Down Syndrome

Down syndrome (mongolism) is another example characterized by several symptoms, including accelerated aging and premature death, and is due to trisomy at chromosome 21. The incidence of the syndrome is greatest among children born from mothers 40 years of age and older, and the genetic abnormality has, therefore, been related to aging processes involving the oocytes (Chapter 10). Although in 20% to 30% of cases, the extra chromosome is contributed by the father, paternal age does not seem to have any significant effect on the incidence of the syndrome.

Individuals affected by Down syndrome may present somatic malformations, but the major deficit is represented by severe mental disability. Affected subjects who live to reach 30 years of age and longer present many signs of accelerated aging, including Alzheimer disease (AD) superimposed on the mental retardation (88) (Chapter 7). Animal models have also been proposed for the study of Down syndrome. The mouse is the animal of choice, for it is possible to introduce trisomy of chromosome 16 and produce individuals with some phenotypic characteristics of Down syndrome, such as cardiovascular defects, neurologic alterations, and retardation of brain maturation as well as early aging (89). Proposed as a good in vitro model to experimentally induce the premature aging of neurons is the transfer of the trisomy 21 from the fibroblast donor cells to neuroblastoma cells.

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