Slip, slop, slap — and avoid midnight snacks

In recent years, various studies have been conducted into the time at which we consume our meals and the effect that this has on our bodies. But I bet you never thought your mealtimes could affect the biological clock of your skin — or its ability to protect itself from the sun’s rays.

Researchers from UT Southwestern Medical Center and UC Irvine recently became intrigued by the prospect that the signals that influence circadian clocks, such as time of feeding, could act as a regulator of skin function. They focused on feeding time because this was already known to affect the daily cycles of metabolic organs such as the liver.

The researchers decided to investigate this phenomenon in mice — usually nocturnal animals — over a period of 25 days, with the results published in the journal Cell Reports.

“Despite the circadian clock’s multiple roles in skin biology … little is known of the factors that entrain the skin circadian clock,” the study authors wrote. “Restriction of food intake to defined time periods is known to change the phase of the circadian clock and gene expression programs, especially in primary metabolic organs such as the liver.

“But not all peripheral tissues are entrained by RF [time-restricted feeding] and the effect of RF on the skin has not been investigated. Hence, we examined whether RF can entrain the circadian clock in skin and affect skin function.”

Led by Dr Joseph S Takahashi, chairman of neuroscience at UT Southwestern Medical Center’s Peter O’Donnell Jr. Brain Institute, the researchers split their mice into five different groups with five different feeding schedules. The ad libitum (AD) group of mice had unlimited access to food; the early daytime (ED) group had access to food from Zeitgeber time (ZT) 0 for four hours; the midday (MD) group had access from ZT5 for four hours; the early night-time (EN) group had access to food starting at ZT12; and the long daytime (LD) group had access from ZT3 for eight hours.

The team determined the mice’s circadian clock phase by analysing the peak time of skin mRNA expression of Per2, a commonly used indicator of circadian phase. And while mice fed during the night (EN) were found to have a Per2 phase equivalent to the AD group, there was significant variation between the other groups.

“MD induced a phase advance on average of 4.19 ± 0.43 hr; in contrast, ED caused a phase delay on average of 4.72 ± 0.38 hr. The phase of Per2, then, was almost 9 hr apart for MD and ED, the groups with the most widely separated phases. The magnitude of phase advances was the same in LD and MD,” the researchers wrote. They also found that the amplitude of Per2 was significantly lower in day-fed mice compared with EN; using AD/EN as a reference, the phase shift of Per2 in ED was significantly different compared with LD and MD.

So this proves that there was a definite difference in circadian rhythm, but how exactly did this manifest itself? The researchers found that the expression of around 10% of the genes in the mice’s skin, including those involved in oxidative-reductive metabolism and cell proliferation, responded acutely to food intake, and that the metabolic status of skin was determined by feeding. The most interesting aspect of their results, however, came down to a shift in the skin’s sensitivity to UV damage.

Previous work in mice had shown that sensitivity to UVB-induced DNA damage in the epidermis is diurnal, with more damage when UVB rays are applied during the night than during the day. To test whether daytime feeding, with its consequent shift in the phase of the circadian clock, modulated epidermal sensitivity, the researchers applied UVB rays during both the day and night to the shaved backs of AD, EN, ED and MD mice, collecting the skin 15 minutes after exposure.

Consistent with previous studies, mice that ate mainly (AD) or only (EN) at night formed more cyclobutane pyrimidine dimers (CPDs) — the primary cause of melanomas in humans — when exposed to UVB during the night rather than during the day. However, mice fed during the day (ED and MD) sustained more skin damage when exposed to UVB light during the day rather than during the night.

“Thus … daytime RF reverses the diurnal rhythm of sensitivity to UVB-induced DNA damage,” the study authors wrote.

According to the researchers, this outcome occurred, at least in part, because an enzyme that repairs UV-damaged skin — xeroderma pigmentosum group A (XPA) — shifted its daily cycle to be less active in the day. Mice that were fed only during their usual evening times did not show altered XPA cycles and were thus less susceptible to daytime UV rays.

Nevertheless, the researchers were somewhat taken aback by the news, with Dr Takahashi – something of an expert on circadian rhythm — saying, “This finding is surprising — I did not think the skin was paying attention to when we are eating.”

So how does this research translate to us humans? Does it mean that your average nine-to-five office worker is better protected from the sun than shift workers, night owls and anyone else who finds themselves eating primarily in the wee hours?

“It is likely that if you have a normal eating schedule, then you will be better protected from UV during the daytime,” said Dr Takahashi. “If you have an abnormal eating schedule, that could cause a harmful shift in your skin clock, like it did in the mouse.”

Dr Bogi Andersen, co-leader of the study from UC Irvine, was less confident, saying more research is needed to better understand the links between eating patterns and UV damage in people — particularly how XPA cycles are affected. He did admit, however, that it was “fascinating … that the skin would be sensitive to the timing of food intake”.

This is not the first study of circadian rhythm Dr Takahashi has been involved in this year — back in July, his research helped reinforce the idea that the time of day food is eaten is more critical to weight loss than the amount of calories ingested.

Published in the journal Cell Metabolism, the study found that mice on a reduced-calorie plan that ate only during their normal feeding cycle were the only ones among five groups to lose weight, despite consuming the same amount as another group fed during daylight. Meanwhile, two groups of mice that were fed at the wrong times during their normal light-dark cycle — those with a 30% calorie reduction and others with unlimited food access during the day — remained active at night, suggesting they had chronic sleep deprivation.

“Translated into human behaviour, these studies suggest that dieting will only be effective if calories are consumed during the daytime, when we are awake and active,” said Dr Takahashi. “They further suggest that eating at the wrong time at night will not lead to weight loss, even when dieting.”

So, next time you find yourself up late watching Netflix and tempted by the prospect of a midnight snack, you might want to consider calling it a night. Not only will you have a better chance of losing weight, you’ll also be protecting yourself from sunburn, skin ageing and skin cancer.