May 2019 - Inserm Newsroom

Consumption of ultra-processed food and risk of cardiovascular disease

Posted on May 30, 2019November 23, 2022 by Graziella Cara

In an article published May 30, 2019 in the British Medical Journal, researchers from Inserm, Inra, Université Paris 13 and Cnam in the Nutritional Epidemiology Research Team (EREN) report an increased risk of cardiovascular disease in consumers of ultra-processed foods in the NutriNet-Santé cohort.

In recent decades, dietary habits have shifted towards an increased consumption of ultra-processed foods (see boxed text below), which currently account for over half of the total daily energy intake in many western countries. Such foods are often characterized by lower nutritional quality, in addition to the presence of additives, neoformed compounds and substances from packaging and other contact materials.

Recent studies have shown links between the consumption of ultra-processed foods and an increased risk of dyslipidemia, overweight, obesity, and hypertension.

While the Nutritional Epidemiology Research (EREN) team researchers have already observed links between the consumption of such foods and the risk of cancer, mortality, depression symptoms and functional gastrointestinal disorders, no epidemiological studies had up until now investigated the risk of cardiovascular disease. However, this has changed, thanks to the NutriNet-Santé cohort study by the EREN team – and more specifically by epidemiologist and PhD candidate Dr. Bernard Srour, led by Inserm Research Director Dr. Mathilde Touvier, in collaboration with the University of São Paulo in Brazil.

Over 100,000 participants from the French NutriNet-Santé cohort (followed up between 2009 and 2018) were included. On entry into the study, dietary intakes were collected using repeated 24-hour dietary records (on average, 6 per participant), designed to register their usual consumption of 3,300 different foods and drinks. These were categorized by degree of processing using the NOVA classification (see boxed text below).

During the follow-up period, ultra-processed food intake was found to be linked to a higher risk of cardiovascular disease (n = 1409 cases out of the 105,159 participants), particularly coronary heart disease (n = 665 cases), as well as cerebrovascular disease (n = 829 cases).

An absolute increase of 10% in the proportion of ultra-processed foods in the diet (for example, when comparing two individuals with diets consisting of 15% and 25% of ultra-processed foods, respectively) was linked to a 12% increase in the risk of overall cardiovascular disease (13% for coronary heart disease and 11% for cerebrovascular disease).

This observational study in itself does not enable a causal relationship to be established. However, in addition to the prospective design of the study, the results take into account a large number of sociodemographic and lifestyle factors, including age, sex, smoking status, alcohol consumption, educational level, physical activity and weight, metabolic comorbidities and family history. The results obtained also show that the lower overall nutritional quality of ultra-processed foods may not be the only factor involved.

The nutritional guidelines published recently by the French Public Health Agency (2019) recommend limiting the consumption of ultra-processed foods and opting for unprocessed or minimally processed foods. This is in line with the High Committee for Public Health objective of reducing by 20% the consumption of ultra-processed foods in France by 2022.

Definition and examples of ultra-processed foods

Food and drinks are assigned to one of the four groups in the NOVA classification, based on their degree of processing (unprocessed or minimally processed foods, processed culinary ingredients, processed foods, ultra-processed foods). This study focused on the “ultra-processed foods” group, which includes, for example, sugary and artificially-sweetened soft drinks, vegetables preserved with the addition of sauces containing food additives, vegetable nuggets reconstituted with the addition of additives, confectionery and any processed products with the addition of preservatives other than salt (for example, nitrites), as well as food products made mostly or entirely from sugar, oils and fats and other substances not used in culinary preparations, such as hydrogenated oils and modified starches. Industrial processes notably include hydrogenation, hydrolysis, extruding, and pre-processing by frying. Colors, emulsifiers, texturizing agents, non-sugar sweeteners and other additives are often added to these products.

Examples:

– Salted red or white meats are considered “processed foods”, whereas smoked meats and/or with added nitrites and preservatives, such as sausages and ham, are considered “ultra-processed foods”.

– Liquid soups in cartons prepared using just vegetables, herbs and spices are considered “processed foods” whereas dried soup mixes are considered “ultra-processed foods”.

NutriNet-Santé is a public health study coordinated by the Nutritional Epidemiology Research Team (EREN, Inserm U1153 / Inra U1125 / Cnam / Université Paris 13) which, thanks to the commitment and loyalty of over 160,000 participants (known as “Nutrinautes”), advances research into the links between nutrition (diet, physical activity, nutritional status) and health. Launched in 2009, the study has given rise to over 160 international scientific publications. To mark its 10-year anniversary, a call to enroll new participants is being launched so that together we can continue to further research into the relationship between nutrition and health.

By devoting a few minutes per month to answering various online questionnaires relating to diet, physical activity and health, participants contribute to furthering knowledge of the links between diet and health. With this civic gesture, we can each easily participate in research and, in just a few clicks, play a major role in improving the health of all and the wellbeing of future generations. These questionnaires can be found on the secure platform www.etude-nutrinet-sante.fr

Explaining Chronic and Relapsing Eczema

Posted on May 27, 2019November 23, 2022 by Lea Roy

©AdobeStock

Why do eczema patches caused by skin contact with an allergen reappear in the same areas despite having had time to heal? This is what an International Center for Infectiology Research team with members from Inserm, Université Claude Bernard Lyon 1, Ecole Normale Supérieure de Lyon and CNRS were keen to find out. The researchers discovered that not only do the allergens persist in the skin for several weeks but also that they are not alone in doing so. Indeed, immune cells – known as tissue-resident memory T cells – proliferate at the lesion sites and remain there for long periods, reactivating the onset of eczema patches in the event of re-exposure to the allergen. This research, published in The Journal of Allergy and Clinical Immunology, opens up new perspectives when it comes to understanding the mechanism and treatment of allergic contact dermatitis.

Allergic contact dermatitis (ACD) (a type of eczema) is a skin reaction triggered by exposure to allergens. The resulting inflammation of the upper layers of the skin can last for several days, persists for as long as the area remains in contact with the allergen in question and can even become chronic. It manifests as localized skin rashes (eczema patches) accompanied by itching and burning, and reappears if the healed areas are re-exposed to the allergen.

Tissue-resident memory T (TRM) cells are immune cells that persist in peripheral tissues, such as the skin, over the long term. They contribute to the secondary immune response that – while especially rapid and effective against pathogens encountered previously – can cause the exacerbation of some inflammatory diseases, such as ACD. In the eczema patches caused by ACD, a build-up of TRMs is indeed observed.

A research team at the International Center for Infectiology Research (CIRI), with members from Inserm, Université Claude Bernard Lyon 1, Ecole Normale Supérieure de Lyon and CNRS, studied the contribution of TRMs to the severity and chronicity of ACD in mice. They observed that the TRMs proliferate locally in the areas of the skin in contact with the allergen.

When ACD-induced inflammation resorbs, TRMs gradually accumulate in the epidermis and persist there for several weeks.

If the eczema lesion is re-exposed to the allergen – even if it appears to be healed – these cells are then responsible for the appearance of eczema patches.

The team, in its desire to find out why TRMs persist in the skin, observed that the allergens can remain in the epidermis for much longer than was previously thought (at least one month).

This persistence of the allergens in the healed areas could explain the stimulation over several weeks of the proliferation of the TRMs that are specific to them, as well as their persistence in the eczema lesion.

Finally, the researchers observed that the reactivation of the TRMs responsible for the eczema patches was subject to a retro-control enabled by a specific set of inhibitory receptors carried by the TRMs. When re-exposed to a low dose of allergen, these receptors are activated and suppress the activity of the TRMs, thereby preventing an excessive immune reaction.

This research helps to elucidate the role played by the TRMs in the local reappearance of eczema patches. It also shows that the development of therapeutic strategies to prevent the local reactivation of the TRMs through their inhibitory receptors should open up new perspectives in the treatment of ACD.

The Extraordinary Powers of Bacteria Visualized in Real Time

Posted on May 23, 2019November 23, 2022 by Graziella Cara

Drug resistance in bacterial population. Population of drug resistant bacterial cells producing a fluorescent labelled resistance factor, TetA efflux pump (in red), during treatment with tetracycline antibiotic (in green). Cells producing high levels of TetA efflux pump a capable or effective drug efflux and contain very little tetracycline drug. By contrast, cells containing a lot of tetracycline fail to produce TetA efflux pump.©Christian Lesterlin

The global spread of antibiotic resistance is a major public health issue and a priority for international microbiology research. In his paper to be published in the journal Science, Christian Lesterlin, Inserm researcher at Lyon’s “Molecular Microbiology and Structural Biochemistry” laboratory (CNRS/Université Claude Bernard Lyon 1), and his team were able to film the process of antibiotic resistance acquisition in real time, discovering a key but unexpected player in its maintenance and spread within bacterial populations.

This spread of antibiotic resistance is for the most part due to the capacity of bacteria to exchange genetic material through a process known as bacterial conjugation. The systematic sequencing of pathogenic or environmental strains has identified a wide variety of genetic elements that can be transmitted by conjugation and that carry resistance to most – if not all – classes of antibiotics currently used in the clinical setting. However, the process of transferring genetic material from one bacterium to another in vivo, the time needed to acquire this resistance once the new genetic material is received and the effect of antibiotic molecules on this resistance remained unelucidated.

Real-time visualization

The researchers chose to study the acquisition of Escherichia coli resistance to tetracycline, a commonly used antibiotic, by placing a bacterium that is sensitive to tetracycline in the presence of one that is resistant. Previous studies have shown that such resistance involves the ability of the bacterium to expel the antibiotic before it can exert its destructive effect using “efflux pumps” found on its membrane. These specific efflux pumps are able to eject the antimicrobial molecules from the bacteria, thereby conferring on them a certain level of resistance.

In this experiment, the transmission of the DNA from one specific “efflux pump” – the TetA pump – was observed between a resistant bacterium and a sensitive bacterium using fluorescent marking. Thanks to live-cell microscopy, the researchers just had to track the progression of the fluorescence to see how the DNA of the “pump” migrated from one bacterium to another and how it was expressed in the recipient bacterium.

The researchers revealed that in just 1 to 2 hours, the single-stranded DNA fragment of the efflux pump was transformed into double-stranded DNA and then translated into functional protein, thereby conferring the tetracycline resistance on the recipient bacterium.

The transfer of DNA from the donor bacteria (green) to the recipient bacteria (red) is revealed by the appearance of red localization foci. The rapid expression of the newly acquired genes is revealed by the production of green fluorescence in the recipient bacteria.

How is resistance organized in the presence of an antibiotic?

Tetracycline’s mode of action is well-known to scientists: it kills bacteria by binding to their translational machinery, thereby blocking any possibility of producing proteins. Following this line of reasoning, it would be expected that by adding the antibiotic to the previous culture medium, the TetA efflux pump would not be produced and the bacteria would die. However, the researchers observed that, paradoxically, the bacteria were able to survive and efficiently develop resistance, suggesting the implication of another factor essential to the process of acquiring resistance.

The scientists discovered that this phenomenon can be explained by the existence of another efflux pump that is present in virtually all bacteria: AcrAB-TolC. While this generalist pump is less efficient than TetA, it is still able to expel a small amount of antibiotic from the cell, meaning that the bacteria can maintain minimal protein synthesis activity. Therefore, if the bacterium is lucky enough to have received a resistance gene through conjugation, then the TetA pump is produced and the bacteria becomes durably resistant.

This study opens up new avenues in the search for similar mechanisms in bacteria other than E. coli, and for different antibiotics. “We could even consider a therapy combining an antibiotic and a molecule able to inhibit this generalist pump. While it is still too soon to envisage the therapeutic application of such an inhibitor, numerous studies are currently being performed in this area given the possibility of reducing antibiotic resistance and preventing its spread to the various bacterial species” concludes Lesterlin.

The Health of 200 000 Volunteers Tracked by Inserm

Posted on May 23, 2019November 23, 2022 by Graziella Cara

People©Fotolia

Over two-hundred thousand. That is the number of people living in France who have enrolled in Constances since 2012. This unparalleled record makes the cohort the country’s largest epidemiology and public health research project, with few equivalents on the international level.

Performed in partnership with Inserm, the French national health insurance fund, the French national retirement pension fund and the universities of Versailles-Saint-Quentin-en-Yvelines and Paris Descartes, Constances aims to track the long-term health of its volunteers in order to deepen our understanding of the factors that influence it, such as diet, environment or working conditions.

Constances is a research infrastructure that is funded within the framework of the Investments for the Future programs.

Constances represents:

205 000 participants – almost 97% of whom accept to be paired to the databases of the French National System for Health Data
several thousand variables for each individual
80 research and public health projects ongoing
over 190 researchers working on its data in France, Germany, UK, Spain, Finland, Italy, Sweden, Canada, Denmark and the USA
participation in 11 French and international research consortiums
a rapidly growing number of scientific publications

“With the surge in Big Data and Artificial Intelligence, if public research is to inform public decision-making on such sensitive issues as pesticides or mobile telephones, we need powerful and secure research instruments like Constances,” explains Marie Zins, Scientific Director of the cohort.

Constances: a living project

Seven years after the launch of Constances, new projects are being created in order to improve yet further its contributions to research. The collection of biological specimens to form a biobank began at the end of 2018, with almost 95% of the participants approached who gave their consent. In 2019, the volunteers will complete their online ‘’residential calendar’’ with the addresses of everywhere they have ever lived since birth, which will open up immense perspectives for studying the effects of the environment (atmospheric pollution, pesticides, light pollution, etc.) on health. It does not stop there. Constances is also contributing to the French Plan for Genomic Medicine, thanks to the whole genome sequencing of a subsample of participants to constitute a database of genetic variations in our populations.

The cohort’s researchers will present their latest findings at a scientific day held on May 23, in Paris. The topics covered will include work stress and the risk of benzodiazepine misuse, the epidemiology of NASH in France, the use of e-cigarettes and the long-term reduction of smoking, and the link between depressive symptoms and vegetarian diets.

Constances: advancing research to improve health

Link between depressive symptoms and vegetarian diets

While vegetarian and vegan diets (which exclude the consumption of certain animals or any products of animal origin) appear to be generally good for physical health, some studies have reported a link to an increased frequency of depressive symptoms. In just over 90 000 subjects from the Constances cohort, the researchers revealed such a link with pesco-vegetarian diets (which allow the consumption of fish) and lacto-ovo-vegetarian diets (which allow the consumption of eggs and dairy), even when sociodemographic and health-related factors were taken into account. However, this link was not present in frequent consumers of legumes (lentils, chickpeas, soya, etc.) or in those following such diets “for their health”. What is more, this link was not specific to the exclusion of animal products in particular but was observed irrespective of the food group excluded. For example, the increased probability of depression found with a diet low in vegetables was twice as high as that observed with a diet low in meat.

These findings, which cannot affirm a causal relationship, suggest that depression is linked to a tendency to restrict the variety of foods consumed, whatever those foods might be.

Study reference: http://dx.doi.org/10.3390/nu10111695

Benzodiazepines: chronic consumption and work stress

Benzodiazepines are the most prescribed drugs worldwide due to their anxiolytic effects. However, their treatment indications are limited, and it is not recommended to use them for long periods of time due to the risk of dependency and their numerous side effects. The subjects most exposed to these side effects are chronic users. Based on data on treatments dispensed in pharmacies to over 9000 Constances participants enrolled in 2015, the researchers calculated prevalences of chronic benzodiazepine use that were representative of France’s general population. These prevalences were particularly high in that chronic benzodiazepine use concerned 2.8% of men and 3.8% of women in France in 2015. These prevalences rose to 9.3% of men and 12.2% of women in the over-50s age group.

Chronic benzodiazepine use is therefore particularly common in the general French population and the subjects most vulnerable to their side effects are paradoxically those who are the most affected.

In another study, the researchers looked at the links between stress at work, measured using an internationally validated scale, and the risk of chronic benzodiazepine use. Based on a sample of over 30 000 workers enrolled in Constances between 2012 and 2014, with no recent history of chronic benzodiazepine use, the researchers calculated the risk of chronic use over a two-year follow-up period.

They found that stress at work was linked to an increased risk of chronic benzodiazepine use – a risk that increased with the intensity of the stress at work. For the most stressed subjects, the risk of chronic benzodiazepine use was at least two-fold.

Study reference: https://doi.org/10.1186/s12889-019-6933-8

NASH: affects almost 1 in 5 people in France

Metabolic steatosis (“fatty liver”) and more particularly nonalcoholic steatohepatitis (NASH), is an emerging hepatic disease linked to the global epidemics of obesity and diabetes, and likely to lead to liver cirrhosis and cancer. Based on the Constances cohort and with the help of indirect markers, the researchers determined that the prevalence of metabolic steatosis was 18.2% in France’s adult population, including 2.6% with advanced liver disease, that it was twice as common in men than in women, and that it increases with age. There is an inverse relationship with the socio-economic level and a North-to-South gradient.

Obesity and diabetes are major risk factors. Study of the impact of metabolic steatosis and NASH on morbidity-mortality in France’s general population is ongoing.

Are e-cigarettes effective in reducing smoking long-term?

This study involved 5400 smokers and 2025 ex-smokers from the Constances cohort (2012-2016; cessation of smoking from 2010, the year e-cigarettes went on sale in France). In total, 15% of the smokers and around 9% of the ex-smokers reported using e-cigarettes at the time they were interviewed. Over an average 2-year follow-up period, the smokers using e-cigarettes reduced their tobacco consumption more than the non-users (from 4.4 cigarettes/day to 2.7 cigarettes/day). Furthermore, 40% of the e-cigarette users were able to stop smoking during the follow-up period, versus 25% of the smokers who were not using an e-cigarette. However, the ex-smokers who were using e-cigarettes had a higher probability of resuming smoking than those who were not using e-cigarettes (31 vs. 16%).

In conclusion, e-cigarettes enable smokers to cut down on their smoking or to stop smoking altogether, but these effects do not always appear lasting. It is therefore necessary to closely monitor e-cigarette users and advise total tobacco withdrawal to reduce the risk of relapse.

Publication in progress

To find out more about this event: consult the program.

Journalists wishing to attend this event must have prior authorization from the Inserm Press Office rf.mresni@esserp

World multiple sclerosis Day

Posted on May 22, 2019August 17, 2022 by Graziella Cara

Multiple sclerosis ©Inserm/RIEGER F

World MS Day 2019 will take place on 30 May.

The 2019 campaign is called ‘My Invisible MS’ and the theme is visibility.

Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system. It causes the progressive destruction of the myelin sheath surrounding the nerve cells, which is essential for their protection and for the transmission of nerve impulses, leading to motor, sensory, and cognitive disruption.

Inserm teams are mobilized to further research into MS.

At present, magnetic resonance imaging (MRI) is widely used to diagnose and follow up patients with the disease. However, no imaging tools exist to predict the onset of relapse.

Researchers from the “SpPrIng” team, led by Fabian Docagne at Inserm Unit 1237 in Caen, France, have developed an MRI technique in which the progression of the disease can be followed in space and time in a murine model of MS. To do this, they used MRI-detectable iron beads that bind to the adhesion molecules.

The ability to effectively repair myelin is a key factor in countering the progression of MS. Understanding why and how some patients are able to better manage the disease than others is essential.

Read our report (only available in French): “Sclérose en plaques (SEP), Une recherche active pour améliorer la prise en charge des patients”

Read our press release: “MS: using MRI to predict relapse”

Read our press release: “Multiple sclerosis: Mission Regeneration !“

Wound Dressings to Regenerate Joints

Posted on May 14, 2019November 23, 2022 by Graziella Cara

Researchers from Inserm and Université de Strasbourg at Unit 1260 “Regenerative Nanomedicine” have developed an implant which, when applied like a wound dressing, regenerates cartilage in the event of major joint lesions and incipient osteoarthritis. The details of this innovation, which has been validated in the preclinical setting, have been published today in Nature communication.

Increases in life expectancy and the number of accidental traumas call for the development of new types of surgery to replace defective joints. Among the chronic diseases, osteoarthritis – described as destruction of the cartilage affecting the various joint structures, including the bone and synovial tissue that lines the inside of the joints – represents a genuine public health issue. Depending on the clinical diagnosis, various therapeutic options are possible – ranging from microtransplant to joint replacement. Nevertheless, these procedures are all invasive, potentially painful, limited in efficacy and not without side effects. In reality, apart from joint replacement, current treatment strategies are limited to temporary cartilage repair and pain relief. Treatments mainly involve the injection of anti-inflammatories as well as hyaluronic acid to improve joint viscosity. Stem cells can also be used, particularly because they secrete molecules able to control the inflammation.

Within this area and with the aim of regenerating this supple and often elastic connective tissue that covers our joints and enables the bones to move and slide in relation to each other, a team of researchers from Inserm and Université de Strasbourg has recently developed a dressing for cartilage – inspired by the new-generation wound dressings that act as a second skin. With the dressings developed by Ms. Benkirane-Jessel and her team, the therapeutic response reaches a new milestone. We are no longer talking about repair but the actual regeneration of the joint tissue.

What Ms. Benkirane-Jessel’s team has developed is an innovative osteoarticular implant technique, able to reconstitute a damaged joint and whose application can be likened to that of wound dressings. “The implant we’ve developed is intended for two cases in particular: major cartilage lesions and incipient osteoarthritis.” she explains.

These dressings comprise two layers. The first – which acts as a support (reminiscent of everyday wound dressings) – is a membrane comprised of polymer nanofibers and supplied with small vesicles containing growth factors in quantities similar to those secreted by our own cells. The second is a layer of hydrogel loaded with hyaluronic acid and stem cells from the patient’s own bone marrow. It is these cells that – by differentiating into chondrocytes (cells that form the cartilage) – will regenerate the joint cartilage.

The scientists envision a promising future for their “cartilage dressing” which, in addition to the shoulder and knee joints, could also be used for the temporomandibular joint that connects the jawbone to the skull. Quite incapacitating, disorders in this area can cause pain, joint sounds and above all the inability to open and close the jaw completely. The research team has already conducted studies on cartilage lesions in small and large animals (mice, rats, sheep and goats), which are highly suitable models with cartilage comparable with that of humans. The objective is to launch a study in humans with a small cohort of 15 patients.

This project has received the support of Satt Conectus, ANR and the Grand Est region.

Sunday, May 12th: International Fibromyalgia Awareness Day

Posted on May 9, 2019August 17, 2022 by Graziella Cara

26th International Fibromyalgia Awareness Day

Recognized as a rheumatic disease by the WHO in 1992, fibromyalgia is characterized by chronic widespread and persistent pain occurring in multiple areas of the body. This affects functional capacity, which varies over time and from individual to individual.

According to the French National Authority for Health (HAS), between 1.4% and 2.2% of the country’s population are considered to be affected, with 80% of those diagnosed being women.

In addition, sufferers very frequently experience chronic fatigue, cognitive dysfunction, attention and sleep disorders, as well as mood disturbances. These symptoms that are associated with the chronic pain encountered in fibromyalgia can negatively impact daily living activities. Sufferers may find it difficult to hold down a job, for example, or their family or social lives may be affected, which can in turn lead to depression.

In addition to being difficult to diagnose, many attempts have been made to treat fibromyalgia, involving medication and other types of therapy.

A collective expert review by Inserm on fibromyalgia, commissioned by the Direction Générale de la Santé (French Department of Health), is currently being carried out. The results will be published by the end of the year.

Committed to improving the diagnosis of fibromyalgia and the management of the associated chronic pain, the researchers at Inserm are available to answer your questions.

Read more on the subject on the Inserm Press Room :

“A new solution for chronic pain“, published 03/12/2018

Read the article (in French) “Fibromyalgie, l’invisible douleur “, published in Science&Santé (n°35, March-April 2017).

Human “Jumping Genes” Caught in the Act!

Posted on May 2, 2019November 23, 2022 by Graziella Cara

Over the course of evolution, the genomes of most living organisms have grown more complex thanks to transposable elements, a.k.a. “jumping genes,” or DNA fragments that can move and copy themselves from one chromosome location to another. Researchers from Inserm, the CNRS, Université Côte d’Azur, and Université de Montpellier were able to capture these “jumping genes” just after they moved. The researchers compared their observations with existing databases. Their work, to be published in Molecular Cell, shows that the integration of “jumping genes” in humans is not random. Instead, it is thought to be influenced by specific genome properties. These results open up new perspectives for interpreting whole genome sequencing data.

Transposable elements, also known as “jumping genes,” are small DNA fragments that can multiply and move in the chromosomes of most living organisms. They have proliferated so intensely in mammals and primates that they make up more than half of our chromosomes! Of course, they don’t jump all at once in all of our cells. Of all the copies present in our DNA, only a small fraction remain active. All the rest are molecular remnants reflecting millions of years of evolution, during which harmful insertions were eliminated and beneficial ones retained.

In humans, the most active jumping genes are L1 retrotransposons. They can alter or destroy genes when they jump, triggering the manifestation of genetic diseases like hemophilia and muscular dystrophy. L1 retrotransposons are also particularly active in some forms of cancer, and could be involved in cellular aging or in some mental illnesses.

Do L1 retrotransposons target specific chromosome regions, or do they choose their positions at random? Teams led by Inserm head researchers Gaël Cristofari and Simona Saccani working at the Nice Institute for Research on Cancer and Aging (IRCAN, Inserm, CNRS, Université Côte d’Azur), along with their colleagues at Université de Montpellier, were able to use a “high-speed” genome sequencing technique to catch actively jumping genes right after they jumped to a new position.

After comparing their observations with genomic and epigenomic databanks, the researchers were able to identify which genome characteristics influenced the integration of the L1 retrotransposons. The most notable characteristic was DNA replication, and natural selection phenomena after integration played a preponderant role.

“We already knew that L1 retrotransposons tend to accumulate in specific areas of our chromosomes, especially heterochromatin. But we didn’t know whether that reflected a particular attraction to those regions, or if they are simply tolerated in those regions and eliminated elsewhere through natural selection. When we know where they jump to and which copies are retained over the course of evolution, we can discover – by deduction – the regions where they can do damage,” explains Cristofari.

Their results make it easier to understand how jumping genes can trigger mutations in humans, and how they contribute to the evolution of our genetic heritage. In the future, this research could be used to interpret whole genome sequencing data, particularly in personalized medicine and vast sequencing programs.

The research was made possible with financial support from the Fondation pour la Recherche Médicale, Cancéropôle PACA, the European Research Council, the French National Research Agency, the Labex Signalife, the Groupement de Recherche sur les Eléments Transposables (CNRS, GDR 3546), the FHU OncoAge, and the European Erasmus Mundus Mobility with Asia program.

Inserm Newsroom - Press room of the French national institute of health and medical research

Month: May 2019