Accumulation of annexin A5 at the nuclear envelope is a biomarker of cellular aging

Abstract

Cellular senescence is a permanent cell cycle arrest induced by short telomeres or oncogenic stress in vitro and in vivo. Because no single of the established biomarkers can reliably identify senescent cells, the application of new ones may aid the diagnosis of aged cells. Here we show that annexin A5 accumulates at the nuclear envelope during replicative and drug-induced cellular senescence in primary human fibroblasts. This new cellular aging phenotype that we have termed SA-ANX5 (senescence-associated accumulation at the nuclear envelope of annexin A5) is as efficient and quantitative as the well-established senescence-associated β-galactosidase activity assay and p21 immunoreactivity. SA-ANX5 is also observed in aged human skin where is exclusively detected in DNA damage foci-positive/Ki-67-negative cells. We also observed that depletion of annexin A5 by siRNA in human fibroblasts accelerates premature senescence through the p38MAP kinase pathway. These observations establish SA-ANX5 as a new biomarker for cellular aging and implicate a functional role for annexin A5 in cellular senescence.