Gut-InflammAge · Age-associated signatures in the composition and pro-inflammatory status of the gut microbiome in humans and mice, and the impact of a periodic fasting intervention to promote healthy aging

Age-associated signatures in the composition and pro-inflammatory status of the gut microbiome in humans and mice, and the impact of a periodic fasting intervention to promote healthy aging

The proportion of Europeans above 65 years of age is predicted to increase extensively until the year 2050. With age our physical performance declines and we get more prone to develop various diseases including metabolic and cardiovascular diseases. Naturally, healthy aging is of large individual and socio-economic interest. The term “inflammaging” describes the hypothesis that many people develop low-grade chronic inflammation with age. Importantly, inflammation is thought to contribute to age-associated diseases. Prevention of chronic inflammation with age could thus be an import measure to promote healthy aging. This explains the scientific interest to find and understand factors that drive age-associated inflammation, and ultimately, to figure out how they can be stopped from doing so. The gut microbiota, the trillions of microbes living in our gut, can both promote and inhibit inflammation. Our immune system directly interacts with the microbes. It needs to strike a balance between allowing a diverse microbial community in the gut and preventing that too many microbes breach the gut barrier and enter our circulation. People with pronounced inflammation in their gut, for example patients with inflammatory bowel disease (IBD), usually have gut microbiota dysbiosis. This means that the composition of their gut microbes differs substantially from the range of compositions found in healthy people. Immunoglobulin A (IgA) is the main antibody used by the immune system to keep gut microbes from breaching the gut barrier, and more microbes are targeted with high levels of IgA in IBD patients than in healthy controls. Microbiota dysbiosis and a high proportion of IgA coated microbes are accordingly markers of intestinal inflammation. The first major objective of the project was to analyse the microbiota compositions of young and aged healthy Danish individuals and to determine the proportions of IgA coated microbes. We wanted to test whether the two biomarkers would reveal signs of increased intestinal inflammation in the aged individuals. Besides establishing references for potential biomarkers of age-associated inflammation, it is important to determine how healthy aging interventions affect these biomarkers. Many suggested healthy aging interventions are based on diets. Permanent calorie restriction, i.e. reduced energy intake without malnutrition, promotes longer healthspans in various species. But it is extremely hard to follow. Periodic fasting schemes aim at providing similar health benefits by combining periods of calorie restriction with periods of unrestricted calorie intake. Periodic fasting resulted in metabolic health benefits in mice. Not surprisingly, human diets such as the 5:2 diet have been promoted. However, the schemes that were tested in mice used severe calorie restriction. Due to their high metabolic rates, the mice often lost ~10% of their weight in each fasting period. The second major objective of the project was to test how a mild periodic fasting scheme - that is more comparable to human periodic fasting - affects metabolic health and the gut microbiota of mice.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз