Aging in physiology and disease

Hematopoietic stem and progenitor cells (HSPC) have the potential to self-renew and undergo differentiation, thus serving as a lifelong reservoir for mature blood cells. Aging results from the inability of HSPC to replenish short-lived cells and guarantee tissue homeostasis. Similarly, stress induced by transplantation as well as extensive ex-vivo manipulation of HSPC in gene therapy approaches may accidentally result in reduced clonal output and premature exhaustion of the human graft, with signs of cellular aging. Our research aims at identifying the molecular determinants leading to HSPC dysfunctions during physiological aging and under stress with the final goal to devise hypothesis-driven strategies to “rejuvenate” HSPC for broader and safer gene and cell therapy applications.