Cardiac aging leads to increased susceptibility to cardiovascular diseases due to compromised structure and function of the heart. Aging is characterized by a series of complex physiological, cellular, and molecular changes. Cellular senescence, a hallmark of aging, is attributed to stable and permanent cell cycle arrest by several molecular activation mechanisms. Growing evidence indicates that cellular senescence plays an important role in the pathophysiology of age-associated cardiac diseases, which is often related to the accumulation of senescent cells within the heart due to aging. Several factors such as epigenetic dysregulation, cell cycle dysregulation, and increased DNA damage are the changes observed in the cells that lead to senescence physiological processes. Increasing evidence suggests that epigenetic-regulating genes have a significant role in cellular senescence-activating pathways. B cell-specific Moloney murine leukemia virus integration site 1(BMI-1) is an epigenetic regulator that has been associated with biological processes including proliferation, development, and differentiation. However, the effect of BMI1 as a regulator of cardiac structure and function remains to be understood. This study explores the role of BMI1 expression in the heart during aging, in validating cellular senescence. Also, the role of BMI1 expression in the heart in regard to promoting premature senescence in an aging heart with and without cardiac injury. BMI1 expression levels in heart cells from aged global Bmi1 mice models are measured using Real-Time Quantitative Polymerase Chain Reaction (RT- qPCR) and western blotting. We hypothesize that the involvement of epigenetic regulation genes such as BMI1 are necessary in mediating cellular senescence during aging. In addition, the loss of BMI1 expression is shown to induce the senescence-activating pathway promoting premature senescence in cardiac aging. Taken together, these studies suggest that epigenetic involving signaling mechanisms play an important role in cellular senescence during cardiac aging. And it could open promising targets for novel therapeutic avenues during the aging process. / Biomedical Sciences
| Identifer | oai:union.ndltd.org:TEMPLE/oai:scholarshare.temple.edu:20.500.12613/9521 |
| Date | 12 1900 |
| Creators | Asangwe, Ngefor |
| Contributors | Mohsin, Sadia, Estaras, Conchi, Barbe, Mary F., Khan, Mohsin |
| Publisher | Temple University. Libraries |
| Source Sets | Temple University |
| Language | English |
| Detected Language | English |
| Type | Thesis/Dissertation, Text |
| Format | 55 pages |
| Rights | IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available., http://rightsstatements.org/vocab/InC/1.0/ |
| Relation | http://dx.doi.org/10.34944/dspace/9483, Theses and Dissertations |
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