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Thyroid. 2018 May;28(5):656-666. doi: 10.1089/thy.2017.0359. Epub 2018 Apr 23.

Transcriptome Network Analysis Reveals Aging-Related Mitochondrial and Proteasomal Dysfunction and Immune Activation in Human Thyroid.

Author information

1
1 Gong Wu Genomic Medicine Institute, Seoul National University Bundang Hospital , Seongnam, Republic of Korea.
2
2 Department of Biomedical Sciences, Seoul National University Graduate School , Seoul, Republic of Korea.
3
3 Interdisciplinary Program in Bioinformatics, Seoul National University , Seoul, Republic of Korea.
4
4 Department of Internal Medicine, Seoul National University College of Medicine , Seoul, Republic of Korea.
5
5 Department of Surgery, Seoul National University College of Medicine , Seoul, Republic of Korea.
6
6 Department of Internal Medicine, Chungnam National University School of Medicine , Daejeon, Republic of Korea.
7
7 Genomic Institute , Macrogen Inc., Seoul, Republic of Korea.

Abstract

BACKGROUND:

Elucidating aging-related transcriptomic changes in human organs is necessary to understand the aging physiology and mechanisms, but little is known regarding the thyroid gland. We investigated aging-related transcriptomic alterations in the human thyroid gland and characterized the related molecular functions.

METHODS:

Publicly available RNA sequencing data of 322 thyroid tissue samples from the Genotype-Tissue Expression project were analyzed. In addition, our own 64 RNA sequencing data of normal thyroid tissue samples were used as a validation set. To comprehensively evaluate the associations between aging and transcriptomic changes, we performed a weighted gene coexpression network analysis and pathway enrichment analysis. The thyroid differentiation score was then used for further analysis, defining the correlations between thyroid differentiation and aging.

RESULTS:

The most significant aging-related transcriptomic change in thyroid was the downregulation of genes related to the mitochondrial and proteasomal functions (p = 3 × 10-6). Moreover, genes that are associated with immune processes were significantly upregulated with age (p = 3 × 10-4), and all of them overlapped with the upregulated genes in the thyroid glands affected by lymphocytic thyroiditis. Furthermore, these aging-related changes were not significantly different according to sex, but in terms of the thyroid differentiation, females were more susceptible to aging-related changes (p for trend = 0.03).

CONCLUSIONS:

Aging-related transcriptomic changes in the thyroid gland were associated with mitochondrial and proteasomal dysfunction, loss of differentiation, and activation of autoimmune processes. Our results provide clues to better understanding the age-related decline in thyroid function and higher susceptibility to autoimmune thyroid disease.

KEYWORDS:

Genotype-Tissue Expression project; RNA sequencing; aging; autoimmunity; mitochondria; thyroid gland

PMID:
29652618
PMCID:
PMC5952342
DOI:
10.1089/thy.2017.0359
[Indexed for MEDLINE]
Free PMC Article

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