D., associate professor of gerontology, who led the study.
Kritchevsky said researchers dont yet understand
how ACE levels affect physical and mental function. He said knowing more
about the biochemical pathways of ACE may help explain two additional
studies in animals with seemingly contradictory results.
The results pose a bit of a puzzle, but underscore
the need to learn more about how this system influences human health,
he said. The animal studies were:
* ACE and Body Composition Previous studies
showed that ACE inhibition might improve body composition and physical
performance. Christy Carter, Ph.D., assistant professor of gerontology,
tested this finding in 24-month old rats, approximately equivalent in
age to 60-year-old humans. Half of the animals were treated with a blood
pressure drug that inhibits ACE production. The other half got an
inactive treatment. After six months, the animals that got the inactive
treatment had greater declines in strength and physical performance. The
animals treated with ACE inhibitors had lower body weight, despite the
fact that the two groups had equal food intake.
ACE inhibition may prevent age-related decline in
physical performance, perhaps through a reduction in total fat mass,
said Carter.
* ACE and Cognition: Radiation is often the best
treatment for brain tumors, but it can result in permanent and
progressive cognitive impairment. Mike Robbins, Ph.D., professor of
radiation oncology, said that in essence, radiation mirrors the effect
of the brains aging process. Researchers believe the underlying cause
is oxidative stress, the inability of a cell to remove free radicals, or
molecules with unpaired electrons, that can damage cells.
In rats, Robbins tested a blood pressure medication
that blocks the effects of angiotensin II. Early results show that the
drug has the potential to combat oxidative stress and reduce cognitive
impairment.
About Wake Forest University Baptist Medical
Center: Wake Forest Baptist is an academic health system comprised of
North Carolina Baptist Hospital and Wake Forest University School of
Medicine. It is licensed to operate 1,282 acute care, psychiatric,
rehabilitation and long-term care beds and is consistently ranked as one
of Americas Best Hospitals by U.S. News & World Report.
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