What is neuronal aging? Aging can be defined as a condition where stressors are not counteracted by protective functions leading to a dysregulation in development. In the neuroscience world, it is characterized by losses in neuronal function accompanied by behavioral declines (decreases in motor and cognitive performance) in both humans and animals.
The Spanish surrealist cinematographer,
Luis Buńuel, wrote:
"Memory does indeed make us who we
are. But it is important to remember that memory is more than just what we can
consciously recall . . . In order to be yourself, you have to remember who you
are. Keep in mind though that the memories involved are distributed across many
brain systems, and are not always or even mostly available to you consciously."
Uncontrolled oxidation of fatty acids in the brain is believed to be a causative factor in the development of sensory and cognitive defects in old age. It has been shown that dietary fat modifies learning behavior, and by implication, the functioning of the central nervous system (CNS). The experiments studied variations in the amount, or degree of unsaturation of dietary fat and factors (vitamin E) that can modify lipid peroxidation rates. The findings were significant in showing that learning discrimination was severely impaired and the number of errors increased both with an increase in the amount of dietary fat, and increase in unsaturation of the dietary fat. The amount, or degree of unsaturation did not have a significant effect on mortality. However, it was noted that mortality rates were somewhat higher for the higher percent groups [Harman 1976].
Antioxidants Can Modify Fat Oxidation in the Brain
The addition of vitamin E (20mg of a -tocopherol per 100 gm of finished diet) significantly improved performance in discrimination studies and capacity to deal with the operant situation. The results of these studies are compatible with the possibility that enhancing the level of lipid peroxidation has an adverse effect on the CNS out of proportion to its effect on the body as a whole, as measured by mortality rate. It also suggests that variation in the amount or degree of unsaturation of dietary fat and modifying factors such as high doses of antioxidant nutrients that can modify lipid oxidation rates may contribute to the variability in age of onset of evident degradative CNS changes such as senility above and beyond the variations expected from differences in mortality rates [Harman 1976].
The manner in which increases in the amount, or degree of unsaturation of fat alters CNS function is hypothesized on numerous mechanisms. It appears the brain has a high affinity for highly unsaturated fatty acids, particularly docosahexaenoic acid (22:6 w 3). The brain readily absorbs linolenic acid by coverting it to 22:6 w 3 and then binds it tightly. It is in the synaptic areas of the brain where this special affinity takes place [Marwick 1985; Galli 1973; Heikkila 1919; Quimby 1974]. These are the specific areas in humans where the first adverse changes are found-the formation of neuritic plaque which is characteristic of senile dementia.
The polyunsaturated fats derived from precursors of linolenic and linoleic acids have been found to be important functional components of the photoreceptor cell membrane in the eye. The position and number of unsaturated bonds appears to control the electrical response of the photoreceptor cell membrane. A low-fat, low-cholesterol diet can partially ameliorate senile maculopathy, a degenerative retinal disorder [Haddad 1984]. The "hair cells" of the cochlea, the sound-sensing nerves of the human ear, also require these highly unsaturated fatty acids. Similarly, the olfactory bulb in the human is surrounded by a deep layer of myelinated (highly subject to peroxidation) nerve fibers passing to and from the olfactory tract. Taste is so closely related in experience to olfactory sensibility that in speaking it is customary not to distinguish them from one another. This may explain why so many elderly people report loss of taste.
Zinc deficiency is known to play a role in the loss of taste and odor reception. Zinc helps protect lipids from peroxidation as part of the antioxidant enzyme superoxide dismutase (SOD). So it is entirely likely that the decline in sensory perception associated with aging may be partially die to uncontrolled free-radical damage in the brain related to the relative increase in polyunsaturated fat consumption, and deficiencies in absorption or availability of other essential nutrients in diets of the elderly (Ca, Fe, folic acid, B12, intrinsic factor, vitamin B complex, C, zinc, selenium, vitamin D, lack of dark-green leafy vegetables, fiber, lactose intolerance, achlorohydria, protein deficiency, trace minerals) which are essential factors in internal defenses against damage from "internal radiation."
The above neuronal dysfunction may be mediated in part by the deleterious effect of dietary fat on the glial cells (the supporting structure of the nervous tissue). The rate of peroxidation of serum and vessel wall constituents may be increased, leading to a more rapid development of arteriocapillary fibrosis [Marwick 1985]. Increased lipid peroxidation in the synaptic areas, areas rich in polyunsaturated fatty acids [Galli 1973] (such as 22:5 w 6 and 22:6 w 3) could cause damage in a manner similar to that caused by b -hydroxydopamine [Heikkila 1973], or by the anesthetic halothane [Quimby 1974; Van 1975].
A peroxidative autoimmune attack is thought to initiate the autoxidation of L-Dopa and its metabolic product dopamine to b -hydroxydopamine. Thus reaction further autoxidizes to produce free radicals, hydrogen peroxide and hydroxyl radicals. The resultant damage to dopaminergic nerve cells is likely to be the cause of Parkinsons disease. L-Dopa is the amino acid precursor to the neurotransmitter dopamine and is generally effective in improving the symptoms of Parkinsonism. Liquid Deprenyl (Selegiline), a monoamine oxidase inhibitor, protects brain cell membranes from free radical attacks, such as described above.
Also, the intake of nutritional supplements rich in antioxidants and brain chemical building blocks is vital. Refer to Newsletter 30 -- Antioxidants May Decrease Risk Of Alzheimers Disease.
L--Dopa crosses the blood brain barrier, but dopamine does not. Administration of vitamin B6, which helps convert L-Dopa to dopamine peripherally as well as centrally has been shown to temporarily worsen the symptoms of Parkinsons disease when not enough L-Dopa is available to elevate the dopamine levels in the brain. Interestingly, when L-Dopa is used for its other CNS effects such as stimulation of growth hormone [Click here for information on Human Growth Hormone] release, the precaution against use of vitamin B6 has not been found necessary.
There is some evidence that the antioxidant bromocriptine can facilitate L-Dopa by lowering the usual effective dose to half. This has sometimes been found to result in less long-term degeneration and sometimes seems to lead to repairs of damage to dopaminergic nerve cell layers [Teychenne 1983; Vance 1984]. (It should be noted that bromocriptine is structurally related to Ergoloid Mesylates, which may explain its antioxidant effects.)
Vitamin C has been shown to prevent autoxidation of L-Dopa. Vitamin C is an essential membrane stabilizing agent. The concentration of Vitamin C in cerebrospinal fluid (CSF) is about ten times the concentration in the blood. The interior of each nerve cell contains about ten times the concentrations of vitamin C in the CSF. This is one of the CNSs most important defense mechanisms in protecting highly susceptible, but vitally important polysaturated lipid membranes in the brain, and spinal cord from free-radical destruction [Spector 1977].
Cellular aging and Neuronal Function
Membrane stabilizing agents, such as DMAE, phosphatidylserine, centrophenoxine and PABA, have been experimentally shown to speed up lipofuscin removal from nerve and skin cells. Up to 75 percent of the cell volume in old age may taken up by lipofuscin. It is generally believed by gerontologists that the presence of this material leads to seriously disrupted cell function. Lipofuscin, and other aging pigments contain peroxidized fats, cross-linked breakdown products as well as proteinaceous material. The accumulation of age pigments, lipofuscin, ceroid and amyloid, are normally removed from the cell by natural processes involving liposomal enzymatic action. Due to accelerated aging, however, the rate of removal falls farther and farther behind the rate of accumulation [Nanda 1974; Reichel 1970; Harman 1976; Mann 1974; Nandy 1966].
The incidence of amyloidosis was virtually eliminated with the use of dietary antioxidants in the diet. This was reported by Eddy and Harman at the 4th Annual Meeting of the American Aging Association (September 1974). They demonstrated the inhibiting effect of two different antioxidants in the diet on a specific phenomenon of aging-the formation of amyloid, a constituent of senile plaques (frequently referred to as age pigments). In this report it was stated that casein-induced amyloidosis in mice was reduced from 65% to almost zero by diets containing 0.25% of synthetic antioxidants. Ethoxyquin, a free-radical scavenger, had a somewhat greater effect than vitamin E.)
The skin itself has built in alarms in the form of age or liver spots. These brown forms differ from freckles, birth marks and normal skin pigments which are melanin rather than lipofuscin, etc., and do not fade away. The removal of age spots in the skin, and presumably in the nerve cells, reportedly may achieved over a period of several months to a few years in humans [Spoerri 1974; Nandy 1975]. This may be achieved through the use of at least 300mgs of DMAE or Centrophenoxine per day, plus high doses of other supplement antioxidant nutrients in a medically supervised anti-aging program that substantially reduces the accumulation of peroxidized lipids in these issues.