|
Sign In to gain access to subscriptions and/or personal tools.
|
The Effects of Overfeeding and Dietary Restriction on Sprague-Dawley Rat Survival and Early Pathology Biomarkers of Aging
Kevin P. Keenan
Departments of Safety Assessment and Biometrics, Merck Research Laboratories, West Point, Pennsylvania 19486, and Purina Mills, Inc., St. Louis, Missouri
Peter F. Smith
Departments of Safety Assessment and Biometrics, Merck Research Laboratories, West Point, Pennsylvania 19486, and Purina Mills, Inc., St. Louis, Missouri
Phillip Hertzog
Departments of Safety Assessment and Biometrics, Merck Research Laboratories, West Point, Pennsylvania 19486, and Purina Mills, Inc., St. Louis, Missouri
Keith Soper
Departments of Safety Assessment and Biometrics, Merck Research Laboratories, West Point, Pennsylvania 19486, and Purina Mills, Inc., St. Louis, Missouri
Gordon C. Ballam
Departments of Safety Assessment and Biometrics, Merck Research Laboratories, West Point, Pennsylvania 19486, and Purina Mills, Inc., St. Louis, Missouri
Robert L. Clark
Departments of Safety Assessment and Biometrics, Merck Research Laboratories, West Point, Pennsylvania 19486, and Purina Mills, Inc., St. Louis, Missouri
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.
Key Words: Caloric restriction • cell proliferation • bromodeoxyuridine labeling • pituitary hyperplasia • neoplasia • nephropathy • cardiomyopathy
Toxicologic Pathology, Vol. 22, No. 3,
300-315 (1994)
DOI: 10.1177/019262339402200308
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
S. D. Seidel, S.-C. Hung, H Lynn Kan, and B Bhaskar Gollapudi
Background Gene Expression in Rat Kidney: Influence of Strain, Gender, and Diet
Toxicol. Sci.,
November 1, 2006;
94(1):
226 - 233.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. P. Keenan, C.-M. Hoe, L. Mixson, C. L. Mccoy, J. B. Coleman, B. A. Mattson, G. A. Ballam, L. A. Gumprecht, and K. A. Soper
Diabesity: A Polygenic Model of Dietary-Induced Obesity from Ad Libitum Overfeeding of Sprague-Dawley Rats and Its Modulation by Moderate and Marked Dietary Restriction
Toxicol Pathol,
October 1, 2005;
33(6):
650 - 674.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Molon-Noblot, M.-F. Hubert, C.-M. Hoe, K. Keenan, and P. Laroque
The Effects of Ad Libitum Feeding and Marked Dietary Restriction on Spontaneous Skeletal Muscle Pathology in Sprague-Dawley Rats
Toxicol Pathol,
August 1, 2005;
33(5):
600 - 608.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Molon-Noblot, P. Laroque, J. B. Coleman, C.-M. Hoe, and K. P. Keenan
The Effects of Ad Libitum Overfeeding and Moderate and Marked Dietary Restriction on Age-Related Spontaneous Pituitary Gland Pathology in Sprague--Dawley Rats
Toxicol Pathol,
April 1, 2003;
31(3):
310 - 320.
[Abstract]
[PDF]
|
|
|
|
|
|
|
P. H. Duffy, S. M. Lewis, M. A. Mayhugh, A. McCracken, B. T. Thorn, P. G. Reeves, S. A. Blakely, D. A. Casciano, and R. J. Feuers
Effect of the AIN-93M Purified Diet and Dietary Restriction on Survival in Sprague-Dawley Rats: Implications for Chronic Studies
J. Nutr.,
January 1, 2002;
132(1):
101 - 107.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Molon-Noblot, K. P. Keenan, J. B. Coleman, C.-M. Hoe, and P. Laroque
The Effects of Ad Libitum Overfeeding and Moderate and Marked Dietary Restriction on Age-Related Spontaneous Pancreatic Islet Pathology in Sprague--Dawley Rats
Toxicol Pathol,
April 1, 2001;
29(3):
353 - 362.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. W. Lawrence, G. K. Wollenberg, and J. G. DeLuca
Tumor necrosis factor {{alpha}} is not required for WY14,643-induced cell proliferation
Carcinogenesis,
March 1, 2001;
22(3):
381 - 386.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. P. Keenan, J. B. Coleman, C. L. Mccoy, C.-M. Hoe, K. A. Soper, and P. Laroque
Chronic Nephropathy in Ad Libitum Overfed Sprague-Dawley Rats and Its Early Attenuation by Increasing Degrees of Dietary (Caloric) Restriction to Control Growth
Toxicol Pathol,
November 1, 2000;
28(6):
788 - 798.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M.-F. Hubert, P. Laroque, J.-P. Gillet, and K. P. Keenan
The Effects of Diet, ad Libitum Feeding, and Moderate and Severe Dietary Restriction on Body Weight, Survival, Clinical Pathology Parameters, and Cause of Death in Control Sprague-Dawley Rats
Toxicol. Sci.,
November 1, 2000;
58(1):
195 - 207.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. TEILLET, P. VERBEKE, S. GOURAUD, H. BAKALA, C. BOROT-LALOI, D. HEUDES, P. BRUNEVAL, and B. CORMAN
Food Restriction Prevents Advanced Glycation End Product Accumulation and Retards Kidney Aging in Lean Rats
J. Am. Soc. Nephrol.,
August 1, 2000;
11(8):
1488 - 1497.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
K P Keenan
BSELLE newsletter commentary: does caloric restriction induce hormesis?
Human and Experimental Toxicology,
June 1, 2000;
19(6):
335 - 337.
[PDF]
|
|
|
|
|
|
|
M. Kemi, K. P. Keenan, C. Mccoy, C.-M. Hoe, K. A. Soper, G. C. Ballam, and M. J. Van Zwieten
The Relative Protective Effects of Moderate Dietary Restriction versus Dietary Modification on Spontaneous Cardiomyopathy in Male Sprague-Dawley Rats
Toxicol Pathol,
March 1, 2000;
28(2):
285 - 296.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. K. Haseman, J. R. Hailey, and R. W. Morris
Spontaneous Neoplasm Incidences in Fischer 344 Rats and B6C3F1 Mice in Two-Year Carcinogenicity Studies: A National Toxicology Program Update
Toxicol Pathol,
May 1, 1998;
26(3):
428 - 441.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. E. A. Leakey, J. E. Seng, C. R. Barnas, V. M. Baker, and R. W. Hart
A Mechanistic Basis for the Beneficial Effects of Caloric Restriction On Longevity and Disease: Consequences for the Interpretation of Rodent Toxicity Studies
International Journal of Toxicology,
January 1, 1998;
17(2_suppl):
5 - 56.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. Turturro, B. Hass, R. Hart, and W. T. Allaben
Body Weight Impact On Spontaneous Diseases in Chronic Bioassays
International Journal of Toxicology,
January 1, 1998;
17(2_suppl):
79 - 99.
[Abstract]
[PDF]
|
|
|
|
|
|
|
K. P Keenan
Effects of Diet and Overfeeding On Body Weight and Survival in the Rodent Bioassay: the Impact On Pharmaceutical Safety Assessment
International Journal of Toxicology,
January 1, 1998;
17(2_suppl):
101 - 117.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. K. Haseman
National Toxicology Program Experience With Dietary Restriction: Does the Manner in Which Reduced Body Weight Is Achieved Affect Tumor Incidence?
International Journal of Toxicology,
January 1, 1998;
17(2_suppl):
119 - 134.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. K. Haseman, G. A. Boorman, and J. Huff
Value of Historical Control Data and Other Issues Related to the Evaluation of Long-Term Rodent Carcinogenicity Studies
Toxicol Pathol,
September 1, 1997;
25(5):
524 - 527.
[PDF]
|
|
|
|
|
|
|
J. K. Haseman, E. Young, S. L. Eustis, and J. R. Hailey
Body Weight-Tumor Incidence Correlations in Long-Term Rodent Carcinogenicity Studies
Toxicol Pathol,
May 1, 1997;
25(3):
256 - 263.
[Abstract]
[PDF]
|
|
|
|
|
|
|
K. P. Keenan, G. C. Ballam, R. Dixit, K. A. Soper, P. Laroque, B. A. Mattson, S. P. Adams, and J. B. Coleman
The Effects of Diet, Overfeeding and Moderate Dietary Restriction on Sprague-Dawley Rat Survival, Disease and Toxicology
J. Nutr.,
May 1, 1997;
127
(5):
851S - 851S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. P Keenan, P. Laroque, G. C. Ballam, K. A. Soper, R. Dixit, B. A. Mattson, S. P Adams, and J. B. Coleman
The Effects of Diet, Ad Libitum Overfeeding, and Moderate Dietary Restriction on the Rodent Bioassay: The Uncontrolled Variable in Safety Assessment
Toxicol Pathol,
November 1, 1996;
24(6):
757 - 768.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. Turturro, P. Duffy, R. Hart, and W. T. Allaben
Rationale for the Use of Dietary Control in Toxicity Studies--B6C3F1 Mouse
Toxicol Pathol,
November 1, 1996;
24(6):
769 - 775.
[Abstract]
[PDF]
|
|
|
|
|
|
|
W. T. Allaben, A. Turturro, J. E.A. Leakey, J. E. Seng, and R. W. Hart
FDA Points-to-Consider Documents: The Need for Dietary Control for the Reduction of Experimental Variability within Animal Assays and the Use of Dietary Restriction to Achieve Dietary Control
Toxicol Pathol,
November 1, 1996;
24(6):
776 - 781.
[Abstract]
[PDF]
|
|
|
|
|
|
|
K. P. Keenan
Commentary: The Uncontrolled Variable in Risk Assessment: Ad Libitum Overfed Rodents-Fat, Facts and Fiction
Toxicol Pathol,
May 1, 1996;
24(3):
376 - 383.
[PDF]
|
|
|
|
|
|
|
K. P. Keenan, K. A. Soper, P. F. Smith, G. C. Ballam, and R. L. Clark
Diet, Overfeeding, and Moderate Dietary Restriction in Control Sprague-Dawley Rats: I. Effects on Spontaneous Neoplasms
Toxicol Pathol,
May 1, 1995;
23(3):
269 - 286.
[Abstract]
[PDF]
|
|
|
|
|
|
|
K. P. Keenan, K. A. Soper, P. R. Hertzog, L. A. Gumprecht, P. F. Smith, B. A. Mattson, G. C. Ballam, and R. L. Clark
Diet, Overfeeding, and Moderate Dietary Restriction in Control Sprague-Dawley Rats: II. Effects on Age-Related Proliferative and Degenerative Lesions
Toxicol Pathol,
May 1, 1995;
23(3):
287 - 302.
[Abstract]
[PDF]
|
|
|
|
|
