Fig. 1.

Aging increases thrombospondin-1 (TSP1) expression and dysregulates its physiological functions. TSP1 is transiently secreted into the extracellular matrix during embryonic development and in response to wounding in adults, but it is efficiently cleared by cell uptake via calreticulin (CRT) and the LDL receptor-related protein receptor (LRP1). Various physiological functions of TSP1 are mediated by its interactions with specific cell surface receptors and by modulating the function of other extracellular matrix proteins and growth factors. Several chronic and acute conditions associated with aging result in increased TSP1 biosynthesis and accumulation in the extracellular matrix, which perturb TSP1 signaling functions mediated by cell surface receptors and increase the activation of latent TGFβ1.