Disorders of Accelerated Aging

Several disorders of accelerated aging have been identified. Study of these disorders may yield information about controlling the rate of aging.

Progeria: In progeria, which is rare, children appear to age rapidly and, during childhood, exhibit several features similar to changes normally observed in the elderly (eg, baldness, osteoporosis, dry and wrinkled skin). However, progeria also has other features; for example, most children affected by progeria do not develop gonadal activity, and many are short in stature. Thus, progeria is not exactly a model of accelerated aging.

Werner's syndrome produces sclerodermal skin changes and baldness, which make affected children appear old, producing an immediate sense of premature aging. Other features typical of senescence include premature cataracts, muscular atrophy, glucose intolerance, a high incidence of cancers (some of which are rare in unaffected people), and early death due to atherosclerosis. However, the CNS is largely spared. The gene involved in Werner's syndrome codes for a DNA helicase, an enzyme that unwinds DNA to allow replication and possibly transcription. This discovery has led to speculation that during normal senescence, many age-related impairments may result from impairments in the helicase mechanism; however, this hypothesis has not been studied systematically.

Wiedemann-Rautenstrauch syndrome and Hutchinson-Gilford syndrome also produce premature scleroderma, baldness, and other senile changes in children. The genetic basis of these syndromes remains undetermined.

Down syndrome: Down syndrome produces changes typical of senescence, including glucose intolerance, vascular disorders, a high incidence of cancers, hair loss, degenerative bone disorders, and premature death. Down syndrome greatly impairs the CNS, usually producing retardation and accelerating the accretion of neuritic plaques and neurofibrillary tangles characteristic of Alzheimer's disease. Because Down syndrome results from duplication of all or a small part of chromosome 21, its cause was originally thought to be duplication of the gene for -amyloid. Mutations of this gene, located on chromosome 21, have been implicated in Alzheimer's disease. However, although the duplicated region that produces Down syndrome is near the
-amyloid gene, the best evidence suggests that Down syndrome may occur without duplication of the -amyloid gene. The specific gene or genes involved in Down syndrome remain undetermined.

This topic was last updated June 2006.