Masafumi Akisaka

Functional alteration of granulocytes, NK cells, and natural killer T cells in centenarians

The immune system in centenarians was characterized as elevated levels in the proportion and number of granulocytes, NK cells, and extrathymic T cells (including NKT cells) in the peripheral blood. Conventional T cells, abundant in youth, were decreased in proportion and number. In addition to this numerical change in centenarians, the function was significantly altered in comparison with that in middle-aged subjects. The phagocytic function and cytokine production of granulocytes in centenarians increased whereas the production of superoxides from granulocytes decreased. This tendency was almost the same in both healthy and unhealthy centenarians. IFN gamma production by NK and extrathymic T cells in centenarians seemed to be augmented and resulted in an elevated level of serum IFN gamma. Possibly due to the effect of this endogenous IFN gamma, the proportion of CD64(+) (Fc gamma RI) cells among granulocytes was elevated. The expansion of CD64 antigens on granulocytes is known to be regulated by IFN gamma and to be associated with their induction of phagocytosis. These results suggest that the immune system of centenarians is not merely impaired, but altered in terms of the number and functions of granulocytes, NK cells, NKT cells.

Serum globulin levels and activities of daily living in centenarians

Serum globulin levels in 101 centenarians (77 women, 24 men) were analyzed by zonal electrophoresis and immunoglobulin assays. Six subjects showed an M band in electrophoretograms. Five M bands were immunoglobulin G (IgG) type and one was IgA. One subject was suspected to suffer from IgG-type multiple myeloma, and the others were thought to have essential (benign) monoclonal gammopathy. The relationship between serum globulin levels and activities of daily living (ADL) was studied in remaining 95 subjects. There were 21 rank-J (free-living), 25 rank-A (unable to go outside without help), 23 rank-B (bedridden but able to sit on the bed), and 26 rank-C (completely bedridden) centenarians. The mean serum alpha 1-, alpha 2-, and beta-globulin level in the rank-J centenarians was at the upper limit of the normal adult range. The mean alpha 1-globulin levels in rank-B (3.3 +/- 0.4%) and C (3.4 +/- 0.5%) subjects were significantly higher than those in rank-J (2.9 +/- 0.3%) centenarians. The mean serum gamma-globulin level of rank-J centenarians (16.9 +/- 3.7%) was within the normal range. The mean gamma-globulin levels in rank-B (21.0 +/- 2.7%) and C (22.8 +/- 4.9%) subjects were significantly higher than that in rank-J centenarians. The mean immunoglobulin G concentrations in rank-B (1.620 +/- 304 mg/dl) and C (1.720 +/- 392 mg/dl) subjects were significantly higher than those in rank-J centenarians (1.320 +/- 361 mg/dl) and in normal adults (1.150 +/- 235 mg/dl). IgA concentrations in all centenarians were higher than in normal controls. There was no significant difference in IgA or IgM concentration between rank-J subjects and those in other ranks. Serum globulin levels measured with electrophoresis, and the immunoglobulin concentrations, can be valuable indicators of the ability to perform activities of daily living, and may be useful predictors of subclinical diseases or morbidity in centenarians.