AGING, METABOLISM, AND ALZHEIMER-DISEASE - REVIEW AND HYPOTHESES

Relationships are considered among aging, metabolism, and Alzheimer di sease (AD). In particular, after 60 years, human populations show prog ressive age-related trends for increased blood glucose that are concur rent with the accelerating incidence of AD. The accumulation of glycat ed products in the AD brain, such as is also found in peripheral tissu es during diabetes, suggests interactions of AD with age-related chang es in metabolism. A review of 13 recent studies on AD and diabetes sho ws no consensus, although most studies indicate an apparent exclusion of AD and diabetes. We argue that longitudinal studies are needed to e valuate the possibility that an initial. age-related hyperglycemic sta te is reversed by the cachexia and weight loss common to later stages of AD. A review of literature on chronic food restriction in rodents s hows the slowing of some aspects of aging in the nervous system and ge nerally supports interactions of peripheral metabolism with brain agin g. Finally, we discuss aspects of intermediary metabolism that could e nsue hom oxidative damage to enzymes by glycation or oxidative stress which include excess production of ammonia hom the inhibition of gluta mine synthetase and the production of glyceraldehyde-3-phosphate, a gl ycating agent that could contribute to damage in addition to the hyper glycemic trends during aging. (C) 1997 Academic Press