Abstract
In complex organisms, stem cells are key for tissue maintenance and regeneration. Adult stem cells replenish continuously dividing tissues of the epithelial and connective types, whereas in non-growing muscle and nervous tissues, they are mainly activated upon injury or stress. In addition to replacing deteriorated cells, adult stem cells have to prevent their exhaustion by self-renewal. There is mounting evidence that both differentiation and self-renewal are impaired upon aging, leading to tissue degeneration and functional decline. Understanding the molecular pathways that become deregulate in old stem cells is crucial to counteract aging-associated tissue impairment. In this review, we focus on the epigenetic mechanisms governing the transition between quiescent and active states, as well as the decision between self-renewal and differentiation in three different stem cell types, i.e., spermatogonial stem cells, hematopoietic stem cells, and muscle stem cells. We discuss the epigenetic events that channel stem cell fate decisions, how this epigenetic regulation is altered with age, and how this can lead to tissue dysfunction and disease. Finally, we provide short prospects of strategies to preserve stem cell function and thus promote healthy aging.
Highlights
The statement “Every man desires to live long; but no man would be old,” made by the famousIrish writer Jonathan Swift in 1726 at the age of 60 describes in essence the motivation for the nowadays tremendous research efforts on healthy aging
We focus on the epigenetic mechanisms governing the transition between quiescent and active states, as well as the decision between self-renewal and differentiation in three different stem cell types, i.e., spermatogonial stem cells, hematopoietic stem cells, and muscle stem cells
A common theme emerging is that from a cell’s huge epigenetic arsenal, especially DNA methylation regulated by DNA methyltransferases a cell's huge epigenetic arsenal, especially DNA methylation regulated by DNA methyltransferases (DNMTs) and Ten-eleven Translocation (TET) dioxygenases, as well as particular histone modifications (DNMTs) and Ten-eleven Translocation (TET) dioxygenases, as well as particular histone play a central role in stem cell aging
Summary
The statement “Every man desires to live long; but no man would be old,” made by the famous. A common theme emerging is that from a cell’s huge epigenetic arsenal, especially DNA methylation regulated by DNA methyltransferases a cell's huge epigenetic arsenal, especially DNA methylation regulated by DNA methyltransferases (DNMTs) and Ten-eleven Translocation (TET) dioxygenases, as well as particular histone modifications (DNMTs) and Ten-eleven Translocation (TET) dioxygenases, as well as particular histone play a central role in stem cell aging. With regard to these histone modifications, the euchromatic modifications play a central role in stem cell aging.
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