Study on the lipid composition of aging Fischer-344 rat lymphoid cells: effect of long-term calorie restriction.

Long-term calorie restriction (LCR) is widely known to increase the survival rate of laboratory rodents and appears to retard the aging and senescence process. The present study was undertaken in Fischer-344 male rats maintained on ad libitum (AL) or LCR (40% less food intake than AL starting at 6 weeks of age). Age-associated changes in the proliferative response of lymphoid cells to mitogenic stimuli were studied in relation to alterations in the fatty acid composition of adherent and non-adherent-enriched subpopulations of spleen cells. Increases in spleen cell long-chain highly unsaturated fatty acids (20:4, 22:4 and 22:5) were accompanied by decreases in linoleic acid (18:2) in aging AL-fed rats. However, LCR stabilized levels of 18:2 and prevented the rise in highly unsaturated fatty acids. In addition, LCR markedly modulated the fatty acid profiles of thymocytes and bone marrow cells. A 70% decline in concanavalin A (Con A) stimulated [3H]thymidine uptake of spleen cells from AL animals was normalized by LCR. Splenic reduced glutathione (GSH), a potential modulator of the mitogenic response, was unaffected by age and nutritional regimen. Thus, normalization of lymphoid cell fatty acid composition by LCR parallels the preservation of mitogenic responsiveness to Con A.