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.