A Gene Tweak Could Keep Heart Young

ByABC News
October 12, 2009, 5:23 PM

Oct. 13 -- MONDAY, Oct. 12 (HealthDay News) -- Japanese scientists have prevented age-related deterioration in the hearts of mice by suppressing the activity of a gene involved in the insulin-signaling system that helps regulate the life span of cells, and they say the finding is potentially applicable to the control of heart failure in humans.

"A lifelong genetic modification of the human heart is not possible," said Dr. Tetsuo Shioi, an assistant professor of medicine at Kyoto University Graduate School of Medicine, and lead author of the report in the Oct. 12 online edition of Circulation. "However, drugs that lower insulin are available and can prevent cardiac aging, increase exercise tolerance and reduce heart failure in middle-aged to aged members of the population."

Shioi and his colleagues have been working with the phosphoinositide-3-kinase (PI3K) gene, which is the subject of intense activity in many U.S. and foreign laboratories. The gene plays an important role in both the aging and proliferation of cells, and research is aimed at developing gene therapy not only for heart disease but also for some forms of cancer.

The Japanese study used elderly mice that were genetically engineered to suppress the activity of one form of the PI3K gene. That variant, called the p110alpha isoform, plays an important role in tissue aging. Previous studies have shown that suppressing the variant's activity extends the life of one species of roundworm and prevents the age-related decline of heart function in fruit flies.

In the study, the researchers found that older mice with suppressed p110alpha activity had better cardiac function, fewer biological markers of aging, less of the fibrosis that can reduce heart function and, in general, a pattern of heart gene activity seen in younger mice, compared to those with normal gene function.

"Our paper indicated that insulin signaling is a conserved and important mechanism that regulates cardiac aging," Shioi said. "Thus, it is highly likely that our result can be translated to the prevention of cardiac aging and heart failure in the aged human population."