Common cell biologic and biochemical changes in aging and age-related diseases of the eye: Toward new therapeutic approaches to age-related ocular diseases

Authors: WHITCOMB, ELIZABETH - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; SHANG, FU - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; TAYLOR, ALLEN - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY

Submitted to: Investigative Ophthalmology and Visual Science
Publication Type: Literature Review
Publication Acceptance Date: 8/7/2013
Publication Date: 12/13/2013
Citation: Whitcomb, E., Shang, F., Taylor, A. 2013. Common cell biologic and biochemical changes in aging and age-related diseases of the eye: Toward new therapeutic approaches to age-related ocular diseases. Investigative Ophthalmology and Visual Science. 54(14):ORSF31-ORSF36.

Interpretive Summary:

Technical Abstract: Reviews of information about age related macular degeneration (AMD), cataract, and glaucoma make it apparent that while each eye tissue has its own characteristic metabolism, structure and function, there are common perturbations to homeostasis that are associated with age-related dysfunction. The commonalities appeared to be biochemical stresses and their sequelae. Recognition of shared etiologic factors for age-related debilities allows rationalization of comparable risk factor-disease incidence relationships- such as nutritional risk factors for AMD and cataract (as well as cardiovascular disease and diabetes)- and informs about potential new therapeutic avenues, such as proteolysis enhancers. It also maximizes the return on the investment in research effort and costs. For example, drugs or nutrients that protect against AMD may also prove effective against cataract, glaucoma or/and other age-related neurodegenerative debilities. This article summarizes cell biologic and biochemical changes in aging and age-related diseases of the eye. Clearly, this is a larger challenge with a richer literature than can be properly treated in a short review such as this. In this short review we focus on age-related stresses and current and anticipated means to diminish the stress. Recognizing that almost all age-related diseases such as Alzheimer’s and Parkinson’s diseases, cataract, AMD, glaucoma, diabetes and the premature aging diseases, such as progerias, have in common the accumulation of damaged proteins, we select two aspects of age-related biochemical changes that are common to most eye tissues: 1) problems associated with and/or due to damaged proteins that accumulate in retina, lens and cornea and 2) intracellular degradative capacities that usually keep this levels of damaged proteins process in check in early life or when tissues are not stressed, but that may fail upon stress or aging. Accordingly, we offer apologies to investigators whose work we do not cite or can acknowledge only via reviews. The most rapidly growing segment of many societies is the elderly. The prevalence of cataract, AMD and glaucoma accelerate with age. Among those who are 75 years or older they are about 60%, 15%, and 20% of the population, respectively. These estimates almost double for people just 10 years older. Most eye tissues, like most tissues in general, suffer from the accumulation of damaged proteins. Such accumulation appears to involve post-synthetic modifications to proteins and limits on the proteolytic capacities that are normally available to degrade and remove the altered or obsolete proteins before they transform into cytotoxic aggregates. Collectively, we call the sum of synthesis, post synthetic modification, editing and removal of proteins “proteopoise”. Compromises to proteopoise are also thought to be etiologic for many age-related neuropathies and premature aging syndromes. Herein, we work our way from the anterior of the eye, or cornea, through to the lens and on to the posterior segment or retina, recalling common themes of age-related changes and protein quality control.