Cellular retinoic acid-binding protein 1, CRABP1, in thyroid gland aging.

Abstract

Aging differentially affects disease risks of various organs¹. The endocrine organs undergo significant changes along aging. Clinical reports showed increased prevalence of thyroid disorders with age, especially hypothyroidism². Primary hypothyroidism includes congenital, autoimmune, and iatrogenic causes, which can occur throughout the lifespan. But those with unknown aetiology increase dramatically (~5 fold) in the elderly (≥75 years old)^3,4. In thyrocytes, accumulated thyroglobulin requires efficient protein folding in the endoplasmic reticulum (ER)^5,6. When ER experiences protein folding defects, it activates the unfolded protein response (UPR), which determines the life-or-death cell fate. The most fundamental mediator in UPR signaling is inositol-requiring enzyme-1 alpha (IRE-1α)⁷. This study reports, for the first time, a highly conserved gene, Cellular retinoic acid binding protein 1 (Crabp1), critical to thyrocyte function in aging. CRABP1 acts by modulating clustering and activation of IRE-1α, thereby reducing thyrocyte ER stress.