Calories versus protein inonset ofrenal disease in NZB xNZW mice

Autoimmunity-prone (NZBx NZW)F1 (B/W)female miceareusedasamodelofhumanlupus erythematosus. Whenfull-fed, these micedieofglomerulone- phritis between 7and11(average 9)months ofage. Whenfood intake isrestricted to60%ofcalories, theonset ofthis disease isdelayed andthemicelive greatly prolonged lives free of disease. Since high protein intake iscommonly associated with acceleration ofkidney damage inhumansandexperimental animals, thecurrent experiments weredesigned toemploy diets inwhichprotein concentration wasashighaspossible. The observations demonstrate clearly thatwiththismodelof autoimmune disease, total calorie intake (fromwhatever source) exerts anoverriding influence onlife span. A higher calorie intake leads toearly death andrestricted-calorie intake leads toanincreased life span. WhenB/Wmicearefull-fed, withrespect tocalories, feeding diets ofgreatly differing protein composition didnotinfluence life spansignificantly. By contrast, calorie restriction ofdiets, evenofveryhigh protein content oroflower protein content, greatly prolonged life of B/Wmice. Evenwithexceedingly high protein intake (>83% ofthecalories) itisnotproteinper sebutthetotal calorie intake that exerts thegreatest influence that determines length oflife inmiceofthisautoimmunity- andglomerulonephritis-prone strain. Early inthis century itwasfirst reported that restricted food intake canprolong life ofrodents bydecreasing theoccur- renceofspontaneous tumors (1,2).This finding wasgener- alized bystudies ofClive McCayandhisgroup(3, 4)inthe 1930s. These investigations havebeencritically reviewed by Harper (5), whopointed outthenecessity ofcareful useofthe termslongevity, life span,delayed disease onset, andlife expectation. Within thepast20years averitable explosion in publications relating nutrition tolongevity andemphasizing theroles played bydiet ininfluencing immunology, pathol- ogy,andendocrinology ofaging anddiseases ofaging inmice andrats hastaken place (6-12). Genetically short-lived mice regularly showearly thymic involution, early disorganization ofimmunological function, proneness todevelop relatively early inlife, hyalinizing renal diseases, vascular disease, deficiency anddisorganization ofimmune functions, autoim- munity, and,incertain strains, immunodeficiency anda variety ofmalignancies.