The idea of the existence of longevity genes is difficult to understand in the light of Darwin’s theory of evolution. We can hardly expect an extension of life span after 85 years of age to be advantageous for the preservation of the species. H a y f l i ~ kh,o~w~e ver, has recently proposed an interesting theory on this topic:

In order to insure maximum parental fitness for survival of slowly maturing human progeny, there would be a selective advantage for parents to maintain their physiolog- ical vigor after sexual maturation. The reserve capacity, present in virtually all or- gans, is the essential element in determining postdevelopmental longevity.

CONCLUSION

The age-related differences in HLA antigens should however never distract us from the importance of prevention, life style and other nongenetic factors which contribute to reach an active, healthy and independent old age.

ANNALS NEW YORK ACADEMY OF SCIENCES

SUMMARY

both in experimental animals and in the human species. In mice, genes in the major histocompatibility complex (MHC) are associated with a significant effect on life span. Results of analogous studies in man are confusing and contradictory. We have therefore investigated the question of an association of the human leucocyte antigen (HLA) and longevity in a large and ethnically homogeneous population. Our study population consisted of all 964 available inhabitants aged 85

on life span. Results of analogous studies in man are confusing and contradictory. We have therefore investigated the question of an association of the human leucocyte antigen (HLA) and longevity in a large and ethnically homogeneous population. Our study population consisted of all 964 available inhabitants aged 85 years and over in the Dutch community of Leiden (pop. 104,000). Our control group comprised 2444 young inhabitants, aged 20-35 years, with an identical ethnic and demographic background. In addition, control groups of different age- brackets from the same region were used.

higher in the group of 85 years and over, as compared to the control group, aged 20-35 years. Both differences were more evident in females. No major disease associations with HLA-B40 or HLA-DRS have been reported. It is unlikely that these results are a chance observation: the overall similarity of the HLA pattern of the old and young age groups is a confirmation of their identical ethnic and demographic background and the changes as observed in the different age-groups were gradual. The biological meaning of these results is still unclear.

ACKNOWLEDGMENTS

We thank Professor J. Vandenbroucke for valuable and indispensable epide- miologic advice; Mrs. E. P. J. M. Mudde-Hoogveld for collecting the derno- data; Mr. Jipje Krebbers for correction of the English text; Mrs. M. den for the preparation of the manuscript; and all participants of 85-plus project in Leiden, both active and passive, who were, and will be, a source of inspiration.

REFERENCES

I . SMITH,G . S. & R. L. WALFORD

Influence of the main histocompatibility com- plex on ageing in mice. Nature

-

SMITH,G . S. & R. L. WALFORD

Influence of the H

and H

histocompatibility systems upon life span and spontaneous cancer incidence in congenic mice. In Genetic Effects on Ageing. D. Bergsmaand D. E. Harrison, Eds.

-

National Foundation-March of Dimes. Alan R. Liss. New York.

MEREDITHP, . & R. L. WALFORD.

Effect of age on response to T and B cell mitogens in mice congenic at the H-

region. Immunogenetics

:

YUNIS,E . J., G. FERNANDESP,.

TEAGIJE

, . SUTMA&N R. A. Goon.

The thymus, autoimmunity and the involution of the lymphoid system. Zn Tolerancc, Autoimmunity and Aging. M. M. Sigel, Ed.

-

Charles C. Thomas. Springfield.

ABBOTT,M . H., E. A. MURPHYD,. R. BOLLING& H. ABBEY.

The familial component of longevity, a study of offspring of nongenarians.

Preliminary analy- sis of the completed study. Hopkins Med. J.

:

-

PALMOREE, . B.

Predictors of the longevity difference: a

-year follow-up. Gerontologist

:

-

SORENSENT, . I. A., G. G. NIELSEN,P . K. ANDERSEN& T. W. TEASDALE

Genetic and environmental influences on premature death in adult adoptees. N. Engl. J. Med.

:

-

YUNIS,E . J., G. FERNANDESP,. 0. TEAGIJE0, . SUTMA&N R. A. Goon. 1972. The thymus, autoimmunity and the involution of the lymphoid system. Zn Tolerancc, Autoimmunity and Aging. M. M. Sigel, Ed. 62-119. Charles C. Thomas. Springfield. ABBOTT,M . H., E. A. MURPHYD,. R. BOLLING& H. ABBEY.1 974. The familial component of longevity, a study of offspring of nongenarians. 11. Preliminary analy-

LAGAAY et al.: LONGEVITY & HEREDITY

TIWARI,J . L. & P. I. TERASAKIE, ds.

In HLA and disease associations.

-

Springer-Verlag Inc. New York.

WALFORDR, . L., G. S. SMITH,P . J. MEREDITH& K. E. CHENEY

Immuno- genetics of Aging. In The Genetics of Aging. E. L. Schneider, Ed.

-

Plenum Publishing Corporation. New York.

TAi

A, H., M. SUZUKIT, . ISHI, S. SEKIGUCH&I H. IRI.

Influence of major histocompatibility complex region genes on human longevity among Okinawan- Japanese centenarians and nonagenarians. Lancet ii:

-

MACUROVAH,. , P. IVANYIH, . SAJDLOVA& J. TROJAN

HL-A antigens in aged persons. Tissue Antigens

-

YARNELLJ,. W. G., A. S. ST. LEGER,I . C. BALFOUR& R. B. RUSSELL

The distribution, age effects and disease associations of HLA antigens and other blood group markers in a random sample of an elderly population. J. Chon. Dis.

-

HANSENH, . E., J. V. SPARCK& S.

LARSEN

An examination of HLAfrequen- cies in three age groups. Tissue Antigens

:

-

BENDERK, .,A . MAYEROVAB,. KLOTZBUCHERK,. BURCKHARD&T C . H.

No indication of postnatal selection at the HL-A loci. Tissue Antigens

:

-

BLACKWELDEWR., C., K. K. MITTALP, . M. MCNAMAR&A F. J. PAYNE

Lack of association between HLA and age in an aging population. Tissue Antigens

-

GREENBERGL,. J.