Syndromes of accelerated aging.
A systematic review of the more than 2,000 genetic loci of man cataloged by McKusick indicated that approximately 7% may play a role in modulating the rates of development of various aspects of the senescent phenotype. Assuming an upper limit of about 100,000 loci in man, numerous alleles at approximately 7,000 loci could be contributing to characteristic patterns of aging in individual human beings. Point mutations or chromosomal aberrations involving such loci may result in various progeroid syndromes. These have been classified into two categories: segmental progeroid syndromes, which involve multiple aspects of the senescent phenotype, and unimodal progeroid syndromes, in which predominantly one aspect of the phenotype is involved. Two different examples of segmental progeroid syndromes were discussed: the Werner syndrome (an autosomal recessive) and the Down syndrome (trisomy 21). Examples of unimodal progeroid syndromes included familial hypercholesterolemia (accelerated atherogenesis), xeroderma pigmentosum (acceleration of skin aging, including age-related neoplasms), and certain forms of intestinal polyposis (acceleration of adenocarcinoma of the colon). It is remarkable and encouraging that the biochemical genetic basis of many progeroid syndromes, including all of those mentioned above, may be amenable to investigation with cultured mesenchymal somatic cells from individual subjects. For example, cells from patients with the Werner's syndrome have a striking limitation of their in vitro replicative life-spans and undergo extensive chromosomal rearrangements. These abnormalities are presumably related to an enzyme deficiency which, in principle, could be identified by biochemical studies of cultured cells.
D000483:Alleles; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D004314:Down Syndrome / Q000235:genetics; D005796:Genes; D005808:Genes, Recessive; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics; D007417:Intestinal Polyps / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D011371:Progeria / Q000145:classification / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics; D013577:Syndrome; D014898:Werner Syndrome / Q000235:genetics; D014983:Xeroderma Pigmentosum / Q000235:genetics