"Growing old" is the most common cause of hearing loss. Age-related hearing loss 
(ARHL) (presbycusis) first affects the ability to understand speech in 
background noise, even when auditory thresholds in quiet are normal. It has been 
suggested that cochlear denervation ("synaptopathy") is an early contributor to 
age-related auditory decline. In the present work, we characterized age-related 
cochlear synaptic degeneration and hair cell loss in mice with enhanced α9α10 
cholinergic nicotinic receptors gating kinetics ("gain of function" nAChRs). 
These mediate inhibitory olivocochlear feedback through the activation of 
associated calcium-gated potassium channels. Cochlear function was assessed via 
distortion product otoacoustic emissions and auditory brainstem responses. 
Cochlear structure was characterized in immunolabeled organ of Corti whole 
mounts using confocal microscopy to quantify hair cells, auditory neurons, 
presynaptic ribbons, and postsynaptic glutamate receptors. Aged wild-type mice 
had elevated acoustic thresholds and synaptic loss. Afferent synapses were lost 
from inner hair cells throughout the aged cochlea, together with some loss of 
outer hair cells. In contrast, cochlear structure and function were preserved in 
aged mice with gain-of-function nAChRs that provide enhanced olivocochlear 
inhibition, suggesting that efferent feedback is important for long-term 
maintenance of inner ear function. Our work provides evidence that 
olivocochlear-mediated resistance to presbycusis-ARHL occurs via the α9α10 nAChR 
complexes on outer hair cells. Thus, enhancement of the medial olivocochlear 
system could be a viable strategy to prevent age-related hearing loss.