PAPP-A: a promising therapeutic target for healthy longevity

Cheryl A Conover,Claus Oxvig

doi:10.1111/acel.12564

Abstract

SummaryPregnancy‐associated plasma protein‐A (PAPP‐A) is a proteolytic enzyme that was discovered to increase local insulin‐like growth factor (IGF) availability for receptor activation through cleavage of inhibitory IGF binding proteins (IGFBPs). Reduced IGF signaling has been associated with increased lifespan and healthspan. Therefore, inhibition of PAPP‐A represents a novel approach to indirectly decrease the availability of bioactive IGF. Here, we will review data in support of PAPP‐A as a therapeutic target to promote healthy longevity.

Highlights

plasma protein-A (PAPP-A) was first identified as a placental protein of primates, but no biochemical function was known prior to our discovery in 1999 that PAPP-A is a proteolytic enzyme
We showed that cultured human fibroblasts secrete PAPP-A, and that PAPP-A cleaves IGF binding proteins (IGFBPs)-4 (Lawrence et al, 1999)
Experimental evidence is accumulating that inhibition of PAPP-A has the potential to promote healthy longevity

Summary

Pregnancy-associated plasma protein-A (PAPP-A) is a proteolytic enzyme that was discovered to increase local insulin-like growth factor (IGF) availability for receptor activation through cleavage of inhibitory IGF binding proteins (IGFBPs). Reduced IGF signaling has been associated with increased lifespan and healthspan. Inhibition of PAPP-A represents a novel approach to indirectly decrease the availability of bioactive IGF. We will review data in support of PAPP-A as a therapeutic target to promote healthy longevity.

Introduction

Findings

Conclusion