Age-related loss of hair cells or primary auditory (= spiral ganglion) neurons in the inner ear is the major cause for presbycusis. The loss of spiral ganglion neurons with a relative preservation of hair cells is classified as neural presbycusis. Thus, prevention of neural loss could be an attractive approach to treat presbycusis. As Epo's neuroprotective potential has been shown in many studies we employed mice overexpressing Epo exclusively in neurons (tg21) for determining their hearing ability at an age of 19–21 weeks and again at an age of 43–45 weeks. Using our newly established setup for behavioral audiometry we found that in contrast to 5 months of age, 11 months old tg21 mice had dramatically improved hearing ability compared to their age-matched wild type (wt) littermates. Threshold differences were up to 35 dB and measurements of the highest frequencies (50–80kHz) were possible in aged tg21 but not anymore in old wild type mice. These findings were confirmed by measurements of the auditory brainstem response (ABR). Cochlear histology revealed in aged wt but not tg21 mice dramatically reduced numbers of spiral ganglion neurons mainly in the basal turn, the location of high frequencies. In conclusion, Epo's neuroprotective action effectively suppresses the development of presbycusis.