Immunodeficiency in old age.
Aging is a multi-facetted process, but the deterioration of the immune function seems to play a central role in this context. Paradoxically, immune reactivity against exogenous antigens declines during aging while autoimmune reactivity increases. One of the aims of our investigations on the function of the senescent immune system was to define immune parameters of 'normal' aging, i.e. those not dependent on underlying diseases. Specifically, our interest was focused on the possible role of an altered lipid metabolism of cells of the immune system during aging. The known decrease of plasma membrane fluidity of lymphoid cells and monocytes in higher age may be one of the factors responsible for the nonoptimal functioning of the immune system. This property, in turn, seems to be based on an altered lipid metabolism. Specifically, we have evidence that the finely tuned balance between the transport of cholesterol to and from lymphoid cells via the environment and the intracellular cholesterol biosynthesis seems to be disturbed with increasing age. This conclusion is drawn from experiments where low-density lipoprotein (LDL) and high-density lipoprotein (HDL) receptor activity is assessed using fluorescently labeled lipoproteins in fluorescence-activated cell sorter (FACS) analyses. LDL receptor uptake is unexpectedly increased in the elderly, but LDL receptor regulation, and serum LDL composition itself seem to be normal. Preliminary data point out the possibility that the efflux of cholesterol via HDL may be insufficient. Attempts to modulate plasma membrane fluidity by means of the phospholipid mixture 'active lipid 721' (AL 721) showed that this drug, in contrast to literature reports, is not a 'membrane fluidizer' but rather exerts this effect as a nutrient for lymphocytes and monocytes.
Wick
G
G
Institute for General and Experimental Pathology, University of Innsbruck, Medical School, Austria.
Huber
L A
LA
Offner
F
F
Winter
U
U
Böck
G
G
Schauenstein
K
K
Jürgens
G
G
Traill
K N
KN
D000375:Aging / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000209:etiology*; D050356:Lipid Metabolism; D008214:Lymphocytes / Q000378:metabolism
D002784:Cholesterol