Cell-Surface LAMP1 is a Senescence Marker in Aging and Idiopathic Pulmonary Fibrosis

Abstract

The accumulation of senescent cells (SEN) with aging produces a chronic inflammatory state that accelerates age-related diseases. Eliminating SEN has been shown to delay, prevent, and in some cases reverse aging in animal disease models and extend lifespan. There is thus an unmet clinical need to identify and target SEN while sparing healthy cells. Here, we show that the lysosomal membrane protein Lysosomal-Associated Membrane Protein 1 (LAMP1) is a membrane-specific biomarker of cellular senescence. We have validated selective LAMP1 upregulation in SEN in human and mouse cells. Lamp1+ cells express high levels of prototypical senescence markers p16, p21, Glb1, and have low Lmnb1 expression as compared to Lamp1- cells. The percentage of Lamp1+ cells is increased in mice with fibrotic lungs due to bleomycin instillation. Finally, we use a dual antibody-drug conjugate (ADC) strategy to eliminate LAMP1+ senescent cells.