Interaction between epigenetic and metabolism in aging stem cells
Section snippets
Interaction between epigenetic and metabolic pathways in organismal aging
The importance of epigenetic mechanisms in controlling aging has been extensively reviewed [2, 3, 4, 5]. In this section, we will present recent studies that have uncovered intriguing connections between key chromatin regulators and metabolic pathways in the regulation of lifespan in yeast, worms, and flies. These studies help illustrate the importance of the interactions between chromatin and metabolism in the regulation of processes that may be important in cell and tissue aging. For example,
Epigenetics and stem cell aging
Epigenetic changes associated with somatic stem cell aging have been reported for multiple stem cell populations, notably hematopoietic stem cells (HSCs) and muscle stem cells (MuSCs)/satellite cells [19, 20]. In both HSCs and MuSCs, there is an age-dependent increase in the repressive histone modification H3K27me3, whereas H3K4me3, a mark associated with active genes, shows increase in breadth in HSCs but decreases slightly in intensity in quiescent MuSCs with age. In each case, the increase
Direct modulation of epigenetic regulator activity by metabolites in stem cells
While epigenetic states are clearly under multiple levels of control, their direct regulation by metabolites in a variety of cell types, including stem cells, is an area that has recently been of great interest. It is noteworthy that the co-factors important for enzymes that regulate chromatin modifications (e.g., DNA methylation/demethylation, histone acetylation/deacetylation, and histone methylation/demethylation) are metabolites whose levels are determined by the metabolic status of the
Indirect regulation of stem cell function by metabolism: effects of nutrient sensing pathways
While some key regulators of lifespan and healthspan, such as sirtuins, are directly regulated by metabolites, other crucial regulators, including the insulin-FOXO and the mTOR signaling pathways, are global integrators of cellular nutrient and metabolic status (Figure 3). The role of these pathways in the control of stem cell fate has been extensively reviewed [39]. Here, we will focus in how these pathways affect stem cell function and their changes with age, at least in part through
The role of external stimuli: effects of starvation/refeeding and high fat diets on stem cell function
The impact of metabolism on stem cell aging is suggested by the profound effect that caloric restriction has in extending lifespan. In addition, caloric excess (e.g., high fat diets) often has negative healthspan and lifespan effects [51]. Dietary changes that mimic fasting and that delay the onset of age-related pathologies are able to enhance the function of stem cells in multiple tissues [52••]. Prolonged fasting itself promotes HSC-based regeneration of the hematopoietic system [53].
Conclusion and future outlook
While exciting progress has been made in understanding how metabolic process and chromatin modifiers interact in stem cells, it is still unclear how this interaction affects stem cell function, how it is impacted by environmental stimuli, and how it changes during aging. A deeper knowledge of the interaction between chromatin regulators and metabolic processes will be critical for understanding stem cell responses to other physiological processes that impact metabolism such as circadian rhythm,
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
We apologize to the authors whose work we could not cite due to space limitation. We thank Bérénice Benayoun for feedback on the manuscript. Supported by P01 AG036695 (A.B. and T.A.R.) and by the Glenn Center for the Biology of Aging (A.B. and T.A.R.).
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