Neuromuscular changes in the aging larynx - Project Summary Age-related vocal atrophy (ARVA) affects a substantial portion of the population. ARVA impairs voice, swallowing, and communication, and is associated with social isolation, depression, and reduced quality of life. Vocal fold muscles are thin, bowed, with an incomplete closure during voicing. The underlying reason individuals experience ARVA is not well understood, and current treatments are often ineffective. Moreover, the diagnosis of ARVA is largely subjective and shows overlap with Alzheimer’s disease-related vocal atrophy. Motor evoked response studies are considered the gold-standard test to diagnose many neuromuscular disorders. This electrophysiologic study produces a compound motor action potential (CMAP), which is a summation of muscle fiber action potentials upon electrical stimulation of the motor nerve. The CMAP assesses the integrity of the nerve, neuromuscular junction, and muscle. The candidate has previously used the CMAP to quantify the degree of injury to the recurrent laryngeal nerve (RLN), which is the primary motor nerve to the larynx, in an animal model. The CMAP has been shown to detect acute changes in laryngeal innervation, measure conduction time changes, and quantify the degree of recovery after injury. The candidate has developed a reliable method to perform laryngeal evoked response studies in an aging rat model and human subjects. Pilot data have led to the central hypothesis that there is progressive desynchronization of efferent nerve-muscle signal in the aging larynx. The overall goal of this proposal is to quantify the neuromuscular changes in the aging larynx. The laryngeal evoked response study is the primary outcome measure and will be performed in a rat model (Aim 1) and in human subjects (Aim 2). The rationale for this proposal is that measuring neuromuscular changes in the aging larynx can lead to targeted treatments for this condition. This proposal combines an animal model and human subjects. While the two aims are not dependent on the other, the animal and human studies help to inform one another. The candidate’s primary mentor is David Marcinek, PhD, and he investigates aging muscle physiology and mitochondrial energetics. Jay Rubinstein, MD, PhD and Randal Paniello, MD, PhD are both co-mentors for this proposal. Both Dr. Rubinstein and Dr. Paniello are surgeon-scientists with expertise in computational neurophysiology and laryngeal injury and recovery, respectively. All three mentors have successfully mentored post-doctoral researchers and physician-scientists in career development programs. Local coursework and training programs in neuroscience, cellular biology of aging, instrumental measures of voice production, and biostatistics will allow for the candidate’s ongoing career development. This proposal will provide a strong foundation for independent investigations testing treatments for ARVA.
