Progress in nutritional immunology.

Optimum but balanced food intake maintains healthy growth and disease-free lifespan. However, imbalanced and over-nutrition promotes obesity, diabetes, malignancy, osteoporosis, infectious diseases, etc. In 1936, McCay reported that calorie restriction prevents weight gain and extend lifespan in rodents. In early 1970, Dr. Good at University of Minnesota and Dr. Walford at UCLA began studies in mice by reducing protein and calorie intake and studying their impact on immune function. Dr. Good's group (Jose, Fernandes, Kramer, Cooper, Day, etc.) reported changes in humoral and cellular immunity at present known as innate and adaptive immune function. Later, much interest was devoted by late Dr. Good on studying the role of calorie restriction (CR) and the role of zinc on immunity, particularly their role on aging, autoimmunity, and malignancy. Both functional role of T-cells, NK-cells and B-cells and their interaction during CR was studied extensively. We recently decided to pursue the beneficial effects of n-3 fatty acids (fish oil) with and without CR on controlling autoimmune-disease in NZB x NZW F1 mice. Our results indicated that n-3 FA when fed ad-libitum prolongs lifespan higher than commonly consumed n-6 FA (corn oil) in these mice. Moreover, n-3 FA + CR is found to be more effective than n-6 FA + CR. Some of the beneficial changes by n-3 FA include enhancing antioxidant enzymes and lowering Th-1/Th-2 cytokines, adhesion molecules, COX-2/PGE(2) levels, pro-inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha etc. The decreased pro-inflammatory cytokines were also found to protect against bone loss in OVX mice. Further, Fat-1 transgenic mice (which make n-3 FA endogenously in vivo from n-6 FA) when fed CR revealed decreased NF-kappaB and AP-1 activity and increased expression of life-prolonging gene SIRT1. Also CR and n-3 FA decreases body weight and increases insulin sensitivity, as well. Thus, to prevent obesity decreased calorie intake with n-3 FA supplement is far more effective and may have protection against CVD, malignancy, autoimmunity, and osteoporosis. The CR studies undertaken in primates and recently in humans are showing very encouraging results. In order to understand more precisely the role of diet and nutrition, new approaches exploring the link through nutrigenomics, proteomics and metabolomics may soon provide insight into controlling age-related diseases by following a balanced food intake.