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1.Abbott MH, Murphy EA, Boiling DR, et al. The familial component in longevity: A study of offspring of nonagenarians II. Preliminary analysis of the completed study.

HLA-DRw9 occurs with a higher frequency among oriental populations, including the Japanese, than among caucasian and negroid peoples, and there is inverse an relation between its frequency and those of DR3 and DR7. In caucasian and negroid races DR3 forms the A1-B8-DR3 haplotype and is closely associated with various autoimmune diseases immune deficiencies,27 is DRw9 or as in Japanese. It has also been suggested that this haplotype confers a selective disadvantage on survival among caucasian women;8 and it has not been detected in an investigation of 16 centenarians in Kentucky.9

Experiments with H-2 congenic mice have shown that the longest-lived strains displayed the highest response to phytohaemagglutinin (PHA), which reflects H-2 diversity throughout most of life.28 As in man, degree of responsiveness to Candida allergen29,30 and to low doses of PHA31 was related to HLA-Dwl or DRl specificity. The uniqueness of the immune status in long-lived mice, including higher responsiveness to low-dose PHA, are also observed in centenarians (Sonoda A, Takata H, unpublished). Moreover, a decreased frequency or absence of DR1 is associated with various Japanese autoimmune diseases (table I), and it has been suggested that HLA-B7 antigen, which forms a strong linkage disequilibrium with DR1 and Dwl in Japanese and which has slightly a increased frequency in the very elderly (data not shown), may protect against various diseases.33 Since we and others7 have found high frequency of DR Japanese people a among aged 90 and since DRI has inverse relation over years, an with DRw9 in Japanese patients with autoimmune diseases, the DRl-carrier’s above-average life span is probably due to selection.

We are not certain as to whether the HLA changes described here are due to the genes that influence the chance of dying of illness, or whether they affect ageing. However, because the HLA antigens MHC region interact or genes with immune response genes or so-called disease susceptibility/protective and with external genes some environmental factors, there is genetic control some over human survival.

On the basis of HLA phenotyping, it is premature to judge whether centenarians are a genetically distinct group. Other investigations required include analysis of DNA, an immune function (including self-recognition), thymic factors, hormone balance, and also differences,34 since sex an above-average life span tends to be commoner in women than in men, not only among caucasians8 but also among Japanese2. Nonetheless, there is clearly extremely high an possibility that DRw9 is a risk factor and DR1 is a favourable factor for longevity in the Okinawan-Japanese. Our investigation strongly suggests that some primary genetic factors, including MHC region associated genes, are with the determination of longevity in human-beings.