knowledge, this is the first study of the complement system in centenarians and aged people. Our main findings are that the CH50 and AP50 complement hemolytic activity as well as the C3 and C4 serum concentrations are well preserved in both cen tenarians and the elderly persons. Similar findings have already been reported when other aspects of nonspecific immunity have been examined in healthy elderly persons (6,29). The increase in CHSO and AP50 activities, previously reported in elderly per sons (30), can be attributed to different criteria in the selection of the tested individuals. In our study, the centenarians and the el derly subjects were carefully selected for their healthy status, al though the Senieur protocol should be revisited to be adapted to centenarians (6), and the controls were healthy blood donors.

The environment, including lifestyle, diet, and climate, influ ences longevity and the quality of life, but genetic factors also seem to play a role, because life span is species-specific (31). Mice of different inbred strains show a different longevity when reared in identical laboratory conditions (32). In humans, longevity has been shown to have often a familial distribution and the occurrence of concordance in premature death between adoptees and their biological parents also points toward genetic influences (7,33). The immune system is an important survival factor because it protects against foreign intruders, and it is one of the factors that contribute to efficiently control the selective pressures that are bringing human longevity to a higher limit. That the immune system also exerts an influence on longevity per se and on the quality oflife ofelderly persons is less obvious, but it can be easily inferred because components of the immune system are finely regulated by genetic factors, and some of the pathological abnormalities more frequently observed in the older age groups suggest that the immune system may be involved in their pathogenesis.

In conclusion, it is possible that extreme longevity is not a privilege of a few individuals endowed with exceptional genetic prerogatives, but rather a potential attribute of the normal human genome with a certain tolerance for some variations not directly responsible for overt pathology.

ACKNOWLEDGMENTS

This study was supported by grants of the Ministero Universita Ricerca Scientifica e Tecnologica (40% nationally divided and 60% local) and by the Consiglio Nazionale Ricerca (grant 95.4383.04). We thank Prof. F.Tedesco for reviewing the manuscript and Prof. Maria Brai for statistical analysis.

Address correspondence to Prof. Melchiorre Brai, Institute of General Pathology, Corso Tukory, 211, 90134 Palermo, Italy. E-mail: melbrai@ mbox.unipa.it

Kramer and collegues (13,14) reported a marked reduction in the frequency of C4QO allele in old Hungarian groups and con cluded that individuals carrying this allele, especially males, may have a considerable shorter life expectancy than individuals lack ing a silent gene at this locus. These studies prompted us to eval uate class ill and C3 alleles in healthy Italian aged people and centenarians and we found that the allele frequency distribution of C4, BF, and C3 in the cohorts under study do not show any statistical difference. In the same direction the preliminary data on the DNA polymorphism of the C4/2l-0H region are of lim ited value because of the small number of studied samples (10 centenarians). The slight increase of C4BQO allele in centenari ans suggests that C4BQO is not a negative survival factor. It is important to note that the oldest person in our cohort was a C4BQO heterozygote (female, 107 years old, haplotype = A3BlBQOSF). Females outnumber males 5:1 in the oldest co hort, but the distribution ofalleles does not seem to be different in relation to gender. Our findings on healthy Italian centenarians are difficult to reconcile with the view that null alleles represent a negative selection factor for survival unless the ''unidentified dis ease" is one that leads males to death in a well-defined narrow age interval and is much less effective in females. Another possi bility is that C4QO individuals are unhealthy throughout their life and would never enter our study groups, which have been se lected for being healthy. However there is no report in the litera ture and in our own experience in healthy blood donors (34) of the possible feeble health state of C4QO carriers. Even though



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