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Epigenetic and Pten Regulation of Longevity Pathways Related to Idiopathic Pulmonary Fibrosis and Organismal Aging

Ware, Tierra A
http://rave.ohiolink.edu/etdc/view?acc_num=osu1480598045664191

Abstract Details

2016, Doctor of Philosophy, Ohio State University, Biomedical Sciences.
Understanding the cellular and molecular mechanisms that impact aging is important to improve accelerated aging diseases and promote healthy living in the aging population. Recent genetic studies provide clues on the mechanisms important in aging, specifically stem cell exhaustion, cellular senescence, telomere attrition and protein quality control mechanisms such as autophagy. Aging and some-age related diseases, such as pulmonary fibrosis are linked to these impaired mechanisms. The PTEN/PI3K/Akt/mTOR pathway is evolutionarily implicated and conserved in organismal longevity. In this pathway, PTEN promotes longevity by negatively regulating PI3K, Akt and mTOR activity. PTEN expression is down regulated in age-related diseases, such as cancer and idiopathic pulmonary fibrosis (IPF), resulting in activation of Akt and mTOR. These events promote cellular and organismal aging, which may drive pathogenic aging. In addition to PTEN as an important determinant of cellular longevity, telomerase activity and autophagy are also evolutionarily implicated and conserved in organismal aging. The overall objective of this proposal is to determine the impact of known aging pathways on organismal and lung aging in two parts. First, in Chapter 2, we elucidate how the loss of PTEN in mesenchymal stem cells (MSCs) impacts organismal aging. Second, we interrogate how the upregulation of DNA methyltransferases (DNMTs) target telomerase (Chapter 3) and autophagy genes (Chapter 4) in primary lung fibroblasts and lung tissues from IPF patients of different severity. We further demonstrate that DNMTs are upregulated via TGFß1in vitro (Chapter 5).
Joanna Groden, PhD (Advisor)
Clay Marsh, MD (Advisor)
Peter Mohler, PhD (Committee Member)
Susheela Tridanapani, PhD (Committee Member)
199 p.
Biomedical Research
Pten loss in MSCs; Aging; IPF; Epigenetics; DNMTs; Autophagy; Telomerase

Recommended Citations

Citations

  • Ware, T. A. (2016). Epigenetic and Pten Regulation of Longevity Pathways Related to Idiopathic Pulmonary Fibrosis and Organismal Aging [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1480598045664191

    APA Style (7th edition)

  • Ware, Tierra. Epigenetic and Pten Regulation of Longevity Pathways Related to Idiopathic Pulmonary Fibrosis and Organismal Aging. 2016. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1480598045664191.

    MLA Style (8th edition)

  • Ware, Tierra. "Epigenetic and Pten Regulation of Longevity Pathways Related to Idiopathic Pulmonary Fibrosis and Organismal Aging." Doctoral dissertation, Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1480598045664191

    Chicago Manual of Style (17th edition)

osu1480598045664191
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© 2016, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.