RT Journal Article SR Electronic T1 Effects of Long-Term Exercise on Age-Related Hearing Loss in Mice JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 11308 OP 11319 DO 10.1523/JNEUROSCI.2493-16.2016 VO 36 IS 44 A1 Han, Chul A1 Ding, Dalian A1 Lopez, Maria-Cecilia A1 Manohar, Senthilvelan A1 Zhang, Yanping A1 Kim, Mi-Jung A1 Park, Hyo-Jin A1 White, Karessa A1 Kim, Yong Hwan A1 Linser, Paul A1 Tanokura, Masaru A1 Leeuwenburgh, Christiaan A1 Baker, Henry V. A1 Salvi, Richard J. A1 Someya, Shinichi YR 2016 UL http://www.jneurosci.org/content/36/44/11308.abstract AB Regular physical exercise reduces the risk for obesity, cardiovascular diseases, and disability and is associated with longer lifespan expectancy (Taylor et al., 2004; Pahor et al., 2014; Anton et al., 2015; Arem et al., 2015). In contrast, decreased physical function is associated with hearing loss among older adults (Li et al., 2013; Chen et al., 2015). Here, we investigated the effects of long-term voluntary wheel running (WR) on age-related hearing loss (AHL) in CBA/CaJ mice, a well established model of AHL (Zheng et al., 1999). WR activity peaked at 6 months of age (12,280 m/d) and gradually decreased over time. At 24 months of age, the average WR distance was 3987 m/d. Twenty-four-month-old runners had less cochlear hair cell and spiral ganglion neuron loss and better auditory brainstem response thresholds at the low and middle frequencies compared with age-matched, non-WR controls. Gene ontology (GO) enrichment analysis of inner ear tissues from 6-month-old controls and runners revealed that WR resulted in a marked enrichment for GO gene sets associated with immune response, inflammatory response, vascular function, and apoptosis. In agreement with these results, there was reduced stria vascularis (SV) atrophy and reduced loss of capillaries in the SV of old runners versus old controls. Given that SV holds numerous capillaries that are essential for transporting oxygen and nutrients into the cochlea, our findings suggest that long-term exercise delays the progression of AHL by reducing age-related loss of strial capillaries associated with inflammation.SIGNIFICANCE STATEMENT Nearly two-thirds of adults aged 70 years or older develop significant age-related hearing loss (AHL), a condition that can lead to social isolation and major communication difficulties. AHL is also associated with decreased physical function among older adults. In the current study, we show that regular exercise slowed AHL and cochlear degeneration significantly in a well established murine model. Our data suggest that regular exercise delays the progression of AHL by reducing age-related loss of strial capillaries associated with inflammation.