Clearance of Senescent Cells by Rejuvenation of the Aged Immune System
Aging is associated with an accumulation of cells in a state of irreversible cell cycle arrest termed ‘senescent cells’. These cells secret many different pro-inflammatory cytokines and chemokines as well as growth factors and proteases which are called in their entirety “senescence-associated secretory phenotype” or SASP. It is assumed that SASP is an important contributing factor or even driver of age-associated diseases. In mouse models, clearance of senescent cells attenuated age-related diseases. It is well established that senescent cells can be eliminated by various components of the immune system. Since the function of the immune system declines with age, this could be at least partially causative for the accumulation of senescent cells in old individuals.
We will now analyze in our transplantation model if the age-related impaired functional integrity of the immune system contributes to the accumulation of senescent cells in aged individuals and results in increased SASP levels. Furthermore, we will determine if rejuvenation of an aged immune system by rejuvenation of aged HSCs will reduce the senescent cell burden and result in reduced SASP levels.