A high frequency of DRw9 and a low frequency of DR1 have been associated with immune deficiency diseases, which may explain these results. In a study of French centenarians, Schachter et al 6 found that ApoE4 was associated with a shorter life expectancy. Because the E4 isoform of ApoE correlates with increased susceptibility to both coronary heart disease and Alzheimer's disease, it is not difficult to understand why the presence of ApoE4 is associated with shorter life expectancy. The higher frequency of the ApoE2 isoform in long-lived individuals is unexpected, given its hypertriglyceridemic effect. Interestingly, a close homologue of ATM in yeast is the gene TEL1, which is involved in telomere maintenance.
Telomeres are a specialized structure at the ends of each chromosomal arm.
These stretches of non-coding DNA prevent certain forms of chromosomal aberration, and, in humans, telomere length seems to diminish in proportion to age. 9 Germ cells and fetal tissues have longer telomeres than do somatic tissues from adults, suggesting that there may be an age-related decline in telomere length. Chromosomes show elevated rates of non-homologous recombination, rapid telomere shortening, and decreased repair of telomeres. The syndrome is caused by a mutant DNA helicase, an enzyme that disrupts the hydrogen bonds that hold the two DNA strands together in a double helix. Recently, myocardial infarction, the leading cause of death in Werner's disease patients, has been shown to be associated with one of the mutations found in the Werner's gene.