A large body of data now exists that supports the theory that chromosomal aberrations are related to the development of cancer and to the aging process. A crucial step in the initiation and early development of many cancers is a chromosomal rearrangement, which produces a novel product of a chimeric gene that has the ability to cause uncontrolled cell growth and proliferation. Chromosomal aberrations also increase with age in several species, including humans. Calorie restriction (CR) is one of the most consistent methods for reducing the frequency of age-related diseases such as cancer and extending life span in many short-lived organisms. However, the mechanisms for the anti-aging effects of CR are not yet understood. A study of rhesus monkeys was begun in 1987 to determine if CR is also effective in reducing the frequency of age-related diseases and retarding aging in long-lived animals. The CR monkeys have been maintained for over ten years on a low fat nutritional diet that provides a 30% calorie reduction compared to a control group of ad libitum-fed animals. Because of the greater similarity of nonhuman primates to humans in life span and environmental responses to diet compared with those of rodents, this colony provides an excellent model for the effects of CR in humans. The long range goal of this research is to determine whether CR has effects on the cell cycle and DNA repair that would reduce the frequency of mutations and chromosomal changes that could otherwise overcome senescence checkpoints and allow for uncontrolled growth and cell division leading to cancer and aging. The objective of this proposal is to test the hypothesis that the accumulation of chromosomal aberrations in aging primates is reduced with long-term calorie restriction. The cytogenetic studies proposed here use a unique animal model for determining whether CR protects chromosomal integrity. The results will be essential in identifying potential mechanisms by which CR acts in cancer prevention and delay of the aging process in long-lived species such as the rhesus monkey and humans.
