Figure 1. LSEC senescence throughout animal lifespan. The accumulation of p16High senescent LSECs starts gradually and is characterized by an increased expression of scavenger receptors (SRs) and endocytic activity in middle (1-year) age animals. This increase well-compensates for the loss of clearing functions by hepatocytes potentially due to LSEC defenestration. Later in life, however, the expression of SRs and LSEC endocytic activity are significantly reduced resulting in build up of blood-born macromolecular waste. This in turn contributes negatively to lifespan.