Progeroid syndromes: models for stem cell aging?

Abstract

Stem cells are responsible for tissue repair and maintenance and it is assumed that changes observed in the stem cell compartment with age underlie the concomitant decline in tissue function. Studies in murine models have highlighted the importance of intrinsic changes occurring in stem cells with age. They have also drawn the attention to other factors, such as changes in the local or systemic environment as the primary cause of stem cell dysfunction. Whilst knowledge in murine models has been advancing rapidly there has been little translation of these data to human aging. This is most likely due to the difficulties of testing the regenerative capacity of human stem cells in vivo and to substantial differences in the aging phenotype within humans. Here we summarize evidence to show how progeroid syndromes, integrated with other models, can be valuable tools in addressing questions about the role of stem cell aging in human degenerative diseases of older age and the molecular pathways involved.

mTOR-regulated senescence and autophagy during reprogramming of somatic cells to pluripotency: A roadmap from energy metabolism to stem cell renewal and aging

“…This mTOR-regulated senescence and autophagy during reprogramming of somatic cells to pluripotency cells. Although studies in murine models, such as those addressing progeroid syndromes, have emphasized the importance of both intrinsic (cell-autonomous, such as cell senescence) and environmental (non cell-autonomous, such as circulating insulin-like growth factors) changes as primary causes of stem cell dysfunction, [26][27][28][29] there has been little translation of these data to human aging, likely due to the lack of more adequate experimental models. iPSCs are valuable tools that can definitively address the role of stem cell aging in human chronic diseases of older age and the ultimate signaling pathways that are involved.…”