System That Regulates Blood Pressure May Also Affect Aging

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, 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.

"It's 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 don't 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 speeds up the brain's aging process. Researchers believe the 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.