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Calorie restriction slows age-related epigenetic changes

Calorie restriction is known to extend lifespan in several different species. Researchers have been trying to understand how.p-e-t-e/iStock/Thinkstock

Calorie restriction has been shown to extend lifespan in several different species, but the underlying reason isn’t known. During normal aging, epigenetic changes occur throughout cells in the body. These changes alter the way genes are switched on and off without changing the DNA sequence itself. Levels of one type of epigenetic modification, called DNA methylation, have been shown to roughly reflect a person’s age.

To investigate whether caloric restriction affects DNA methylation, a team of scientists led by Dr. Jean-Pierra J. Issa at Temple University examined the epigenetic profiles of mice, rhesus monkeys, and humans at different ages. They then tested whether these changes were altered by a calorie-restricted diet in mice and monkeys. The study was funded in part by NIH’s National Cancer Institute (NCI) and National Institute on Aging (NIA). Results appeared online on September 14, 2017, in Nature Communications.

The team first analyzed DNA methylation in blood from mice, rhesus monkeys, and humans at different ages. Each species showed similar changes in DNA methylation patterns as they aged. These changes are called methylation drift, or epigenetic drift. The rates of epigenetic drift were inversely correlated with lifespan. That is, the shorter the species lifespan, the faster the changes in DNA methylation. This finding suggests that DNA methylation helps regulate the effects of aging.  

The team next tested whether a calorie-restricted diet could slow methylation drift. They fed a group of mice 40% fewer calories than controls starting when they were 0.3 years old until they were 2.7 to 3.2 years old. They also fed rhesus monkeys a diet with 30% fewer calories than controls starting at the age of 7–14 years old until they were 22 to 30 years old.

A 2009 image of rhesus monkeys in a study of the benefits of caloric restriction. The 27-year-old monkey on the left was given a diet with fewer calories while the 29-year-old monkey on the right was allowed to eat as much as it liked. Jeff Miller

The changes in DNA methylation patterns slowed for the animals fed a calorie-restricted diet. Monkeys on a calorie-restricted diet showed the same patterns of DNA methylation as monkeys who were 7 years younger but had eaten normal diets. This methylation age difference was even greater in mice.

The team next compared the rates of epigenetic drift to telomere shortening. Telomeres are molecular caps at the ends of chromosomes. Their length has previously been linked to the aging process. Calorie restriction had no measurable effect on telomere length.

“The impacts of calorie restriction on lifespan have been known for decades, but thanks to modern quantitative techniques, we are able to show for the first time a striking slowing down of epigenetic drift as lifespan increases,” Issa says.

More studies are needed to better understand why age-related epigenetic changes occur faster in some people than others—and whether altering them could help prolong human life.

—Tianna Hicklin, Ph.D.