Dietary intervention at middle age: Caloric restriction but not dehydroepiandrosterone sulfate increases lifespan and lifetime cancer incidence in mice

Dietary manipulations to prevent cancer and other diseases of aging have dr awn broad public and scientific attention, One indicator of this interest i s that dehydroepiandrosterone (DHEA) supplements are widely consumed by tho se who hope that this hormone mag 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 strai ns of mice or rats is unknown. This is in contrast to the situation for cal oric restriction (CR), which is known to oppose canter development and incr ease maximum lift span in rodents. To address this issue, we assigned 300 middle age (12-month-old) malt C57BL /6 mice to one of four groups (n = 75 for each group) and evaluated them fo r longevity and spontaneous disease patterns. Two groups were fed a normal diet (ND), and two others were fed a caloric-restricted diet (RD), One ND g roup and one RD group were also given 25 mu g/ml DHEA sulfate (DHEAS) in th eir drinking water. Although urine samples from DHEAS-treated mice contained 10-fold more DHEA and DHEAS than did samples from unsupplemented mice, DHEAS administration d id not affect body weight, life span, or cancer patterns. The RD lowered bo dy weight by 26% and increased maximum life span by similar to 15%. The inc idence 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 dyin g with cancers, suggesting that CR may retard promotion and/or progression of existing lymphoid cancers.