Autoantibodies to poly(ADP-ribose) polymerase in centenarians: a reappraisal of Grabar's hypothesis.

Background: Centenarians display a characteristic auto- antibody profile, this being the absence of organ-specific autoantibodies and an increase in non-organ-specific auto- antibodies without any full-blown autoimmune disease. Objective: Antibodies directed to the nuclear protein poly(ADP-ribose) polymerase (PARP) were frequently found in the sera of patients affected by autoimmune diseases. This study aims at investigating the presence of circulating auto- antibodies directed against PARP-1 in normal subjects, and searching for a possible correlation between level of circulat- ing autoantibodies and age. Methods: The presence of anti- bodies to PARP was monitored by ELISA according to a previ- ously developed protocol. Data were analysed by parametric statistics (unpaired t test, :2 test). Results: Our study per- formed on 33 centenarians and 66 subjects of age ranging from 12 to 80 years shows that circulating autoantibodies to the nuclear enzyme PARP, previously described in autoim- mune diseases, are present in the sera of normal healthy people and increase with age. Conclusions: Taking into ac- count the role of PARP-1 in DNA damage and apoptosis, the data are compatible with Grabar’s hypothesis, which pro- posed several decades ago that ‘autoreactive antibodies represent a physiological system for disposing the products of metabolism and catabolism’, thereby helping to attain longevity.