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

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.

• Authors: Arantza Infante, Andrea Gago, Garbiñe Ruiz de Eguino, Teresa Calvo-Fernández, Vanessa Gómez-Vallejo, Jordi Llop, Karin Schlangen, Ane Fullaondo, Ana M Aransay, Abraham Martín, Clara I Rodríguez
• Journal: Aging (Aging (Albany NY)) Vol. 6 Issue 4 Pg. 264-80 (Apr 2014) ISSN: 1945-4589 [Electronic] United States
• PMID: 24753226 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, pathology)
• Transcriptome