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

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.

Thyroid hormone: sex-dependent role in nervous system regulation and disease

“…The thyroid-related medical problems including hypothyroidism and hyperthyroidism are more common in females than males [ 94 ]. Transcriptomics analysis also revealed that aging-related changes in thyroid tissue are more common in females [ 95 ].…”

Signatures of photo-aging and intrinsic aging in skin were revealed by transcriptome network analysis

“…MRPL22 and MRPL52 ). Down-regulation of such genes may represent declined mitochondrial function which is previously reported as one of the signatures of aging across multiple human tissues [ 4 , 6 , 19 ]. To elucidate this phenomenon further, we analyzed mitochondrial DNA (mtDNA) copy number changes as it is closely linked with mitochondrial biogenesis [ 20 ].…”

“…To elucidate this phenomenon further, we analyzed mitochondrial DNA (mtDNA) copy number changes as it is closely linked with mitochondrial biogenesis [ 20 ]. Since mtRNA expression and mtDNA copy number are highly correlated [ 19 , 21 ], we estimated mtDNA copy number using mtRNA expression. As a result, UV induced mtDNA copy number defect was discovered ( Figure 2C , Mann Whitney test P < 0.001).…”

The importance of nutritional factors and dietary management of Hashimoto’s thyroiditis

“…Therefore, it is assumed that there is a relationship between mitochondrial dysfunction and the occurrence of chronic diseases. Although research on the relationship with Hashimoto's disease is still lacking, the study of thyroid cell transcriptome carried out by Cho et al [21] shows that the changes arising from thyroid aging concern the reduction of gene expression associated with mitochondrial and proteasome functions -important in autophagocytic processes [22] -and increased production of proteins associated with autoimmune processes [21]. This is probably one of the reasons why the risk of Hashimoto's development increases with age.…”