Transcriptomic profiling of pericytes isolated from young and aged mouse stria vascularis identified loss of IGF-1 and the mitochondrial carrier SLC25A33 as an upstream driver of cochlear aging. Deficiency of either protein raised mitochondrial ROS, activated TGF-β/Smad2 signaling, and pushed pericytes into a contractile, barrier-disrupting phenotype, while restoring IGF-1 or SLC25A33 preserved blood-labyrinth barrier ultrastructure and partially recovered auditory function.
Key Points
- Aged cochlear pericytes lose IGF-1 and SLC25A33 expression
- Mitochondrial ROS activates TGF-β/Smad2, triggering pericyte phenotypic switching
- Restoring either protein preserved barrier integrity and hearing in mice
Longevity Analysis
Hearing decline is often treated as an inevitable sensory attrition, yet the mechanism here is vascular and metabolic: microvessel support cells lose mitochondrial capacity, generate oxidative signal noise, and reinterpret that noise as a fibrotic instruction. The same pattern — impaired energy production at the capillary wall driving barrier leak — recurs in the brain, kidney, and retina, which positions cochlear function as an early readout of microvascular health rather than an isolated organ problem. Preserving mitochondrial competence and limiting chronic oxidative load in small-vessel beds becomes a plausible upstream lever, with audiometric thresholds serving as an accessible marker of whether that effort is working.
Original published by Wiley Aging Cell, by Rui Xu, Jia Tang, Huan Lin, Qi Li, Yajin Feng, Xiaorong Zhang, Xiaohong Hu, Jiacai Yang, Yuhong Li, Yang Bai .