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.

Aging is a major concern in developing societies, which are characterized by an escalation in the aged population as well as in the prevalence of many chronic diseases associated with this inevitable biological process. There is a strong desire to delay aging and increase the length of disease-free life. For that purpose there is a need to better understand the human aging process, as the mechanisms that regulate aging remain largely unknown. The adult stem cell reservoir, which not only declines in size with age, but also particularly handicaps those regenerative tissues repopulated by this reservoir of stem cells, deserves special consideration. We have recently reported the characterization of a new stem cell human experimental model, based on posttranslational defects of the LMNA gene expression associated with progeroid syndromes. In this work, we summarize the necessity of developing reliable human experimental models for the study of human stem cell aging, and outline the phenotypes exhibited by this new experimental human aging model due to accumulation of an aberrant LMNA product with detrimental repercussions to in vivo functionality. This in vitro model has been fundamental for the identification of a novel role of a known transcription factor in human stem cell aging, demonstrating the potential of the model as a tool to unravel the molecular mechanisms governing human aging.To cite this article: Infante, et al. A human experimental model of laminopathy based on adult stem cells establishes the relevance of Oct1 transcription factor in the aging process. Stem Cell Transl Invest 2014; 1: e276.

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