Abstract
Ischemic heart disease affects a majority of people, especially elderly patients. Recent studies have utilized autologous adult stem/progenitor cells as a treatment option to heal cardiac tissue after myocardial infarction. However, donor cells from aging patients are more likely to be in a senescent stage. Rejuvenation is required to reverse the damage levied by aging and promote a youthful phenotype. This review aims to discuss current strategies that are effective in rejuvenating aging cardiac stem cells and represent novel therapeutic methods to treat the aging heart. Recent literature mainly focuses on three approaches that aim to reverse cardiac aging: genetic modification, pharmaceutical administration, and optimization of extracellular factors. In vitro genetic modification can be used to overexpress or knock down certain genes and allow for reversal of the aging phenotype. Pharmaceutical administration is another approach that allows for manipulation of signaling pathways related to cell proliferation and cell senescence. Since the stem cell niche can contribute to the age-related decline in stem cell function, rejuvenation strategies also include optimization of extracellular factors. Overall, improving the intrinsic properties of aging stem cells as well as the surrounding environment allows these cells to adopt a phenotype similar to their younger counterparts.
Highlights
Cardiovascular disease is the leading cause of mortality in the United States [1], and its risk increases in patients 65 years of age or older [2]
Previous experiments conducted in the heart have explored whether the adult myocardium contains an undifferentiated pool of cells that may participate in cardiac repair [2]
Another pathway that can be subjected to genetic modification and is a paracrine regulator is the NRG1-ERBB4 signaling pathway (Figure 2)
Summary
Cardiovascular disease is the leading cause of mortality in the United States [1], and its risk increases in patients 65 years of age or older [2]. Mitochondrial overproduction of ROS likely contributes to cellular senescence; it leads to the formation of highly reactive products O2 or H2O2, whose accumulation promotes senescence, DNA mutations, inflammation, and cell death pathways [8]. Rejuvenation is required to reverse the damage imposed by aging to restore tissue and organ function and improve longevity. This review is designed to highlight current work in the field of rejuvenation of aging cardiac stem cells. Certain proteins are found to either increase or decrease in expression in aging organisms, suggesting that reversal of this change in expression may rejuvenate older cells to a youthful phenotype. This review focuses mainly on resident/adult mesenchymal stem cells and cardiac stem/progenitor cells
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