Results: The genotype frequencies of individuals homozygous for allele A (AA), heterozygous for alleles A and C (AC), and homozygous for allele C (CC) were 35% (n = 142), 42.7% (n = 189), and 17.2% (n = 69), respectively (Table 2). The allele frequencies for allele A and allele C were 59.1% and 40.9%, respectively (Table 2), and the genotype frequency was found to be in Hardy-Weinberg equilibrium (P-value 0.59).

The relationship of aging phenotypes with HSP70-1 genotype is shown in Tables 3-6. Of all the age-related parameters studied, only self-rated health and relative self-rated health (compared to others of the same age) showed an association (P-values of 0.0046 and 0.018, respectively) with the polymorphism at 110 (Tables 5 and 6). As evident from Tables 5 and 6, it is the heterozygous individuals who are more inclined to rate their health as poor, very poor, or worse.

Discussion: Aging and longevity are highly complex traits influenced by genes, environment, and chance (Rattan 2003). The molecular basis of inherited components in aging is far from clear. For studying the genetic basis of human longevity, gene-longevity association studies have been a popular and useful approach. Although a number of genes have been studied for their association with human longevity, the overall picture still remains unclear (Caruso et al. 2001). This is due to various confounding factors that affect the longevity association studies, such as heterogeneity, which may affect the Hardy-Weinberg equilibrium of the population on which such studies are carried out. 

In our study, we took a group of 400 individuals aged 70-91 years from LSADT who have been scored for parameters characteristic of successful/unsuccessful aging. These parameters have been studied for their association with polymorphism at 110 of HSP70-1. Of all the parameters studied, self-rated health (scored both in absolute terms and in relation to others of the same age) shows a striking association (P-value 0.0046 and 0.018, respectively). This self-rated health represents an individual's overall sense of physical well-being and has been shown to be a predictor of survival at older ages (McCallum et al. 1994) and a better indicator of future survival than objectively measured health status (Mossey and Shapiro 1982). In our series, we observed a lower health score in the heterozygous individuals. This seems somewhat surprising, first because Altomare et al. found lower survival in females homozygous for allele A (AA genotype), and second because it is difficult to envision a molecular mechanism causing phenotypic domination in heterozygotes. We also did a gender-specific analysis for the association of self-rated health with the 110A > C polymorphism but did not find any sex specificity for this association (data not shown).

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