The effects of overfeeding and dietary restriction on Sprague-Dawley rat survival and early pathology biomarkers of aging.
A significant correlation exists between average daily food consumption and 2-yr survival in control ad libitum (AL)-fed Sprague-Dawley (SD) rats. SD rats were fed Purina Rodent Chow 5002 or a modified chow, 5002-9, with lower protein, fat, metabolizable energy and increased fiber AL or by dietary restriction (DR) to 65% of the AL amount by measurement or time (6.5 hr). At 52 wk, food consumption and key pathology biomarkers correlated with 106-wk survival. The modified chow, 5002-9 fed AL, did not significantly improve survival. SD rats fed either diet AL consumed the greatest amount of feed and kcal/rat but consumed the same amount of feed per gram body weight as DR-fed rats. At 52 wk, AL rats fed either diet had the same brain weights as DR rats, but the AL-fed rats had greater body weight and body fat content and increased heart, lung, kidney, liver, adrenal, thyroid, and pituitary weights as well as an increased incidence and severity of degenerative and/or proliferative lesions in these organs. This study demonstrates that overfeeding best correlates with low 2-yr survival in SD rats and that simple DR by caloric restriction modifies key pathology biomarkers in the pituitary, mammary gland, kidney, and heart of SD rats at 52 wk that are predictive of 106-wk survival.
Keenan
K P
KP
Department of Safety Assessment, Merck Research Laboratories, West Point, Pennsylvania 19486.
Smith
P F
PF
Hertzog
P
P
Soper
K
K
Ballam
G C
GC
Clark
R L
RL
D000375:Aging / Q000502:physiology; D000821:Animal Feed; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D004435:Eating / Q000502:physiology; D005260:Female; D005508:Food Deprivation / Q000502:physiology; D008136:Longevity / Q000502:physiology; D008297:Male; D009929:Organ Size / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000502:physiology*