Project Summary/Abstract While there is abundant evidence that certain musical behaviors (e.g., regularly listening to loud music) are risk factors for age-related hearing loss (ARHL), human musicality also has the potential to support hearing health across the lifespan. For example, studies in small samples of younger adults show that individual differences in musical aptitude are positively associated with hearing outcomes such as speech recognition in noisy conditions, and that musicians show enhanced hearing outcomes and auditory processing compared to non- musicians. Further, advances in the genetics of musicality show that genes involved in cochlear development are associated with phenotypic variation in musical aptitude. Preliminary studies also show a positive association between music engagement frequency and hearing sensitivity. Given this evidence, could higher degrees of musicality – both aptitude for and engagement with music – be a protective factor against hearing loss as we age? This project systematically tests this novel hypothesis using experimental, epidemiological, and genomic approaches. Aim 1 uses robust experimental approaches to characterize associations between musical aptitude and hearing outcomes in older adults, over and above music engagement (e.g. practice, formal training, listening) and neurocognitive skills (e.g. executive function). Aim 2 uses epidemiological approaches to characterize associations between music engagement frequency and hearing outcomes in large cohorts of middle-aged and older adults. Aim 3 uses computational genomics approaches to investigate shared genetic architecture between human musicality and ARHL, in large cohorts of middle-aged and older adults for whom available health, phenotypic, and genotypic information is known. Evidence for and against our hypotheses will allow us to disentangle three competing theories about the links between human musicality and hearing health, namely that links are either driven by (a) shared genetic and neural architecture underlying both traits, (b) auditory neurocognitive affordances and preferences shaping musicality, (c) or “wear and tear” of sensorineural auditory biology due to cumulative loud music exposure. Taken together, findings from this project will help evaluate musicality as a protective factor against hearing loss as we age, and lay the groundwork for understanding longitudinal and causal relationships between music engagement and hearing health. Further, findings will lay the groundwork for examining specific biological functions (e.g., expression and regulation) of genes linking musicality, sensorineural auditory mechanisms, and hearing outcomes. This work addresses a critical health need: one in three adults aged 70 or older in the United States suffers from hearing loss, with cascading consequences on social isolation, depression, and cognitive decline and dementia. Innovations in personalized prevention and care are sorely needed. Further the work is timely and leverages recent advances in computational genomics and health biobank approaches, and in the genetics of human musicality traits.

Project Narrative The proposed research is relevant to public health because it evaluates the potential of human musicality – a universal and highly variable trait in the general population – as a protective factor against the inevitable rapid decline in hearing health as people age. Findings from this study will establish necessary groundwork for eventually identifying individuals’ risk and resilience profiles for age-related hearing loss based on their musicality – including aptitude, engagement, and genetic predispositions. This project is therefore relevant to the NIH’s mission to gain insights into the nature and behavior of living systems and to apply this knowledge to reduce illness and disability.