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 Title: RNA synthesis in adult and senescent female Wistar rats Author(s): Park, Garng Hee Doctoral Committee Chair(s): Buetow, Dennis E. Department / Program: Molecular and Integrative Physiology Discipline: Molecular and Integrative Physiology Degree Granting Institution: University of Illinois at Urbana-Champaign Degree: Ph.D. Genre: Dissertation Subject(s): Biology, Molecular Biology, Animal Physiology Abstract: The process of senescence is accompanied by a progressive decrease in the functional capacities of organisms, organs, tissues and cells to maintain homeostasis. RNA synthesis plays an important role in these functional capacities. Therefore, the objectives of this thesis were to determine any senescence-related changes in the process of RNA synthesis.In chapter I, RNA synthesis by nuclei isolated from senescent (22-26-months) and adult (12-months) female Wistar rat livers was investigated and compared. The results indicated that in senescent nuclei there is a decreased rate (25-42%) as well as maximal incorporation (41-54%) of labelled UTP into both rRNA and mRNA. Several molecular parameters were defined that appear to be involved in the decreased RNA-synthesizing capacity of the senescent nuclei compared to adult nuclei. As a whole, a loss in chromatin binding sites for RNA polymerase appears to account for the senescence-related decline in nuclear RNA synthesis.Isolated hepatocytes may more closely mimic in vivo events than do isolated nuclei because hepatocytes can be isolated in a state in which intracellular organization is maintained. Therefore, studies of RNA synthesis with isolated nuclei (chapter I) were extended to a study of RNA synthesis with isolated hepatocytes (chapter II). The synthesis of total RNA,poly(A$\sp+$) -RNA and poly(A$\sp-$) -RNA is decreased by 35%, 49% and 42%, respectively, in hepatocytes isolated from senescent (25-months) female Wistar rats compared to hepatocytes from adult (12-months) rats. Results from transcription run-on assays indicate that an impaired ability to initiate transcription in senescent hepatocytes underlies their decreased ability to synthesize RNA.Results from chapter I and II indicate an senescence-related decrease in RNA synthesis by isolated nuclei, chromatin or hepatocytes. However, the question arises as to what are the effects of senescence on the expression of specific mRNA-coding genes. Thus, the study was extended to investigate IGF-gene expression in the liver, brain and heart of female Wistar rats during the later stages of life, i.e., young adulthood (6-months-old) to senescent (25 months-old) (chapter III). IGF-I mRNA was detected in liver, heart and brain at all ages. The relative level of IGF-ImRNA decreased the most in the liver from young adulthood to senescence while the relative levels in the heart and brain decreased much less. IGF-II mRNA was detected in the brain and heart but not the liver at all ages. The level of IGF-II mRNA decreased only slightly in the brain from young adulthood to senescence. The senescent heart contained about a third of the amount of IGF-II mRNA found in the young adult heart. Results suggest that both IGFs play important roles in the brain and the heart and that IGF-I plays an important role in the liver throughout the lifespan of the rat. Issue Date: 1989 Type: Text Language: English URI: http://hdl.handle.net/2142/22329 Rights Information: Copyright 1989 Park, Garng Hee Date Available in IDEALS: 2011-05-07 Identifier in Online Catalog: AAI9010980 OCLC Identifier: (UMI)AAI9010980
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