The Aging Eyes Study: mitochondrial dysfunction as a driver of age-related vision loss - Abstract The aging of the eyes is a phenomenon that many of us take as a given as we age, vision loss and the subsequent impacts on daily life - less physical activity, higher risk of depression, higher risk of falls, more rapid cognitive function decline - considered immutable consequences of the aging process. Age-related vision loss results from myriad pathways but systemic inflammation and oxidative stress may be a common underlying factor. Not everyone will develop eye disease, though most experience vision changes with age. The vital question is: are there ways to distinguish between individuals along the continuum from normal age-related changes to faster deterioration of vision function to overt pathology? Having an indicator of underlying pathological processes that contribute to faster aging of the eyes would have a large impact on screening and vision care as well as identify high risk groups for clinical trials. Mitochondria, which are central to the production of adenosine triphosphate (ATP), to the regulation of bioenergetic processes, and to various signaling pathways, are susceptible to oxidative stress, resulting in loss of efficiency in oxidative phosphorylation. Mitochondrial damage is a major contributor to age-related diseases through cell apoptosis, dysregulated energy production, and inflammation. Mitochondrial function is increasingly thought to be an important indicator of systemic aging, and mitochondrial diseases frequently involve a range of ophthalmic manifestations. We hypothesize that mitochondrial function and genetics may provide a marker of the biological aging of the eyes as well as provide information on susceptibility to pathologic damage leading to disease. Through this project, we will identify the role of mitochondrial function and genetics in the etiology of aging-related eye diseases. We will build a platform and foster existing collaboration to further investigate the role of mitochondrial function in age-related eye diseases. Lastly, this project will generate knowledge for the development of both mitochondrial function-based clinical indicators of age-related vision loss and provide an evidentiary base for potential interventions on modifiable aspects of mitochondrial function that could slow the aging of the eyes to improve vision health.