Aging

The rapid aging that characterizes Down's syndrome is in line with the accumulating evidence that many degenerative diseases are associated with deleterious activated oxygen species reactions. Activated oxygen species can damage genetic material and inactivate membrane-bound enzymes as well as cause lipid peroxidation in cell membranes. Of particular relevance to Down's syndrome is evidence relating to cancer, inflammatory joint disease, diabetes, degenerative vascular disorders, degenerative eye disease, and senile dementia—all reported to have increased prevalence in Down's syndrome.

The gene for copper/zinc superoxide dismutase is on chromosome 21, and copper/zinc superoxide dismutase levels are elevated by 50% in a range of cells of people with Down's syndrome, including erythro-cytes, blood platelets, leucocytes, and fibroblasts. The increase has also been reported in fetal cerebral cortical cells. Although copper/zinc superoxide dis-mutase usually functions as an antioxidant, it seems likely that in Down's syndrome the raised levels lead to oxidative stress. When the increased production of hydrogen peroxide through catalysis of superoxide free radicals is not matched by a sufficient increase in glutathione peroxidase to metabolize the additional hydrogen peroxide to water and oxygen, there is thought to be an increase in highly reactive hydroxyl radicals leading to increased lipid peroxidation.

Fibroblasts derived from people with Down's syndrome show elevated lipid peroxidation, and levels of thiobarbituric reaction products, which indicate the extent of lipid peroxidation, have been reported to be raised in erythrocytes from Down's syndrome subjects compared to controls.

A reported increase in the activity of the hexose monophosphate pathway in Down's syndrome is thought to be a compensatory mechanism to deal with increased hydrogen peroxide, allowing greater production of the reduced form of nicotinamide-adenine-dinucleotide phosphate, thus improving the ability of cells to reduce oxidized glutathione. However, it has been suggested that this shift of glucose utilization from energy production to reducing power may compromise cellular cation pumps.

Among the genes identified on chromosome 21 is that for the ^-amyloid precursor protein. Amyloido-sis is evident in the brain tissue of both patients with Alzheimer's disease and those with Down's syndrome. Studies are investigating the implications of the anomalies in the expression of the ^-amyloid precursor protein and also the effect on cobalamin/ folate metabolism of the gene for the enzyme cystathionine ^-synthase, also on chromosome 21. The overexpression of both these genes is believed to contribute substantially to the development of dementia of the Alzheimer type. Although all people with Down's syndrome have evidence of brain pathology similar to Alzheimer's disease by their early thirties, not all show Alzheimer-like behavior changes as they age.

It may be that an increase in dietary antioxidants could delay the onset of Alzheimer-type symptoms, but more research is required. However, standard dietary recommendations for healthier lifestyles (i.e., eating more fruit and vegetables and including more oily fish in the diet) may have the added potential benefits of increasing antioxidant intake. Unfortunately, these are often the foods least favored by individuals with Down's syndrome.

Low vitamin E levels have been found to be associated with dementia, not only in the elderly but also in those with Down's syndrome. Vitamin E may have a potential therapeutic role in Alzheimerlike neurological changes by protecting the integrity of the muscarinc receptors. Continuing research into the etiology of the Down's syndrome pheno-type is expected to lead to advances in the treatment of both Down's syndrome and Alzheimer's disease.

5 Ways To Get Rid Of The Baby Fat

5 Ways To Get Rid Of The Baby Fat

Many women who have recently given birth are always interested in attempting to lose some of that extra weight that traditionally accompanies having a baby. What many of these women do not entirely realize is the fact that breast-feeding can not only help provide the baby with essential vitamins and nutrients, but can also help in the weight-loss process.

Get My Free Ebook


Post a comment