LYMPHOCYTE SUBSETS AND NATURAL-KILLER-CELL ACTIVITY IN HEALTHY OLD-PEOPLE AND CENTENARIANS

The contribution of the immune system to healthy aging and longevity is still an open question. For this reason, sev- eral immune parameters (T, B, and natural killer [NK] cell subsets; non-major histocompatibility complex [MHCI- restricted cytotoxic activities, ie, natural and redirected kill- ing [RDK] activities) were studied in a total of 138 healthy subjects of different ages, from 4 t o 106 years of age, in- cluding 26 centenarians. The major age-related modifica- tions were the following: (1) a decrease in the absolute number of T lymphocytes (CD3’). involving both CD4+ and CD8+ subsets, accompanied by a marked concomi- tant increase in the number of activated T cells (CD3+, HLA-DR+); (2) a marked decrease in the number of B lym- phocytes (CD19+); and (3)an increase in the number of cells with markers of NK activity and of T lymphocytes able tomediatenon-MHC-restricted cytotoxicity.Thesemodifi- cations linearly progressedwith age and centenariansfolowed the trend, suggesting that their immune system did not escape the aging process. However, other immunohe- matologic parameters (numberof redbloodcells, platelets, and leukocytes) and important immune functions, such as cytotoxic activities (NK and RDK cell activities), were well preservedthroughoutlifeuntilthelastdecadesoflife.Un- expectedly, in apparently healthy middle-aged subjects, a decrease of cytotoxic activities was observed in compari- son with those of both young controls and centenarians. In conclusions, our data suggest that in centenarians some immune responses are kept at a high level of efficiency, likely contributing to their successful aging. However, this selected group of people does not escape the aging pro- cess, as shown by the progressive derangement of a vari- ety of immune parameters.