Impact of Environmental and Epigenetic Changes on Mesenchymal Stem Cells during Aging

Abstract

Many crucial epigenetic changes occur during early skeletal development and throughout life due to aging, disease and are heavily influenced by an individual’s lifestyle. Epigenetics is the study of heritable changes in gene expression as the result of changes in the environment without any mutation in the underlying DNA sequence. The epigenetic profiles of cells are dynamic and mediated by different mechanisms, including histone modifications, non-coding RNA-associated gene silencing and DNA methylation. Given the underlining role of dysfunctional mesenchymal tissues in common age-related skeletal diseases such as osteoporosis and osteoarthritis, investigations into skeletal stem cells or mesenchymal stem cells (MSC) and their functional deregulation during aging has been of great interest and how this is mediated by an evolving epigenetic landscape. The present review describes the recent findings in epigenetic changes of MSCs that effect growth and cell fate determination in the context of aging, diet, exercise and bone-related diseases.

Lysine demethylase 3A promotes chondrogenic differentiation of aged human dental pulp stem cells

“…Mounting evidence has shown that epigenetic regulation, including histone modifications, chromatin remodeling, and DNA methylation, are commonly associated with the MSC aging process and may contribute to MSC senescence-related manifestation. 21 , 22 , 23 For example, histone deacetylases (HDACs) mediate self-renewal of MSCs by balancing polycomb group genes and lysine demethylase 6B (KDM6B) expression. 24 It has been shown that upregulation of miR-155-5p lead to elevated cell senescence, while downregulation of miR-155-5p reduce MSC senescence.…”

Mitochondrial Dysfunction in Endothelial Progenitor Cells: Unraveling Insights from Vascular Endothelial Cells

“…These findings indicate that CVRFs have long term effects on circulating EPCs, or even their stem cell precursors (Figure 4). The underlying mechanisms may include epigenetic changes [261,262] as well as covalent modifications of cell components, i.e., oxidative damage of biomolecules, including proteins and lipids, which may lead to potentially irreversible and adverse consequences [263]. Additionally, oxidative DNA damage can induce either permanent genetic or epigenetic changes [264], that might be passed on daughter cells through cell division.…”

Epigenetic Analysis of the Dopamine Transporter Gene DAT1 with a Focus on Personality Traits in Athletes

“…Inducing profound changes in epigenetics may be an underlying factor of the beneficial effects of exercise. The effects of exercise on total DNA methylation in various tissues, including skeletal muscle, adipose tissue and blood, have been demonstrated in many studies [26][27][28].…”