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Accelerated Aging: Human Progeroid Syndromes

Down Syndrome

Down syndrome occurs about once in seven hundred births and is characterized by delayed and incomplete development as well as degeneration of many organ systems. Down syndrome exhibits an early onset of many aging characteristics, including graying and loss of hair, hearing loss, cataracts, increased tissue lipofuscin, and degenerative vascular disease, as well as increased frequency of autoimmunity and cancer, particularly childhood leukemia. Multiple neurological abnormalities, including early onset of senile dementia similar to that associated with Alzheimer's disease, may result from both decreased proliferation and increased apoptosis of neurons. Individuals with Down syndrome usually die by the age of forty.

Down syndrome is caused by having three (instead of two) copies of part or all of human chromosome 21, making it genetically much more complex than other segmental progeroid syndromes. Hypothetically, the extra chromosome alters gene expression levels that, in turn, cause metabolic defects that result in both the developmental problems and degenerative effects of Down syndrome. Chromosome 21 harbors the gene for the amyloid precursor protein. Increased production of this protein could be a factor in amyloid plaque development, which is diagnostic for senile dementia associated with Down syndrome and Alzheimer's disease. This chromosome also contains the Cu/Zn (copper/ zinc) superoxide dismutase gene that is involved in the metabolism of reactive oxygen species. Imbalances in oxidative metabolism could lead to increased cellular damage, a scenario consistent with both the increased lipofuscin and oxidative DNA damage observed in Down syndrome and the proposed relationship between accumulation of oxidative damage and aging characteristics. However, the contribution of any particular gene on chromosome 21 to specific premature aging characteristics associated with Down syndrome remains unclear.

Additional topics

Medicine EncyclopediaAging Healthy - Part 1Accelerated Aging: Human Progeroid Syndromes - Progeroid Syndromes As Models Of Aging, Down Syndrome, Adult Progeria (werner Syndrome), Progeria (hutchinson-gilford Syndrome)