Research Paper Volume 6, Issue 4 pp 264—280
Prelamin A accumulation and stress conditions induce impaired Oct-1 activity and autophagy in prematurely aged human mesenchymal stem cell
- 1 Stem Cells and Cell Therapy Laboratory, BioCruces Health Research Institute, Cruces University Hospital, Barakaldo 48903, Spain
- 2 Genome Analysis Platform, CIC bioGUNE & CIBERehd, 48160 Derio, Spain
- 3 Molecular Imaging Unit, CIC biomaGUNE, Paseo Miramón 182 C, 20009, Donostia-San Sebastian, Spain
- 4 Radiochemistry Department, Molecular Imaging Unit, CICbiomaGUNE, Paseo Miramón 182 C, 20009, Donostia-San Sebastian, Spain
Received: January 23, 2014 Accepted: April 3, 2014 Published: April 6, 2014
https://doi.org/10.18632/aging.100651How to Cite
Abstract
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.