FAT, FRAIL AND DYING YOUNG - SURVIVAL, BODY-WEIGHT AND PATHOLOGY OF THE CHARLES RIVER SPRAGUE-DAWLEY-DERIVED RAT PRIOR TO AND SINCE THE INTRODUCTION OF THE VAFR VARIANT IN 1988

Trends in survival and body weight were evaluated in 2140 control Sprague-Dawley-derived [Crl: COBS-CD(SD)BR and Crl: COBS-VAF CD(SD)BR] rats used for 24-month rat carcinogenicity studies between 1979 and 1991. Body weight and survival were remarkably stable in the CD-COBS rats used during 1979-1987: at 24 months, the mean survival in males was 68 +/- 5%, and 60 +/- 5% in females. With the CD-COBS-VAF rat, a variant of the CD-COBS strain used between 1988 and 1991, the survival at 24 months dropped to 41 +/- 3% in males, and 44 +/- 7% in females compared to the CD-COBS, The CD-COBS-VAF rat had a significantly reduced life span (P<0.001 at 24 months), a significant increase in mean body weight (males at 6 months: 672 +/- 24 g vs. 536 +/- 6 g; females: 359 +/- 7 g vs 308 +/- 3 g; P<0.001) and food consumption (males at 6 months: 31.3 +/- 3.3 vs. 25.4 +/- 2.1 g d-1 ; females: 22.0 +/- 2.7 g v. 20.3 +/- 2.0 g d-1 ; P<0.001). CD-COBS-VAF rats which failed to survive up to study termination had individual body weights at 3, 6 and 12 months which were significantly higher (P<0.001) than those which survived until 24 months, Our historical data base of control rats (CD-COBS and CD-COBS-VAF) in carcinogenicity studies revealed a significant (males:P<0.001; females:P<0.01) and inverse linear relation between mean 3-month body weight and 24 month survival. When compared to CD-COBS animals, CD-COBS-VAF rats showed an increase in the incidence of pituitary tumours in males, mammary fibroadenomas in females, an increase in the incidence and severity of glomerulonephrosis, and a greater incidence of animals which died without any obvious pathology. It is concluded that, in our Sprague-Dawley substrains, both the individual and th group mean body weights in early adult life appear predictive for the individual and group life expectancy. The decrease in longevity in the CD-COBS-VAF rat is principally due to disease and degeneration processes associated with fast growth and high body weight,