Calories,Cell Proliferation,and Proviral Expression in Autoimmunity and Cancer

Abstract

Healthful Consequences of Reducing Dietary Calories. Reduced calorie intake (RCI) to levels 20-40% less than ad libitum intake without essential nutrient deficiency extends the latency to onset and reduces the frequency of neoplastic and autoimmune disease in rodents, and extends the healthful longevity of many species across wide phylogenetic differences (1-4). The beneficial consequences of RCI have been demonstrated in disease pattern surveys of large populations of outbred and inbred rats, and long-lived inbred and hybrid mice fed semipurified diets which vary only in caloric level. In these surveys, cumulative frequencies of mortality due to neoplasia and other diseases among calorie-restricted cohorts were lower and maximum longevities were extended.

Healthful longevity has also been extended and onset of disease has been delayed by RCI in short-lived inbred, hybrid, and mutant mice. Mice of short-lived strains are genetically prone to develop and die at a young age of a progressive disease syndrome that ordinarily develops with advanced age. Diseases of short-lived mice delayed or prevented by reducing dietary calories include the systemic amyloidosis of senescence-accelerated mice (5), the systemic lupus erythematosus-like syndrome of B/W F₁ mice (6, 7), the breast cancer of C3H mice (8-13), the nephrophthisis of kd/kd mice (14), the lymphoproliferative syndrome of autoimmune-prone MRL mpj lpr/lpr mice (15, 16), and the thymic lymphosarcoma of AKR mice (17). The discussion presented here concerns observations of extended healthful longevity in three of these short-lived cancer-prone or autoimmunity-prone strains of mice.

Extension of healthful longevity depends quite specifically on energy restriction and is not the consequence of altered dietary composition. Although incidences of diseases can be altered by variation in both type and quantity of certain dietary variables independent of calorie level, restriction of or variation in the type of dietary fat (10, 18), protein (7, 19-21), or carbohydrate (22, 23), or supplementation with vitamin E (24) or other antioxidants (25) or overall vitamin supplementation (26) without restriction of calories does not increase the maximum life span of rodents.