Laroque P, Keenan K P, Soper K A, Dorian C, Gerin G, Hoe C M, Duprat P
Laboratoires MSD-Chibret, Centre de Recherche, Clermont-Ferrand, France.
Exp Toxicol Pathol. 1997 Dec;49(6):459-65. doi: 10.1016/S0940-2993(97)80135-2.
The effects of ad libitum (AL) feeding, moderate dietary restriction (DR), and initial (6-week) and one-year body weights on the two-year survival of the Sprague-Dawley (SD) rat were evaluated. DR-fed rats were given approximately 75 percent of the adult AL food intake. At two years, body weights of DR-fed males and females were approximately 69 and 58 percent of the AL-fed male and female body weights, respectively. The 2-year survival rate was 80 and 74 percent in DR-fed males and females, respectively, and 28 and 38 percent in AL-fed males and females, respectively. This increase in longevity indicates that DR-fed males and females in carcinogenicity studies would have 14.8 and 9.1 additional weeks of exposure in a 2-year period to test compounds, respectively, compared to AL-fed animals. There was no correlation between initial body weight and 2-year survival in DR or AL-fed rats. There was no association between 1-year body weight and 2-year survival among DR-fed rats. However, AL-fed rats with the greatest 1-year body weight had a lower 2-year average survival compared with the lightest AL-fed rats; this trend was statistically significant only in males. Body weights between the first and second years were statistically significantly correlated for both genders and feeding regimens but no correlation was observed between pretest and 2-year body weights. These findings demonstrate that initial body weight is not the determining factor of 2-year survival, but that the total adult food (caloric) intake is important. In conclusion, moderate dietary restriction prevented excessive body weight gain and greatly increased the 2-year survival of the SD rat. Initial body weights did not correlate to 2-year body weight gain and were not a predictive biomarker of 2-year SD rat survival.
评估了随意进食（AL）、适度饮食限制（DR）以及初始（6周）和一年体重对Sprague-Dawley（SD）大鼠两年生存率的影响。饮食限制组的大鼠给予约为成年随意进食组食物摄入量75%的食物。两年时，饮食限制组雄性和雌性大鼠的体重分别约为随意进食组雄性和雌性大鼠体重的69%和58%。饮食限制组雄性和雌性大鼠的两年生存率分别为80%和74%，而随意进食组雄性和雌性大鼠的两年生存率分别为28%和38%。这种寿命的延长表明，在致癌性研究中，与随意进食组动物相比，饮食限制组雄性和雌性大鼠在两年期间分别有额外14.8周和9.1周的时间接触受试化合物。在饮食限制组或随意进食组大鼠中，初始体重与两年生存率之间没有相关性。在饮食限制组大鼠中，一年体重与两年生存率之间没有关联。然而，与体重最轻的随意进食组大鼠相比，一年体重最大的随意进食组大鼠的两年平均生存率较低；这种趋势仅在雄性中具有统计学意义。无论性别和喂养方式如何，第一年和第二年的体重在统计学上都具有显著相关性，但预试验体重与两年体重之间没有相关性。这些发现表明，初始体重不是两年生存率的决定因素，而成人总食物（热量）摄入量才是重要的。总之，适度饮食限制可防止体重过度增加，并大大提高SD大鼠的两年生存率。初始体重与两年体重增加无关，也不是SD大鼠两年生存率的预测生物标志物。
