Cutting calories slows aging of the heart

MADISON – To remain young at heart, eat less.

That, in short, is the message drawn from research published today, Oct. 28, by a team of researchers from the University of Wisconsin-Madison.

Writing in the Proceedings of the National Academy of Sciences (PNAS), a research group led by UW-Madison genetics Professor Tomas A. Prolla, and Medical School Professor Richard Weindruch, reports the results of a study in which middle-aged mice, put on a calorie-restricted diet, exhibit signs of a remarkable uptick in heart health in old age.

“It looks like caloric restriction just retarded the whole aging process in the heart,” said Prolla whose group employed powerful molecular techniques to study nearly 10,000 genes at work in the heart. The work represents the first global analysis of gene expression in the aging heart.

Results from the PNAS study, conducted by Prolla and Weindruch with colleagues Cheol-Koo Lee, also of UW-Madison, and David Allison and Jaap Brand of the University of Alabama at Birmingham, provide new insight into the pattern of genetic change that occurs in heart cells as the organ ages, and how those changes can be mitigated by eating less.

Importantly, the study identifies genetic pressure points for stemming age-related heart disease, long the No. 1 cause of death in the United States. Such knowledge can help pharmaceutical companies identify medicines that may be able to prevent the genetic changes that underlie heart disease.

Caloric restriction, where diets remain nutritious but are reduced in calories, is the only known way to extend life span. Numerous studies, including studies of primates, mice, spiders and other animals, have demonstrated significant health benefits and a general slowing of the aging process. In some instances, the life span of experimental animals has been increased by as much as a third. In 1982, Weindruch and his colleague Roy Walford discovered that caloric restriction, begun in middle age, could extend the life span of mice by up to 20 percent.

According to Prolla, the new study provides compelling evidence that — even starting in middle age — cutting calories can confer significant health benefits for the heart and extend its working life. It does so, according to the study’s results, by exerting influence on the genetic program that governs heart cells.

In animals on a full diet, aging appears to alter the activity of a series of genes — activating some and turning others off — that affect the ability of the hardest working cells in the body to carry out their functions and remain healthy over time. The Wisconsin group observed genetic changes with aging, for example, that effectively shift the source of energy for heart cells and damage their ability to communicate with the central nervous system.

Moreover, genes that play a role in increasing the size of heart cells, a condition that often precedes heart disease, come into play as the hearts in animals on a regular diet age, Prolla said.

But in mice on a restricted diet, many of the age-related genetic changes observed in animals on a normal diet were prevented. Caloric restriction, among other things, inhibited the genes involved in cell death and that prompt inflammation, suggesting that the heart cells of animals on a restricted calorie diet are healthier overall.

“The most surprising thing to me,” said Prolla, “is that caloric restriction, even when started in middle age, has a very strong effect on changes that occur with aging.”

The work strongly suggests, Weindruch added, that influencing the genetic events that occur with aging — whether through dietary restriction started in middle age or through new drugs — can retard aging of the heart.

The Wisconsin study was conducted using “gene chip” technology, which permits scientists to assess the activity of thousands of genes at once. The gene-scanning technique can rapidly scan DNA to assess changes in gene activity, and provide clues to how genes function and turn on and off over time.
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