Fight Aging!

Many species of bats depend absolutely upon hearing; without effective echolocation they cannot hunt prey or navigate. It is reasonable to suspect that evolution may have selected for resilience in hearing function in this species, whereas those mammals less dependent on hearing for survival, such as our own species, are stuck with an age-related decline in sensory hair cells of the inner ear and their connections to the brain. Is this the case, however? Someone has to do the legwork to find out. In today's open access paper, researchers pick a bat species and capture specimens in the wild to run epigenetic age and auditory function tests.

As is the case for any comparative biology of aging study, determining that a species is unusually resilient to aging in some way is just the first step on a long road. It is already well known that bats have an unusual metabolism in comparison to other mammals as a result of the energy demands of flight. Many bat species are exceptionally long-lived for their size, resistant to some of the damaging processes of aging. Given a specific finding such as a lack of age-related decline in hearing, researchers must then identify the meaningful biochemical differences in affected cell populations and tissues. That is a slow and expensive proposition. Following that comes the even harder exercise: how does one turn this knowledge into a viable therapy for humans? The field as a whole has yet to come to the point of successfully mining the biochemistry of a resilient species and building a therapy based upon an important identified difference.

Resistance to age-related hearing loss in the echolocating big brown bat (Eptesicus fuscus)

Hearing is essential for echolocating bats that rely extensively on their auditory systems to forage, navigate, and avoid obstacles. The evolution of echolocation in bats has been correlated with adaptations at all levels of auditory processing to enable active acoustic sensing of complex and dynamic environments. Consequently, echolocating species are exposed to intense self-generated sounds. Further, many species form high-density aggregations, where sonar sounds emitted by other individuals may be potentially damaging to the cochlea. The critical role of hearing in the fitness and survival of echolocating bats suggests that the evolution of this active sensing system may have introduced selective pressures to protect the auditory system from damage over a lifetime of exposure to sound.

The aging auditory system in most mammals shows a progressive loss of hearing sensitivity that begins with high-frequency deficits and extends to low frequencies over time. Although the etiology of age-related hearing loss (ARHL) is highly variable, depending on genetic, epigenetic, and environmental factors, its onset is generally correlated with senescent changes to the peripheral structures of the auditory system, including loss of inner and outer hair cells, loss of ribbon synapses and retraction of auditory nerve fibers (i.e., cochlear synaptopathy), and deterioration of the stria vascularis. The molecular mechanisms underlying ARHL are hypothesized to result from inter-related metabolic and physiological changes over the lifespan that lead to the accumulation of reactive oxygen species and increase susceptibility to cellular dysfunction.

We hypothesize that echolocation imposes selective pressures to preserve hearing function across the lifespan, especially in species that require echolocation-based active sensing for prey capture. Although bats are not immune to hearing loss, and indeed, some species appear vulnerable to ARHL, recent evidence indicates that species differences in echolocation behaviors may correlate with differential susceptibility to hearing loss. For example, echolocating bat species have shown evidence for resistance to noise-induced cochlear hair cell damage whereas non-echolocating visually dominant species were susceptible to acoustic overexposure and showed levels of hair cell loss comparable to that observed in mice.

In this study, we used DNA methylation to estimate the ages of wild-caught big brown bats (Eptesicus fuscus) and measured hearing sensitivity in young and aging bats using auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). We found no evidence for hearing deficits in aging bats, demonstrated by comparable thresholds and similar ABR wave and DPOAE amplitudes across age groups. We additionally found no significant histological evidence for cochlear aging, with similar hair cell counts, afferent, and efferent innervation patterns in young and aging bats. Here we demonstrate that big brown bats show minimal evidence for age-related loss of peripheral hearing sensitivity and therefore represent informative models for investigating mechanisms that may preserve hearing function over a long lifetime.