Evaluation of the association of Aging-Related Immune phenotypes (ARIP) with aging outcomes using transcriptomics.
2022-09
Loading...
View/Download File
Persistent link to this item
Statistics
View StatisticsJournal Title
Journal ISSN
Volume Title
Title
Evaluation of the association of Aging-Related Immune phenotypes (ARIP) with aging outcomes using transcriptomics.
Authors
Published Date
2022-09
Publisher
Type
Thesis or Dissertation
Abstract
Individuals with the same chronological age exhibit different degrees of physiological dysfunction. Biomarkers that determine the underlying biological processes of age acceleration in some individuals compared to others will help understand the mechanisms that determine the dysregulation of homeostatic processes. Senescence of the immune system characterized by an aging-related immune phenotype (ARIP) is being increasingly studied as a biological aging phenomenon. In Manuscript 1, we defined an ARIP marker in the Health and Retirement Study (HRS) using T-cell subsets by comparing associations between candidate ARIP markers and existing ARIP markers with multiple age-related phenotypes including multimorbidity (defined using type II diabetes, heart disease, lung disease, stroke, and cancer). We found that CD4+ naïve T (TN) cells and CD4+ naïve (TN) /memory (TM) T cells ratio had the strongest association with the multimorbidity.
In Manuscript 2, we defined an optimal cut-off point for the ARIP marker (CD4+ TN) and aimed to identify gene expression profiles for this ARIP marker in HRS. Two hundred ninety-two genes were differentially expressed with the cut-off and 1482 genes were differentially expressed with the continuous ARIP marker. However, after adjustment for multiple comparisons, there were no statistically enriched biological pathways among the differentially expressed genes.
In Manuscript 3, we aimed to identify gene expression profiles that may mediate the association of ARIP with multimorbidity and mortality. We first assessed genes associated with both ARIP and multimorbidity. We identified 1998 genes associated with multimorbidity and 93 genes commonly associated with four of the individual chronic conditions. Five common genes (AMIGO1, ZSCAN32, KCNK12, KRT73 and MTRNR2L4) were identified between ARIP and multimorbidity which were also associated with mortality. Two of the genes, AMIGO1 and KRT73, partially mediated the association of CD4+ TN cells on mortality.
Overall, this dissertation provides evidence of immune aging markers and certain genes associated with physiological dysregulation which may motivate future work for a comprehensive understanding of aging mechanisms.
Keywords
Description
University of Minnesota Ph.D. dissertation. 2022. Major: Epidemiology. Advisor: Bharat Thyagarajan. 1 computer file (PDF); 137 pages.
Related to
Replaces
License
Collections
Series/Report Number
Funding information
Isbn identifier
Doi identifier
Previously Published Citation
Other identifiers
Suggested citation
Ramasubramanian, Ramya. (2022). Evaluation of the association of Aging-Related Immune phenotypes (ARIP) with aging outcomes using transcriptomics.. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/250033.
Content distributed via the University Digital Conservancy may be subject to additional license and use restrictions applied by the depositor. By using these files, users agree to the Terms of Use. Materials in the UDC may contain content that is disturbing and/or harmful. For more information, please see our statement on harmful content in digital repositories.