Stem Cell Exhaustion

In a lifetime, several insults occur in human tissues and therefore, the regenerative and repair processes play a crucial role maintaining tissue homeostasis. Adult stem cells (rising from embryonic stem cells) provide a reservoir of cells with capacity to generate somatic cell lineages. Adult stem cells are under control of their microenvironment in the tissue and this region responds to injury, diet, exercise, inflammation, and other factors that impact ageing. The microenvironment links intrinsic mechanisms, microenvironment interactions, and communications with cells in surround for the equilibrium of quiescence, proliferation, and regeneration of stem cells. Unlike embryonic stem cells that proliferate actively, the majority of adult stem cells are in quiescent state and are induced to proliferate for regenerative purposes and repair. Unfortunately, due to ageing, the majority of somatic stem cells presents decreased number and/or function which has been correlated with deterioration in tissue function and repair. Stem cells are susceptible to DNA damage during quiescent state which leads to stem cells exhaustion due to accumulation of mutations. Moreover, epigenetic modifications (DNA methylation in specific genes) are also associated to stem cell exhaustion. Hematopoietic stem cells (HSC) have been extensively studied since they are responsible for the replenishment of blood cells (hematopoiesis) and the study of how the age process affects the number and function of HSC can lead to a further understanding of age-related malignancies, age-related changes in the immunity, and possible targets for therapy. To further understand stem cells exhaustion and age-related diseases a new approach named induced pluripotent stem cells (iPSC) has been used. Promising results have been shown with iPSC in age-related macular disease, Alzheimer’s disease, cardiovascular diseases, and cancer.