Scientists studying how aging affects the biological clock's control of metabolism have discovered that a low-calorie diet helps keep these energy-regulating processes humming and the body younger.

In a study published in the journal Cell, researchers reveal how circadian rhythms - or the body's biological clock - change as a result of physiological aging. The clock-controlled circuit that directly connects to the process of aging is based on efficient metabolism of energy within cells.

The team tested the same group of mice at 6 months and 18 months, drawing tissue samples from the liver, the organ which operates as the interface between nutrition and energy distribution in the body. Energy is metabolized within cells under precise circadian controls.

The researchers found that the 24-hour cycle in the circadian-controlled metabolic system of older mice remained the same, but there were notable changes in the circadian mechanism that turns genes on and off based upon the cells' energy usage. Simply put, the older cells processed energy inefficiently.

"This mechanism works great in a young animal, but it basically shuts off in an old mouse," senior author said.

However, in a second group of aged mice that were fed a diet with 30 percent fewer calories for six months, energy processing within cells was more than unchanged.

Authors show that calorie restriction results in an enrichment in SIRT1 targets in the liver. This is accompanied by distinct circadian hepatic signatures in NAD⁺-related metabolites and cyclic global protein acetylation. Strikingly, this oscillation in acetylation is absent in old mice while calorie restriction robustly rescues global protein acetylation.

"In fact, caloric restriction works by rejuvenating the biological clock in a most powerful way," senior author said. "In this context, a good clock meant good aging."

The team tested body clock functioning in stem cells from the skin of young and older mice. They too found that a low-calorie diet conserved most of the rhythmic functions of youth"The low-calorie diet greatly contributes to preventing the effects of physiological aging," said the co-lead. "Keeping the rhythm of stem cells 'young' is important because in the end these cells serve to renew and preserve very pronounced day-night cycles in tissue. Eating less appears to prevent tissue aging and, therefore, prevent stem cells from reprogramming their circadian activities."

According to the researchers, these studies can help explain why a calorie-restricted diet slows down aging in mice. The implications for human aging could be far-reaching.

The scientists said that it's important to further examine why metabolism has such a dominant effect on the stem cell aging process and, once the link that promotes or delays aging has been identified, to develop treatments that can regulate this link.

It's been shown in previous fruit fly studies that low-calorie diets can extend longevity, but the currentresearch is the first to show that calorie restriction influences the body's circadian rhythms' involvement with the aging process in cells.

"These studies also present something like a molecular holy grail, revealing the cellular pathway through which aging is controlled," senior author said. "The findings provide a clear introduction on how to go about controlling these elements of aging in a pharmacological perspective."
 
https://news.uci.edu/2017/08/10/link-between-biological-clock-and-aging-revealed/

http://www.cell.com/cell/fulltext/S0092-8674(17)30878-4?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867417308784%3Fshowall%3Dtrue