Tick-Tock: How our daily body clock protects our stem cells

In our world of tweets, tablets, smartphones and social media, it’s hard to disengage from the always-on pace of modern life. This is in stark contrast to a camping trip. After a few days in the wilderness, you adjust to a more natural sync – waking at sunrise and heading to bed at sundown. Many biological processes fluctuate along with this day/night cycle called the circadian rhythm. This 24-hour body clock is known to regulate our sleep patterns, feeding behavior, body temperature and many other functions.

Features of the human circadian (24hr) rhythm. (credit: The Gladstone Institutes)

Features of the human circadian rhythm, a 24 hr day/night body clock. (credit: The Gladstone Institutes)

Now, in a fascinating study reported last week in Cell Reports, University of California, Irvine researchers show evidence that the circadian rhythm also protects skin stem cells from damage associated with accelerated aging and cancer.

First a little background: the outer skin layer, or epidermis, contains a long-lasting population of stem cells that multiply and grow into new skin cells to keep the skin healthy and heal it from injury. In order to multiply, a cell must copy its DNA and then divide. This process requires energy that ultimately comes from the metabolic breakdown of food that we eat. Herein lies a dangerous mix: the metabolism of food that supplies energy to these cells also generates a byproduct, a very reactive oxygen molecule that damages DNA and other parts of the cell. Dividing cells are especially vulnerable to the reactive oxygen. This damage can lead to an accumulation of DNA mutations that are thought to be the underlying cause of aging and cancer.

By taking advantage of a non-invasive technique that uses sophisticated microscopes, the UC-Irvine research team examined the metabolic activity of single stem cells within the skin of live mice. They found that the metabolic step that creates these toxic oxygen molecules peaks during the daytime while previous studies have shown that the highest number of dividing cells occurs in the night. So the circadian rhythm ensures that stem cell division steers clear of the DNA damaging effects of metabolism and the two activities do not peak at the same time during the course of each day.

Dr. Bogi Anderson, UC Irvine professor of biological chemistry and medicine. (credit: Paul R. Kennedy)

Dr. Bogi Anderson, UC Irvine professor of biological chemistry and medicine. (credit: Paul R. Kennedy)

The research team, led by Bogi Andersen, professor of biological chemistry and medicine, and Enrico Gratton, professor of biomedical engineering, further shows that mice lacking Bmal1, a gene essential for the circadian rhythm, no longer have this daily metabolic fluctuation. Presumably more DNA damage would occur in these mice and in fact, other researchers have shown that mutations in Bmal1 are associated with premature aging and increased DNA damage.

Taken all together maybe there’s some truth to the idea that our frenetic modern life is dangerous for our health. As Dr. Andersen states in a press release:

“Our studies were conducted in mice, but the greater implication of the work relates to the fact that circadian disruption is very common in modern society, and one consequence of such disruption could be abnormal function of stem cells and accelerated aging. It is possible that future studies could advance therapeutic insights from this research.”

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