Certain gene variation associated with better mobility for older individuals who exercise

Older individuals with a certain gene variation who exercise are less likely to develop mobility limitations than individuals without the gene variation, according to a study in the August 10 issue of JAMA: The Journal of the American Medical Association.

Mobility limitation (i.e., difficulty walking and climbing steps) is common and is strongly related to major health outcomes, and may represent a stage in the disablement process amenable to intervention, according to background information in the article. Approximately 34 percent of the U.S. population 70 years and older report walking limitations, i.e., difficulty walking a quarter mile. Those reporting such difficulty are at nearly 4 times the risk of nursing home placement and 3 times the risk of death over 2 years compared with those reporting no difficulty. In older adults, more physical activity is consistently associated with less functional decline.

Despite exercise's general benefit, individual responses to exercise vary. The basis for this is unclear, but there appears to be a strong genetic component. A certain gene variation (an insertion [I]/deletion [D] polymorphism in intron 16 of the angiotensin-converting enzyme [ACE]) gene has been identified as a potential marker for differential response to exercise in younger adults.

Stephen B. Kritchevsky, Ph.D., of the Wake Forest University School of Medicine, Winston-Salem, N.C., and colleagues examined the interrelationship between ACE I/D genotype, high levels of physical activity, and functional decline, defined as the incidence of mobility limitation. The Health Aging and Body Composition (Health ABC) Cohort Study, conducted in the metropolitan areas of Memphis, Tenn., and Pittsburgh, Pa., included 3,075 well-functioning community-dwelling adults aged 70 through 79 years. The participants were enrolled from 1997 to 1998 and had an average follow-up of 4.1 years. Mobility limitation, which 1,204 participants developed, was defined as difficulty walking a quarter of a mile or walking up 10 steps, as reported on 2 consecutive semi-annual interviews.

"In this cohort of older well-functioning men and women, a high level of physical activity was associated with the preservation of physical function. Although physical activity was associated with less mobility limitation for all ACE I/D genotypes, the improved risk benefit was significantly greater for those possessing the ID or DD genotypes compared with the II genotype. The physiological basis for these findings is uncertain. However, among the physically active participants, the II genotype was also associated with higher levels of total adiposity [body fat] and intermuscular thigh fat," the authors write.

"… the magnitude of the effect is not so strong as to imply that those possessing the II genotype do not benefit from exercise. Further study is required to confirm these associations and understand their physiological basis," the authors conclude. (JAMA. 2005; 294:691–698.