histocompatibility complex (MHC) is one of the gene systems influencing ageing.3 The HLA antigens in man, especially those associated with the HLA-D region, are closely related to autoimmune diseases, cancer, and other such malignancies, as well as to immune responsiveness.4 However, it is not yet known whether such a relation exists between HLA and longevity, though the advantage of HLA heterozygosity5-7 and the disadvantage of AI-B8 haplotype for caucasian women8 have been suggested earlier. The number of centenarians known to have been investigated for the distribution of HLA antigens has far so consisted of 11 Japanese subjects’ and 16 caucasians.9

INFLUENCE OF MAJOR HISTOCOMPATIBILITY COMPLEX REGION GENES ON HUMAN LONGEVITY AMONG OKINAWAN-JAPANESE CENTENARIANS AND NONAGENARIANS

HAJIME TAKATA1 ISHII3

HAJIME TAKATA1 MAKOTO SUZUKI2 TOSHIHARU ISHII3 SUSUMU

Laboratory for Histocompatibility and Clinical Immunology, Department of Clinical Laboratories, Keio University School of Medicine, Tokyo;1 Department of Community Medical Service, University of the Ryukyus, Okinawa;2 Department of Pathology, Tokyo Medical College, Tokyo;3 and Department of Laboratories, National Medical Saitama,

Okinawa islands, the southernmost part of Japan, are known for the longevity of their populations; the life average expectancy there was 74-52 years for men and 81 72 years for women in 1980 and, according to Ministry of Health and Welfare data,lO in 1984 about 5 per 100 000 of the population centenarians.2 were

Summary

phenotypes in 82 centenarians and 20 nonagenarians in Okinawa, Japan, were compared with those in other healthy adults in various age-brackets. Subjects aged over 90 had an extremely low frequency of HLA-DRw9 and an increased frequency of DR1. In this age-group the relative risk of and corrected (for number of antigens) p value for HLA-DRw9 were 5&middot;2 and 0&middot;0001, respectively; those for HLA-DR1 were 13&middot;3 and 0&middot;0367, respectively. Since a high frequency of DRw9 and a low frequency of DR1 are associated with autoimmune or immune deficiency diseases, the genetic protection against these disorders may contribute to longevity.

Since 1979, 82 strictly verified centenarians and 20 nonagenarians who lived the Okinawa islands on were investigated to compare HLA-A, B, C, DR, and DQ antigen phenotypes with those of average, normal adults of the same geographic region. In this report, we present the data which suggests that some primary genetic factors, including MHC region genes, are associated with human longevity.

Subjects and Methods

Subjects

The blood samples collected from 82 centenarians (18 were males/64 females) aged 100 to 106 years (average 101. 1 years), 20 nonagenarians (4 males/ 16 females) aged 90 to 99 years (average 96-5), and 159 healthy adults (78 males/81 females), aged 18 to 85 years (average 58-1). Only those found on clinical examination to be in good general health were included in the survey.

Introduction

IT is very rare for man to live beyond 100 years. Environmental factors such lifestyle, diet, and climate as would have a strong influence on longevity. Since long life runs in families,12 so genetic factors probably also contribute to longevity.

The age given by centenarians and nonagenarians was checked against family registers, age of subject at time of major event such as birth records, subjects’ personal recollections, and family war, lineage.2 In cases of even the slightest doubt, subjects were excluded from the

The clear-cut relation between maximum lifespan in mice and the H-2 system suggests that the major

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