Acyl-CoA-binding protein as a driver of pathological aging

Abstract

The tissue hormone acyl coenzyme A–binding protein (ACBP, encoded by the genediazepam-binding inhibitor, DBI) has been implicated in various facets of pathological aging. Here, we show that ACBP plasma concentrations are elevated in (close- to- ) centenarians (mean ± SD age 99.5 ± 4.5 y) commensurate with their healthdeterioration, correlating with a reduced glomerular filtration rate and a surge insenescence- associated cytokines. ACBP neutralization by means of a monoclonal anti-body (mAb) improved health span in a strain of progeroid mice. In a mouse model ofchronic kidney injury induced by cisplatin, anti-ACBP mAb administration counter-acted both histopathological and functional signs of organ failure. ACBP inhibition alsoprevented the senescence of tubular epithelial cells and glomerular podocytes inducedby cisplatin or doxorubicin, respectively, as measurable by the immunohistochemicaldetection of cyclin-dependent kinase inhibitor 1A (CDKN1A, best known as p21).