Reversing thymus involution by targeting long-lived stem cells

Ageing is accompanied by increased incidence of disorders that impair quality of life. It is a multifactorial process characterized by a progressive loss of tissue repairing capacity with increased inflammation, infections, and incidence of cancer, degenerative andchronic disorders. There is a need to target a societal major challenge which is represented by the dramatic increased of people aged over 60 years that will double by 2050 with enormous impact on health systems. Due to the intrinsic systemic nature of the immune system interconnecting all organs in our body, progressive immune senescence plays a major role in these age-associated disorders.The thymus is a primary lymphoid organ that provides immunity against pathogens, cancer and establishes long-term immune memory. Nevertheless, the thymus starts involuting with puberty and continue into adulthood with essentially atrophy in the elderly. Aged thymus has reduced capacity to raise response to vaccination and ability to eliminate self-reacting immune cells, contributing to inflammation, autoimmunity and cancer occurrence. Therefore, there is an urgent need to build a novel approach for development of therapeutics able to reverse thymus atrophy. Reversing thymus involution will increase circulating anti-inflammatory immune cells, process known as immune rejuvenation.

The REVERSE THYME project has the main goal to develop a robust screening platform for identification of novel compounds able to activate long-lived, well characterized human epithelial stem cells to restore thymic stroma function and T cell output in aged or damaged thymus. The know-how developed in the host laboratory and our capacity to study thymic epithelial cells from aged and diseased thymi define our competitive advantage to develop a transformative approach to enhance the function of the thymus in several conditions affecting it throughout life and ageing.