Maria Teresa Blay Olivé
Esther Rodríguez Gallego
Nutrition and Metabolism
Inflammation and autophagy in the gut: searching for new therapeutic targets in unhealthy ageing
The proces of ageing is a natural event but healthy aging is not allways assured, leading to comorbilities such as cardiovascular disease and obesity. Nowadays, aged populations are a hallmark of developed societies and old people often become sedentary and prone to adopt poor nutritional habits. Therefore, given that obesity in the elderly is a serious concern, the comprehension of the key mechanisms of ageing and age-related diseases has become an essential matter.
During ageing, chronic low-grade inflammation, the so called inflammageing, has been suggested to contribute to ageing derangements, including intestinal functions. In addition, one of recent focus in tackling obesity is the study of intestinal dysfunction due to, according to animal and human studies, obesity is characterized by altered gut microbiota, inflammation and gut barrier disruption . However, the specific changes of the inflammatory state along the intestine are still unknown.
A relationship between inflammation, autophagy and the ageing has been pointed out. Numerous studies have highlighted the critical role of autophagy in limiting inflammatory response and in the intestinal homeostasis maintaining intestinal barrier, anti-microbial defence and mucosal response . Moreover, it has been described that malfunctioning autophagy plays an important role in age-related pathophysiology, but the underlying mechanisms are not been fully understood .
In this context, studies on natural food compounds have drawn increasing attention. Our previous studies in rodents indicate that treatments with proanthocyanidins, the most abundant polyphenols in human diet, act as preventives against metabolic distortions induced by an obesogenic diet . These healthy effects are observed on general aspects such as body weight, adiposity but also on intestinal functionality.
Therefore, given this challenging metabolic context, understanding the role of autophagy in intestinal homeostasis, the pathogenesis of inflammation and the possible effects of proanthocyanidins could lead to the development of new strategies in prevention and/or treatment of intestinal diseases.
 Nutr Res Rev. 2016 Dec;29(2):234-248
 J Biomed Sci. 2019 Feb 14;26(1):19.
 Ageing Research Reviews 12 (2013) 237– 252
 Nutrients. 2020 Jan 2;12(1)
2.The objectives of the project, as well as the progress beyond the state-of-the-art.
We hypothesize that plant derived proanthocyanidins, through their interaction with the gastrointestinal tract, could modulate inmune response preventing inflammageing induced by age and obesogenic diets also by modulating authophagy in aged animals and humans. So, the main goal of this proposal is to determine the effectiveness by which proanthocyanidins on the immunoprotective function and autophagy of the gastrointestinal tract by improving the immunecompetence and restoring homeostasis distorted by obesogenic diets and/or ageing.
To achieve it, we will work in the description of the intestinal autophagic status (obese humans and rat models) in different intestinal locations and their relationship with its homeostasis disruption induced by ageing and obesity. On detail, it would be addressed according to the next objectives:
1. To describe the intestinal inflammatory state along ageing in obese patients and in rats with and without an obesogenic diet.
2. To describe the intestinal presence of autophagy and its role in ageing, obesity and its relationship with gut inflammation.
3.To determine the effects of proanthocyanidin treatment on ageing and obesity in relation to their associated gut dysfunction by modulating inflammation and autophagy processes.
4. To understand the whole underlying mechanisms in this metabolic context in order to identify new and more appropriate therapeutic targets in prevention and/or treatment of intestinal diseases.
Ethics: This project involves ethical aspects.
Workplace location: Campus Sescelades, Tarragona
37.5 hours a week
15 March 2021
|This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 945413|