Aging-accelerated differential production and aggregation of STAT3 protein in neuronal cells and neural stem cells in the male mouse spinal cord.

Abstract

Aging-affected cellular compositions of the spinal cord are diverse and region specific. Age leads to the accumulation of abnormal protein aggregates and dysregulation of proteostasis. Dysregulated proteostasis and protein aggregates result from dysfunction of the ubiquitin-proteasome system (UPS) and autophagy. Understanding the molecular mechanisms of spinal cord aging is essential and important for scientists to discover new therapies for rejuvenation. We found age-related increases in STAT3 and decreases in Tuj1 in aging mouse spinal cords, which was characterized by increased expression of P16. Coaggregation of lysine-48 and lysine-63 ubiquitin with STAT3 was revealed in aging mouse spinal cords. STAT3-ubiquitin aggregates formed via lysine-48 and lysine-63 linkages were increased significantly in the aging spinal cords but not in central canal ependymal cells or neural stem cells in the spinal cord. These results highlight the increase in STAT3 and its region-specific aggregation and ubiquitin-conjugation during spinal cord aging.