You are hereAugust 16, 2017
Aging is exacerbated by alterations of stem cell circadian rhythm
Many researchers believe that with the passage of time, stem cells cease to differentiate between day and night cycles – in other words they lose their circadian rhythm and this loss promotes aging. However, two studies reject this hypothesis. During aging, the researchers conclude, stem cells continue to show rhythmic activity but reprogram their circadian functions.
"Aged stem cells conserve circadian rhythm but now perform another set of functions to tackle the problems that arise with age," explained Salvador Aznar Benitah, Ph.D., head of the Stem Cells and Cancer group at the Institute for Research in Biomedicine (IRB Barcelona) and leader of the two studies. The scientists do not know how such reprogramming comes about. “The problem is that as they age, stem cells lose the rhythmic functions necessary for tissue protection and maintenance, which become replaced by functions aimed at coping with stress,” he added. “Loss of the previous circadian functions of stem cells during natural ageing contributes in some way to greater damage and greater aging."
The first authors of both studies – associate researcher Guiomar Solanas, Ph.D., and doctoral student Francisca Oliveira Peixoto, both at IRB Barcelona – compared stem cells from young mice (three months old) with those of aged mice (between 18 and 22 months old) in skin, muscle and liver tissue every four hours over one day. "The experiments have been technically highly complex and demanding, but the results are surprising," said Dr. Solanas.
Gene reprogramming occurs, for example, in response to accumulated DNA damage, inflamed tissues and an inefficient cell self-cleaning process (autophagy).
"Although aging always involves circadian reprogramming, an interesting aspect of our results is that such reprogramming is specific and distinct for each type of tissue studied. This observation implies that although the entire organism is aging, each tissue goes through this process in a different way. So to address the slowing down of aging, it will be necessary to study each tissue separately," explained Pura Muñoz-Cánoves, Ph.D., with the Department of Experimental and Health Sciences at the Pompeu Fabra University and co-author of one of the studies.
A low-calorie diet keeps the circadian rhythm young
A low-calorie diet is known to delay the signs of aging in primates and mice. In another set of experiments, Drs. Solanas and Peixoto gave mice a low-calorie diet for six months and compared them with counterparts on a normal diet. The animals on the low-calorie diet conserved most of the rhythmic functions of their youth.
"The low-calorie diet greatly contributes to preventing the effects of physiological aging. 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 tissues. Eating less appears to prevent tissue aging and therefore prevents stem cells from reprogramming their circadian activities," Dr. Aznar Benitah explained.
According to the researchers, their studies would explain why a calorie restrictive diet slows down aging. What is not clear is whether low-calorie diets would keep aging at bay in humans.
"Such diets are unlikely to become widely followed because they entail constant hunger and require a lot of willpower; also, such eating regimes provide the body with the minimum energy to perform its basic functions, which in the long term may have negative effects on people's everyday lives," stressed Dr. Aznar Benitah. In this regard, he explained, it is 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.
Both studies were published August 10 in Cell.
Shown is DNA damage accumulation (in green), seen in old mice skin. Credit: Guiomar Solanas and Francisca Peixoto, IRB Barcelona