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[Cancer Research 59, 1642-1648, April 1, 1999]
© 1999 American Association for Cancer Research

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[Cancer Research 59, 1642-1648, April 1, 1999]
© 1999 American Association for Cancer Research


Tumor Biology

Dietary Intervention at Middle Age

Caloric Restriction but not Dehydroepiandrosterone Sulfate Increases Lifespan and Lifetime Cancer Incidence in Mice1

Thomas D. Pugh, Terry D. Oberley and Richard Weindruch2

Institute on Aging [T. D. P.] and Departments of Pathology and Laboratory Medicine [T. D. O.] and Medicine [R. W.], University of Wisconsin, Madison, Wisconsin 53706; and Pathology Service [T. D. O.] and the Geriatric Research, Education and Clinical Center [T. D. P., R. W.], Wm. S. Middleton Veterans Affairs Hospital, Madison, Wisconsin 53705.

Dietary manipulations to prevent cancer and other diseases of aging have drawn broad public and scientific attention. One indicator of this interest is that dehydroepiandrosterone (DHEA) supplements are widely consumed by those who hope that this hormone may keep them "younger longer." However, key data to support this belief are lacking. For example, the influence of DHEA treatment on spontaneous cancer and life span in healthy, long-lived strains of mice or rats is unknown. This is in contrast to the situation for caloric restriction (CR), which is known to oppose cancer development and increase maximum life span in rodents.

To address this issue, we assigned 300 middle age (12-month-old) male C57BL/6 mice to one of four groups (n = 75 for each group) and evaluated them for longevity and spontaneous disease patterns. Two groups were fed a normal diet (ND), and two others were fed a calorie-restricted diet (RD). One ND group and one RD group were also given 25 µg/ml DHEA sulfate (DHEAS) in their drinking water.

Although urine samples from DHEAS-treated mice contained 10-fold more DHEA and DHEAS than did samples from unsupplemented mice, DHEAS administration did not affect body weight, life span, or cancer patterns. The RD lowered body weight by 26% and increased maximum life span by ~15%. The incidence of the most prevalent cancer, plasma cell neoplasm, was higher in RD mice (66%) than in ND mice (41%).

Thus, DHEAS, as administered here, influenced neither cancer nor longevity at two caloric intakes. In contrast, CR from middle age increased longevity, the age at which tumor-bearing mice died, and the percentage of mice dying with cancers, suggesting that CR may retard promotion and/or progression of existing lymphoid cancers.




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Copyright © 1999 by the American Association for Cancer Research.