Prelamin A accumulation and stress conditions induce impaired Oct-1 activity and autophagy in prematurely aged human mesenchymal stem cell

Aging (Albany NY). 2014 Apr;6(4):264-80. doi: 10.18632/aging.100651.


Aging, a time-dependent functional decline of biological processes, is the primary risk factor in developing diseases such as cancer, cardiovascular or degenerative diseases. There is a real need to understand the human aging process in order to increase the length of disease-free life, also known as "health span". Accumulation of progerin and prelamin A are the hallmark of a group of premature aging diseases but have also been found during normal cellular aging strongly suggesting similar mechanisms between healthy aging and LMNA-linked progeroid syndromes. How this toxic accumulation contributes to aging (physiological or pathological) remains unclear. Since affected tissues in age-associated disorders and in pathological aging are mainly of mesenchymal origin we propose a model of human aging based on mesenchymal stem cells (hMSCs) which accumulate prelamin A. We demonstrate that prelamin A-accumulating hMSCs have a premature aging phenotype which affects their functional competence in vivo. The combination of prelamin A accumulation and stress conditions enhance the aging phenotype by dysregulating the activity of the octamer binding protein Oct-1This experimental model has been fundamental to identify a new role for Oct-1 in hMSCs aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Aging, Premature / metabolism
  • Animals
  • Autophagy / physiology*
  • Blotting, Western
  • Cells, Cultured
  • Cellular Senescence / physiology*
  • Fluorescent Antibody Technique
  • Heterografts
  • Humans
  • Lamin Type A
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, SCID
  • Nuclear Proteins / metabolism*
  • Octamer Transcription Factor-1 / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Protein Precursors / metabolism*
  • Reactive Oxygen Species / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Telomere / metabolism
  • Telomere / pathology
  • Transcriptome


  • Lamin Type A
  • Nuclear Proteins
  • Octamer Transcription Factor-1
  • Protein Precursors
  • Reactive Oxygen Species
  • prelamin A