Mechanisms of Ageing and Development 122 (2001) 445–462 Review Immunogenetics of longevity. Is major histocompatibility complex polymorphism relevant to the control of human longevity? A review of literature data Calogero Caruso a, *, Giuseppina Candore a , Giuseppina Colonna Romano a , Domenico Lio a , Massimiliano Bonafe ` b , Silvana Valensin b , Claudio Franceschi b,c a Dipartimento di Biopatologia e Metodologie Biomediche, Uniersita ` di Palermo, Corso Tukory 211, 90134 Palermo, Italy b Dipartimento di Patologia Sperimentale, Uniersita ` di Bologna, Bologna, Italy c Dipartimento di Ricerche Gerontologiche, Istituto Nazionale di Riposo e Cura per Anziani di Ancona, Ancona, Italy Received 23 August 2000; received in revised form 15 November 2000; accepted 30 November 2000 Abstract Literature data suggest that human longevity may be directly correlated with optimal functioning of the immune system. Therefore, it is likely that one of the genetic determinants of longevity resides in those polymorphisms for the immune system genes that regulate immune responses. Accordingly, studies performed on mice have suggested that the Major Histocompatibility Complex (MHC), known to control a variety of immune functions, is associated with the life span of the strains. In the last 25 years, a fair number of cross-sectional studies that searched for the role of HLA (the human MHC) genes on human longevity by comparing HLA antigen frequencies between groups of young and elderly persons have been published, but conflicting findings have been obtained. In fact, the same www.elsevier.com/locate/mechagedev * Corresponding author. Tel.: +39-091655911; fax: +39-091655933. E-mail address: marcoc@unipa.it (C. Caruso). 0047-6374/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII:S0047-6374(00)00255-4