Bn. Blackwell et al., LONGEVITY, BODY-WEIGHT, AND NEOPLASIA IN AD LIBITUM-FED AND DIET-RESTRICTED C57BL6 MICE FED NIH-31 OPEN FORMULA DIET, Toxicologic pathology, 23(5), 1995, pp. 570-582
Groups of C57BL6 mice of each sex were assigned to one of 2 dietary re
gimens, ad libitum (AL) or dietary restriction (DR), to study effects
of food restriction on body weight, survival, and neoplasia. The AL an
d DR groups were subdivided into a scheduled sacrifice group for exami
nation at 6-mo intervals, and a lifetime group to provide longevity da
ta. Necropsies and microscopic examinations were conducted on 911 anim
als. In the lifetime group food consumption averaged 33.6 and 34.4 g p
er week by AL males and AL females, respectively; the DR counterparts
were given 40% less. The diet contained 4.35 kcal/g. The average lifet
ime body weights were 34.8, 26.8, 22.6, and 21.6 g for AL males, AL fe
males, DR males, and DR females, respectively, and their age at 50% su
rvival was 27.5, 26.9, 31.7, and 33.5 mo. Maximal lifespan was increas
ed 18% in DR males and females. Lifetime incidence of tumor-bearing mi
ce was 89% and 86% for AL males and females, versus 64% for each sex o
f DR mice. Dramatic reduction occurred in female DR mice in lymphoma (
9% vs 29%), pituitary neoplasms (1% vs 37%), and thyroid neoplasms (0.
4% vs 8%). In males, hepatocellular tumors were reduced to 1% from 10%
by DR. In contrast, the incidence of histiocytic sarcoma was increase
d in DR females and unaffected in DR males. Tumor onset was delayed in
DR animals; 87% of all neoplasms in males and 95% in females had occu
rred in the AL mice by 24 mo, whereas the DR animals had only 52% and
39% of their lifetime incidence, respectively, by that age. This study
provided comparative AL and DR data from C57BL6 mice examined randoml
y at 6-mo intervals (cross-sectional group) in parallel with data from
animals in similar cohort that was unsampled and allowed to succumb n
aturally (longevity group). Dietary restriction reduced the lifetime p
ercentage of tumor-bearing animals and the number of tumors per animal
, and delayed the age at onset of most neoplasms.