Microbiota and aging · Interaction between gut-microbiota and the central stress system in cognitive alterations associated with aging.
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-05-01 → 2018-04-30
- EU contribution
- €185,076
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Interaction between gut-microbiota and the central stress system in cognitive alterations associated with aging.
The proportion of persons over 65 is expected to reach 37% by 2050. At the worldwide level, the proportion of older individuals (those over 65 years of age) will double between 2000 and 2050, increasing the relative number of older decision makers in society, particularly in developed countries. Aging is also the first risk factor for the development of Alzheimer’s disease (AD), a neurodegenerative disease affecting memory and cerebral integrity and for which no treatment exists yet. Therefore, it is crucial for our modern society to better understand the etiology of aging in order to cope with these population demographic changes to come and to develop innovative and efficient therapies against the detrimental outcomes associated with aging such as learning deficit, depression and AD. Aging is known to be associated with changes in the gut microbiota composition and particularity in the gut. This gut-microbiota (GM) has recently been shown to be particularly relevant for cognition, depression as well as aging with, notably the recent discovery of the repercussion of GM composition on the immune system and a general life span extension by colonization of age mice with GM from young mice. Despite those evidences, the exact role and mechanism at play linking GM to memory deficits in aging or AD is not well understood. Our project aims at: - understanding the role and repercussion of age-associated changes in gut microbiota composition on brain functions by performing GM transfer between young and aged mice to understand the repercussion of the age GM on the young mouse carrier cognition and of the potential of the young GM microbiota to ameliorate cognition in the aged mouse carrier. - deciphering the role of the vagus nerve, the parasympathetic nerve that sends proprioceptive information from the gut to the brain, for the detrimental impact of the aged GM on cognition, - performing humanization of young mice with either human GM from young, aged or AD affected human donors to characterize the impact of aged and AD GM on mouse cognition and isolate microbes and derived metabolites with the potential to positively or negatively impact mouse cognition.
Data: CORDIS, © European Union
Project objective
Aging drives cognitive impairment and general health demise increasing the susceptibility to neurodegenerative disorders in healthy individuals. It is also associated with changes in the gut-microbiota and a general increase in the secretion of stress hormones, known to have debilitating effects when sustained. The gut-microbiota has recently emerged has a crucial modulator of cognitive abilities and general health. Nonetheless, the causes and consequences of the gut-microbiota changes seen in aging are currently unknown. In this application, we propose to study the importance of the age-associated gut-microbiota changes on brain functions, by swapping the gut-microbiota from aged mice into young mice and vice-versa. This will allow knowing the contribution of the gut-microbiota in the cognitive decline and depressive state associated with aging. Furthermore, we will test if the increase in stress hormones known to occur during aging are upstream of those age-associated microbiota changes, by testing the involvement of the amygdala to the hypothalamus-adrenal axis in this phenomena. This will be achieved by using a chemo-genetic approach to control the activation of each component of this pathway. This project will provide the first description of the functional repercussions of the age-associated changes in the gut-microbiota composition on learning and memory deficits and depression, and possibly elucidate one of the upstream mechanisms responsible. The outcome of this work will pave the way toward the elaboration of probiotic treatments against the detrimental effect of aging.
Original text from CORDIS.
Participants
- INSTITUT PASTEUR · ParisCoordinatorFrance
Links
Data: CORDIS, © European Union