The clock strikes 10:37 as we enter the garden of the National Cancer Research Centre (CNIO). The sun filters through the nearby five towers, symbols of Madrid’s financial centre, as if it were 10:37 on a late summer’s day. Inside the building, employees are bustling about as if it were 10:37 in the morning. The three clocks that govern our lives – the social, the solar and the internal – seem to be synchronised. But here we are studying what happens when all this is thrown into the winds. Can this imbalance make us more vulnerable to diseases such as cancer?

The answer lies frozen in the basement of the CNIO. There, in enormous refrigerated chests, the first collection of biological samples from cabin crew is kept. This group lives in a jet lag A constant that has consequences for their health. “It’s like a hangover, when you’re young you can handle it and recover quickly, but as you get older it becomes more and more difficult,” explains Virginia López del Alcázar, head of professional health at the Spanish Association of Cabin Crew. She, who was also a crew member, explains that the idea that there are higher rates of illness has taken hold among her colleagues, but they don’t have the data to back it up. So she thought that, instead of speculating, it would be better to establish a scientific basis, since only in this way could they obtain labor protection. She contacted the CNIO, and proposed giving them biological samples to study it. Since 2021, twice a year, more than a hundred flight attendants donate blood, saliva, nails, feces and urine, making up a longitudinal collection in which patterns and trends can already begin to be identified. In this way, a scientific advance could lead to a union advance.

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Maria Jesus Artiga She is the acting scientific director of the CNIO biobank. Walking with her through the facilities is impressive. Dozens of containers lined up hold some 50,000 samples from nearly 9,000 donors. “The numbers are dizzying, but this is a small biobank compared to a hospital,” she explains. “It doesn’t matter, ours is a different concept.” When opening the container, the noise is loud and the fog is dense. The samples are kept at -196 degrees and can only be removed with thick gloves and a face shield. “Here we have chosen to have strategic collections, aimed at a specific line of research,” explains the expert. Only in this way can research such as the one they want to present today be guaranteed.

Biologists Alba de Juan and María Casanova-Acebes were the first to take an interest in this collection. Three floors up, in their laboratory, they explain that their idea is to understand the circadian rhythms of healthy and cancerous cells. They want to dissect these biological clocks, to analyse their mechanisms, to understand whether they can be synchronised to minimise the ravages of disease. They also want to see what happens to our immune system when we stop sleeping. “We think that in people with a changed schedule, the number and function of their leukocytes are no longer optimal,” explains de Juan, “that their immune system is altered. Now we have to prove it.”

María Casanova-Acebes, CNIO biologistPablo Monge

Our internal clock sets circadian rhythms, biological changes that follow a 24-hour cycle and make up a kind of cellular work schedule: at mealtime, our cells secrete certain proteins. An internal alarm sounds because it is time to sleep, and others are released. The next day, the immune system wakes up and the number of white blood cells increases, but the number decreases at nightfall. Everything is synchronized with solar rhythms after millennia of evolution and adaptation to the environment. Disarranging our schedules from those set by our body can have consequences for our health, and scientific literature has begun to analyze them.

Long-term night work is associated with a weight gain. Also It has been pointed out how it increases the risk of coronary heart disease. Less proven is its relationship with cancer. The International Agency for Research on Cancer classifies he work that alters rhythms circadian as “probably carcinogenic. This means that there is already “sufficient experimental evidence” in animals, but “limited” in humans. This limited evidence is supported by studies such as that of the University of Huelva, which analysed a group of nurses who had to work shifts. The study pointed out “significant associations between breast cancer and prolonged rotating night shifts”. It also saw a relationship between alterations in certain circadian rhythm markers (such as melatonin), epigenetic markers (such as telomeres) and breast cancer. This analysis pointed out, but did not support: “further research is needed to confirm these indications”, it said. This is what de Juan and Casanova-Acebes propose to do.

Altering our circadian rhythms can make us more vulnerable to diseases, but knowing the rhythms of these can be the key to combating them. Because viruses, bacteria and cancer cells also seem to be governed by a schedule and an internal clock. This is something that all patients have been able to experience firsthand. Fever usually rises after eating or first thing in the morning. Coughing fits are often more violent at night. These seem like anecdotes, but they are clues. “These are data to be collected, researchers have to confirm or refute this observational part through experiments,” confirms Casanova-Acebes. Her colleague elaborates on this idea, pointing out that what they want is to “give a scientific basis to popular wisdom.”

Their study is striking but not unique. In recent years, when talking about health, attention has begun to be paid not only to the what and how but also to the when. “It has been proven that heart attacks occur more frequently in the morning,” explains Casanova-Acebes. “And that is because there is a greater concentration of inflammatory cells and platelets. Therefore, it is better to give a person who has a blood clot the coagulants at night, giving them time to act.” There are studies underway that also investigate whether the time at which cancer treatments are administered may be relevant and the provisional results, although insufficient, seem to suggest that this is the case. The present analysis could explain why. It is still too early to do so, the biologists clarify. They do not believe they will be able to have data until a year and a half from now. But they are optimistic, being able to have a large and sustained collection over time can make the difference with other similar investigations. They are comparing how cells evolve in three groups: one that makes long-distance trips, another that makes medium-distance trips, and a third, a control group, that hardly travels at all.

Alba de Juan, biologist at CNIOPablo Monge

Her work could be applied to people with chronic sleep deprivation, but they wanted to analyse flight attendants and not people with insomnia for a clear reason. “Insomnia has a very complicated case history,” explains de Juan. “It can be caused by damage to the brain or cognitive level and that adds a certain distortion…” What does seem evident is that anxiety causes insomnia and we live in an anxious society, reflects the biologist. This has an impact on circadian rhythms and, in turn, on our health. “With this issue it could happen like it happened years ago with industrial pastries, where studies showed that it was important to take care of our diet. Thanks to analyses like the one we are doing, we will be able to see the importance of maintaining a healthy circadian rhythm. And this means not only being more protected against cancer, but also to fight against any type of disease or infection.”

Circadian rhythms are set by our internal clock, but this is synchronized with the external clock, with the cycles of the sun and the moon. The use and abuse of artificial light, night work, air travel and the jet lag associated with them have distorted this synchronization. In addition, these external factors are joined by other internal ones. According to the Spanish Society of Neurology, more than four million Spaniards suffer from insomnia. All these facts do not serve to explain the appearance of diseases, they are not carcinogenic as is tobacco or alcohol. But different studies indicate that they can compromise not only our mental health but also our physical health. They are affecting our organism in ways that we still do not fully understand. The work of these scientists from the CNIO can help us understand this and make us take measures.

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