Presbycusis, age-related loss of hearing, occurs gradually in most individuals. Overall, 10 percent of the population suffers from a hearing loss great enough to impair communication and this rate increases to 40 percent in the population older than 65 years of age (1,2). The etiology of the disease remains unknown. However, as in other age-related diseases, histopathological abnormalities can be identified. These abnormalities involve degenerative changes in the cochlea, including the stria vascularis, spiral ganglion cells, inner hair cells and outer hair cells (3,4). An association between cochlear element degeneration and the severity of hearing loss in presbycusis patients has been demonstrated in our laboratory (4).

Mitochondrial Theory of Aging

There are many theories which provide explanations for aging (5). In the present study we will focus on the mitochondrial theory of aging and its applicability to presbycusis. This theory, first proposed by Harman in 1954 (6) as a “free radical theory,” states that reactive oxygen species (ROS) generated throughout the life of an organism damage mitochondrial macromolecules, including proteins, lipids and mtDNA.  Subsequently, Linnane and colleagues proposed that mtDNA mutations accumulate over time and contribute to the aging process (7). For more background information about mtDNA mutations, please click here.

Significance

The work accomplished in our laboratory will significantly advance our understanding of the relationship between mtDNA deletions and the ganglion cell loss observed in presbycusis.  This knowledge may also provide a means to design a rational approach to therapeutic interventions for this disease process through the development of strategies to minimize the accumulation of mtDNA deletions.  Future developments in this field are likely to focus on identifying the functional consequences of specific mtDNA mutations in aged human tissues and the mechanisms involved in clonal expansion.  The results of this investigation may also influence our orientation to the evaluation of other ear diseases in the future.

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