In the present study we have investigated the prevalence of organ-specific and non organ-specific autoantibodies in 26 healthy centenarians (6 men, 20 women; age range 101-106 years), using as controls 54 healthy old (33 men and 21 women, age range 71-93) and 56 young subjects (29 men and 27 women, age range 26-60). We assayed sera of each group for the following organ-specific autoantibodies, anti-gastric mucosa (anti-PCA), anti-thyroglobulin (anti-Tg) and non organ-specific autoantibodies, anti-cardiolipin (anti-APA IgG and IgM), anti-nuclear antigens (anti-ANA), anti-double strand DNA (anti-ds-DNA), anti-extractable nuclear antigens (anti-ENA). Finally, natural anti-alpha-galactosyl (anti-alpha-GAL) antibodies were also analyzed. As expected, in the old subjects there was a significant increase of prevalence of anti-Tg and anti-PCA autoantibodies. By contrast, in centenarians the prevalence of organ specific anti-Tg and anti-PCA antibodies was not significantly different from that observed in controls aged less than 60 years. The prevalence of non organ-specific autoantibodies anti-APA (IgG), anti-APA (IgM), anti-ANA, was significantly increased both in the elderly and centenarians when compared with the prevalence observed in sera from the young. Anti-ENA and anti-dsDNA antibodies were not detected in all groups studied. Finally, the prevalence of natural anti-alpha-GAL antibodies significantly increases with age, including centenarians. In conclusion, we confirm and extend the results previously obtained by other authors. In fact, as already described, the prevalence of organ-specific autoantibodies in the elderly is not seen after the tenth decade of life. Interestingly, the prevalence of non organ-specific autoantibodies is instead increased in these subjects, suggesting that different mechanisms are involved in the pathogenesis of these autoantibodies. Particularly, these autoantibodies could be the expression of a damaged tissue process rather than of an autoimmune one, as suggested by data concerning natural antibodies.