Fight Aging! Newsletter, February 11th 2019

We report that the bone marrow stromal cell senescence is driven by p16INK4a expression. The p16INK4a-expressing senescent stromal cells then feedback to promote AML blast survival and proliferation via the SASP. Importantly, selective elimination of p16INK4a-positive senescent bone marrow stromal cells in vivo improved the survival of mice with leukemia. Next, we find that the leukemia-driven senescent tumor microenvironment is caused by AML induced NOX2-derived superoxide. Finally, using the p16-3MR mouse model we show that by targeting NOX2 we reduced bone marrow stromal cell senescence and consequently reduced AML proliferation. Together, these data identify leukemia generated NOX2 derived superoxide as a driver of pro-tumoral p16INK4a-dependent senescence in bone marrow stromal cells. Our findings reveal the importance of a senescent microenvironment for the pathophysiology of leukemia. These data now open the door to investigate drugs which specifically target the 'benign' senescent cells that surround and support AML. Autophagy is Everywhere in Aging https://www.fightaging.org/archives/2019/02/autophagy-is-everywhere-in-aging/ Researchers who work on autophagy might well feel justified in issuing the claim that the processes of autophagy are involved in near every aspect of aging. Autophagy is cellular housekeeping, the recycling of damaged or unwanted structures and molecules inside the cell. In chaperone-mediated autophagy, very selective c...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs