Figure 2. LSEC senescence as an endogenous aging clock. Senescent LSECs loose the ability to clear numerous dangerous substances from blood resulting in an age-induced accumulation of macromolecular waste and toxins. This in turn is further exacerbated by increased intestinal permeability, which induces further increase in the level of endogenous toxins. Once the level of clearance drops below the threshold required for survival (“death cross”), the animal dies.