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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

Arantza Infante1, Andrea Gago1, Garbiñe Ruiz de Eguino1, Teresa Calvo-Fernández3, Vanessa Gómez-Vallejo4, Jordi Llop4, Karin Schlangen2, Ane Fullaondo2, Ana M. Aransay2, Abraham Martín3, Clara I. Rodríguez1
  • 1Stem Cells and Cell Therapy Laboratory, BioCruces Health Research Institute, Cruces University Hospital, Barakaldo 48903, Spain
  • 2Genome Analysis Platform, CIC bioGUNE & CIBERehd, 48160 Derio, Spain
  • 3Molecular Imaging Unit, CIC biomaGUNE, Paseo Miramón 182 C, 20009, Donostia-San Sebastian, Spain
  • 4Radiochemistry Department, Molecular Imaging Unit, CICbiomaGUNE, Paseo Miramón 182 C, 20009, Donostia-San Sebastian, Spain
Received: January 23, 2014Accepted: April 3, 2014Published: April 6, 2014
https://doi.org/10.18632/aging.100651

Copyright: © 2014 Infante et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.