Transcriptome Network Analysis Reveals Aging-Related Mitochondrial and Proteasomal Dysfunction and Immune Activation
Byuri Angela Cho1,2, Seong-Keun Yoo1,3, Young Shin Song4
11 Gong Wu Genomic Medicine Institute, Seoul National University Bundang Hospital , Seongnam, Republic of Korea.
Summary
Aging impacts the thyroid gland by decreasing mitochondrial and proteasomal gene expression and increasing immune-related genes. These transcriptomic changes are linked to thyroid dysfunction and autoimmune disease susceptibility.
Area of Science:
- Genomics
- Aging Research
- Endocrinology
Background:
- Understanding aging's impact on human organs requires transcriptomic analysis, yet the thyroid gland remains understudied.
- This study investigates age-related transcriptomic alterations in the human thyroid gland to characterize associated molecular functions.
Purpose of the Study:
- To elucidate aging-related transcriptomic changes in the human thyroid gland.
- To characterize the molecular functions associated with these age-related transcriptomic alterations.
- To explore the correlation between thyroid differentiation and aging.
Main Methods:
- Analysis of publicly available RNA sequencing data from 322 thyroid tissue samples (Genotype-Tissue Expression project).
- Validation using 64 RNA sequencing data of normal thyroid tissue samples.
- Application of weighted gene coexpression network analysis and pathway enrichment analysis.
- Utilized thyroid differentiation score to define correlations between differentiation and aging.
Main Results:
- Significant downregulation of genes related to mitochondrial and proteasomal functions with age (p=3×10⁻⁶).
- Significant upregulation of immune-process-associated genes with age (p=3×10⁻⁴), overlapping with genes in lymphocytic thyroiditis.
- Aging-related changes were not sex-dependent, but females showed greater susceptibility to these changes concerning thyroid differentiation (p for trend=0.03).
Conclusions:
- Aging-related transcriptomic changes in the thyroid involve mitochondrial and proteasomal dysfunction, reduced differentiation, and immune activation.
- Findings suggest a link between aging, thyroid dysfunction, and increased susceptibility to autoimmune thyroid diseases.
- Provides insights into age-related thyroid decline and autoimmune disease risk.
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