A human experimental model of laminopathy based on adult stem cells establishes the relevance of Oct1 transcription factor in the aging process

Abstract

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.