The role of polyunsaturated fatty acids in restoring the aging neuronal membrane.

In addition to a gradual loss of neurons in various brain regions, major biochemical changes in the brain affect the neuronal membrane that is the "site of action" for many essential functions including long-term potentiation (LTP), learning and memory, sleep, pain threshold, and thermoregulation. Normal physiological functioning includes the transmission of axonal information, regulation of membrane-bound enzymes, control of ionic channels and various receptors. All are highly dependent on membrane fluidity, where rigidity is increased during aging. The significantly higher level of cholesterol in aging neuronal membrane, the slow rate of cholesterol turnover, and the decreased level of total polyunsaturated fatty acids (PUFA) may result from poor passage rate via the blood-brain barrier, or from a decreased rate of incorporation into the membrane, or a decrease in the activities of delta-6 and delta-9 desaturase enzymes. The added oxidative stress, which leads to an increase of free radicals leading to a decrease in membrane fluidity, may respond to a restricted diet, and thereby overcome the damaging effects of the free radicals. A central focus of this review is that a specific ratio of n-3/n-6 PUFA can restore many of these age-related effects. Copyright 2002 Elsevier Science Inc.