Single cell analysis of human thyroid reveals the transcriptional signatures of aging.

The thyroid gland plays a critical role in the maintenance of whole body metabolism. However, aging frequently impairs homeostatic maintenance by thyroid hormones due to increased prevalence of subclinical hypothyroidism associated with mitochondrial dysfunction, inflammation, and fibrosis. To understand the specific aging-related changes of endocrine function in thyroid epithelial cells, we performed single-cell RNA sequencing of 54,726 cells derived from pathologically normal thyroid tissues from seven patients who underwent thyroidectomy. Thyroid endocrine epithelial cells were clustered into five distinct subpopulations, and a subset of cells were found to be particularly vulnerable with aging, showing functional deterioration associated with the expression of metallothionein (MT) and MHC class II genes. We further validated that increased expression of MT family genes are highly correlated with thyroid gland aging in bulk RNAseq data sets. This study provides evidence that aging induces specific transcriptomic changes across multiple cell populations in the human thyroid gland.