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Aging and Food Restriction Alter Some Indices of Bone Metabolism in Male Rhesus Monkeys (Macaca mulatta)^1,2,

Mark A. Lane³, Abraham Z. Reznick^*, Edward M. Tilmont, A. Lanir^*, Sheldon S. Ball, Virginia Read, Donald K. Ingram, Richard G. Cutler and George S. Roth

Molecular Physiology and Genetics Section, Nathan Shock Laboratories, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Hopkins Bayview Medical Center, Baltimore, MD 21224 ^* Technicon-Israel Institute of Technology, The Faculty of Medicine, Department of Morphological Sciences, Rappaport Building, Haifa, Israel 31086 Department of Pathology, The University of Mississippi, School of Medicine, Jackson, MS 39216

Food restriction increases life span, reduces aging rate and affects a wide variety of biological functions. In rats, food restriction delays bone growth and reduces bone density and mineral content. We report the effects of aging and long-term (>6.0 y) food restriction on several indices of bone growth and metabolism in rhesus monkeys (Macaca mulatta). Food allotments for controls approximated free access consumption, whereas food-restricted monkeys received 30% less food on a body weight basis. Cross-sectional and longitudinal age effects on serum alkaline phosphatase paralleled those reported for humans. Food restriction induced a significant delay in the developmental decline (to adult levels) in total alkaline phosphatase and significantly suppressed serum interleukin 6 concentrations, particularly in younger monkeys. Also, food restriction slowed skeletal growth, as reflected by shorter crown-rump length, and significantly reduced total body bone mineral content, but not bone mineral density, measured by dual energy X-ray absorptiometry. Analyses of serum parathyroid hormone, calcium, phosphate and osteocalcin concentrations suggested that the effects on skeletal growth were not related to alterations in calcium and phosphate homeostasis or a primary defect in bone formation. These findings suggest that long-term food restriction delays skeletal development in male rhesus monkeys while allowing the development of a reduced but otherwise normal skeleton.

KEY WORDS: • dietary restriction • bone metabolism • Macaca mulatta • aging • dual energy X-ray absorptiometry

¹ Portions of this work have been presented previously [Lane, M. A., Baer, D. J., Rumpler, W. V., Tilmont, E. M., Ingram, D. K., Cutler, R. G. & Roth, G. S. (1993) Long-term diet restriction in nonhuman primates: the NIA study. FASEB J. 7: A820 (abs.)].

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ To whom correspondence should be addressed.

Manuscript received 29 August 1994. Revision accepted 29 November 1994.

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