PRE2023-Age-associated T cells in Gut-Brain Axis-PID2022-141169OB-100

With the increase in human life expectancy, there is an urgent need to understand the common molecular pathways by which aging results in a progressively higher susceptibility to chronic multimorbidity, disability and frailty. While the importance of chronic inflammation in the development of age-associated diseases has been widely accepted, a causal contribution of immune cell dysfunction to inflammaging, systemic senescence, and aging has only recently been established by our lab (Desdín-Micó et al, Science 2020) and more recently by others (Yousefzadeh et al, Nature, 2021). These findings have opened a new path to investigate the age-associated T cell changes that occur during aging and instruct T cell differentiation towards a pathogenic or an autoaggressive phenotype that contribute to general body deterioration. Gut-To-Brain will address the hypothesis that the time-dependent deterioration of T lymphocytes contributes to gut dysbiosis, leaky gut and cognitive decline. The Gut-To-Brain project proposes to use interdisciplinary approaches to target age-associated T cells for preventing gut dysbiosis, inflammaging and the onset of age-related cognitive decline. Our central goals are: 1) To define the changes that occur in T cells during aging in the gut and the brain; 2) to deeply characterize the molecular and functional pathogenic properties of age- associated T cells subpopulations that preferentially accumulate in the gut and the brain during aging.