Dietary caloric restriction (CR) is the only intervention demonstrated through extensive experimentation to extend the lifespan of a variety of animals with short lifespans. Whether CR can also extend the life of humans remains unanswered. The National Institutes of Aging Caloric Restriction Study maintains long-term colonies of nonhuman primates which provide the best available model to address this question. As part of this unique resource, rhesus and squirrel monkeys, including age-matched groups maintained long term (15+ years) on 30% caloric restricted or ad libitum (AL) diets, are evaluated for many health parameters and markers of aging. However, there has been no in-depth study of ocular aging in these monkeys. Because of its accessibility to non-invasive monitoring, the eye is an ideal organ to evaluate longitudinally whether CR can retard the occurrence of aging and age-related disease. Observations in rats suggest that CR delays age-related changes in the lens and retina by reducing oxidative stress. Since some of the beneficial effects of CR reported in aging rodents have also been observed in aging monkeys such as reduced oxidative stress in skeletal muscle, we hypothesize that CR will reduce oxidative stress and delay aging and age-related disease in the eye. There are two major goals to our project: 1) To determine by comprehensive clinical examinations whether CR retards the development of aging and age related ocular disease (macular degeneration, cataract, glaucoma, optic nerve atrophy) in these monkeys. 2) To confirm and support the clinical observations by histological studies of the ocular tissue using markers of age-related degeneration and oxidative stress, comparing tissues from CR with those from AL monkeys. This research can provide new insights into the cause and possible treatment of human age-related ocular disorders. Because many of these primates are near the end of their lifespan, there is an element of urgency in our goal to correlate noninvasive clinical testing prior with post mortem histology. ? ?
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| Escher, Pascal; Gouras, Peter; Roduit, Raphaël et al. (2009) Mutations in NR2E3 can cause dominant or recessive retinal degenerations in the same family. Hum Mutat 30:342-51 |
