Latitude affects sleep-wake cycle

Studies performed at the Instituto do Sono (CEPID-FAPESP) reveal that people living near the Equator tend to wake and sleep at earlier times.

By Karina Toledo

Agência FAPESP – The difficulty that some people experience in waking up early may not be a simple question of laziness but rather a combination of genetic and environmental factors, including the geographic region in which they live. These are the results of studies conducted at the Instituto do Sono (Sleep Institute), one of FAPESP’s Research, Innovation and Dissemination Centers.

“People who live near the Equator have a greater tendency to be early risers and to sleep earlier. Closer to the poles, individuals become more vespertine (rising later and going to sleep later),” said Mario Pedrazzoli, professor in the Universidade de São Paulo (USP) School of Arts, Sciences and Humanities.

The data, which are being submitted for publication, were presented at the 27th Annual Meeting of the Brazilian Federation of Societies for Experimental Biology (FeSBE), held in Águas de Lindoia on August 2012.

Pedrazzoli says the hypothesis that latitude may be one of the regulating elements in the sleep-wake cycle was proposed in 2005. His team had just published the results of a FAPESP-funded study in the journal SLEEP showing an association between a certain variation in the PER3 gene and delayed sleep-phase syndrome.

“People with that disorder feel sleepiness much later than most people, around four or five o’clock in the morning. This tendency can be problematic for those needing to wake up early,” said Pedrazzoli.

Based on sample studies, the researchers calculated that the allelic variation in homozygosis of the PER3 gene associated with the sleep disorder is present in approximately 10% of individuals, but only a small portion of that group actually develops the syndrome.

“This finding suggests that part of the problem is genetic and part is environmental. We then began to suspect that the person’s geographic location could influence the sleep rhythm,” said Pedrazzoli.

To test the hypothesis, the researchers interviewed 16,000 people throughout Brazil via an on-line questionnaire between 2005 and 2007. The study was funded by the CNPq (the National Council for Scientific and Technological Development).

The questionnaire sought to investigate the times at which people preferred to eat, work, exercise, sleep and wake up. Each answer had a value, and the final sum indicated whether the person was a morning, night or intermediate person.

The scientists based their interpretation of the results on the theory that the change between periods of daylight and dark regulates an organism’s physiological processes, such as sleep and appetite. “According to this theory, the earlier an individual gets a light signal in the morning, the earlier he will feel sleepy,” explained Pedrazzoli.

But the time of sunrise in each city wasn’t the only factor that influenced the study’s results. “Near the Equator, there are approximately 12 hours of daylight all year long. But the higher the latitude, the greater the variation in the number of daylight hours. We noticed that this was the variable making the difference,” he explained.

This finding means, for example, that although the sun rises at nearly the same time in Natal and Porto Alegre in summer, sunset occurs later in the South, causing the people who live there to stay awake longer.

But in the winter, the sun sets at nearly the same time in the North and South of Brazil, whereas it rises earlier in Natal than in Porto Alegre, causing the Northerners to wake and sleep at an earlier hour than those in the South.

Today, Pedrazzoli is coordinating a new research project financed by FAPESP. The project aims to investigate the genotype of population samples from the cities of Natal, São Paulo and Porto Alegre.
“We want to study the variations in the PER3 gene and the sleep patterns of these populations throughout the year in the months with both shorter and longer days,” he said.

Interactions

The PER3 gene is responsible for producing a protein that helps regulate the times of day in which people are more active or less active. Perazzoli says that the occurrence of variations in this gene was first described in 2001.

“We were intrigued because the region of the gene where this variation was found didn’t exist in other mammals normally used in laboratory testing. We suspected that it might only be present in humans,” he said.

But the doctoral studies of Flavia Cal Sabino, done at the Universidade Federal de São Paulo (Unifesp) under Pedrazzoli’s direction with FAPESP funding, investigated many species of monkeys, showing that this region of the genome exists only in primate species.

“All mammals have the PER3 gene, but it appears that an extra piece was inserted in the genome of primates in the course of evolution. Strangely enough, primates are diurnal, whereas most mammals have nocturnal habits,” said Pedrazzoli.

In another doctoral research project directed by Pedrazzoli, Danyella Silva Pereira of Unifesp silenced the PER3 gene in mice to measure its impact on the animals’ sleep behavior.

“Now we’re working with genetically modified animals. The idea is to insert this piece of the gene found only in primates into the mice and mimic the variation between short and long days in the laboratory to better understand the interaction between PER3 and sleep behavior,” said Pedrazzoli.

In his opinion, this knowledge could be useful for preventive medicine. “If we manage to identify a genotype with a greater propensity for sleep disturbances, doctors could orient these people to change their habits or avoid activities that could favor the disease, such as working nights,” he said.