E. Naumova et al. / Experimental Gerontology 39 (2004) 637–644

consistent with a healthy immune status of elderly people in our study group.

1999, 2001). In the present study it was shown that IL-10 genotype 21082G/A, 2819 C/C, 2592 C/C related to intermediate production was positively associated, while genotype 21082A/A, 2819 C/T, 2592 C/A related to low level of production was negatively associated with long- evity in Bulgarians. These results confirm data, showing that longevity is associated with genotypes coding for anti- inflammatory profile (Lio et al., 2002; Bonafe et al., 2001). Recent data indicated that pro-inflammatory profile is associated with increased mortality in elderly individuals (Franceschi et al., 2000). Additionally, our study on cytokine gene profiles demonstrated that the effect of IL- 10 gene polymorphism is modulated by IL-6 and IFNg genotypes associated with low level of production of these pro-inflammatory cytokines.

generations longevity members we did not observed HLA alleles and haplotypes associated with autoimmunity. Our data also indicate an association of longevity with genotypes coding for anti-inflammatory cytokine profile. In addition, we did not observed the ‘immune risk phenotype’ which is a marker of an increased inflammatory activity. Based on the results of this study, it seems reasonable to suggest that a combination of specific immunogenetic and immunophe- notype profiles could contribute to successful aging and to maintaining healthy status in elderly.

Acknowledgements

immune factors in longevity we also searched for changes in the immune phenotype profile with aging. The results of the present study demonstrated markedly decreased CD8 þ T cell subsets in elderly people. Our observation of lower CD8 cell levels in middle aged and young family members supports the concept that genetic factors influence the regulation of lymphocyte subpopulations as well (Hall et al., 2002). The lowest CD8 numbers were seen in the old individuals. It will be reasonable to expect that although initially low compared to the general age-matched popu- lation, CD8 cell values will decrease with aging in the younger individuals of these families. Loss of CD28 expression with increasing age resulting in decline of the proportion of CD28 positive T cells (Effros et al., 1994; Effros, 2000) and an increase of CD8 þ 28 2 T cells (Nociari et al., 1999) have been reported. The old individuals in our study group have low CD3 þ CD8 þ cell values associated with a major decrease of the CD8 þ 28 þ cell subset, but we did not found an increase of CD8 þ CD28 2 cells within the lymphocytes. Looking at the CD8 þ lymphocyte subpopulation, CD28 negative cells were predominant compared to the CD28 positive cells. Thus, an increase in proportion of CD28 negative cells in the elderly do not necessarily equate with the increased number of such cells. These changes in the T cell subset profile in old individuals were supported by our observation of progressive age related decline of CD8 þ CD28 þ cells and a redistribution of CD28 negative and CD28 positive cells within the CD8 þ lymphocytes in the different family generations. It has been demonstrated that CD28 2 T cells are frequently CD57 þ cells (Azuma et al., 1993). Our data showed decreased values of CD8 þ 57 þ cells in elderly compared to middle aged controls with no significant ^ ^ changes of their proportion (29.2 9.1% vs. 29.4 9.4%) within the CD8 þ cells. Therefore, in this study we did not observe the ‘immune risk profile’ characterized by elevated CD8 þ , CD8 þ 28 2 , CD8 þ 57 þ cells, decreased CD4 þ T cells, and inverted CD4/CD8 index (Wikby et al., 2002) in old people. Taking into account the above considerations, it could be speculated that our results are

The authors are grateful to the volunteers for making this study possible. This investigation has been done within ImAginE and was supported in part by a research grant from T-CIA project N-QLK6-CT-2002-02283.

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