Clusterin/apolipoprotein J is a novel biomarker of cellular senescence that does not affect the proliferative capacity of human diploid fibroblasts

FEBS Lett. 2001 Dec 7;509(2):287-97. doi: 10.1016/s0014-5793(01)03150-7.


Normal human fibroblasts have a limited replicative potential in culture and eventually reach a state of irreversible growth arrest, termed senescence. In a previous study aiming to identify genes that are differentially regulated during cellular senescence we have cloned clusterin/apolipoprotein J (Apo J), a 80 kDa secreted glycoprotein. In the current report we pursue our studies and show that senescence of human diploid fibroblasts is accompanied by up-regulation of both Apo J mRNA and protein levels, but with no altered biogenesis, binding partner profile or intracellular distribution of the two Apo J forms detected. To analyze the causal relationship between senescence and Apo J protein accumulation, we stably overexpressed the Apo J gene in primary as well as in SV40 T antigen-immortalized human fibroblasts and we showed no alteration of the proliferative capacity of the transduced cells. Despite previous reports on tumor-derived cell lines, overexpression of Apo J in human fibroblasts did not provide protection against apoptosis or growth arrest induced by hydrogen peroxide. Overall, our results suggest that Apo J overexpression does not induce senescence but it is rather a secondary consequence of the senescence phenotype. To our knowledge this is the first report that provides a functional analysis of human Apo J during replicative senescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Differentiation / biosynthesis
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / isolation & purification*
  • Cellular Senescence / physiology*
  • Clusterin
  • Diploidy
  • Fibroblasts / cytology
  • Fibroblasts / physiology*
  • Glycoproteins / biosynthesis
  • Glycoproteins / genetics
  • Glycoproteins / isolation & purification*
  • Humans
  • Molecular Chaperones / biosynthesis
  • Molecular Chaperones / genetics
  • Molecular Chaperones / isolation & purification*
  • Oxidative Stress / physiology
  • Recombinant Proteins / biosynthesis
  • Up-Regulation


  • Antigens, Differentiation
  • CLU protein, human
  • Clusterin
  • Glycoproteins
  • Molecular Chaperones
  • Recombinant Proteins