Accelerated aging of giant transgenic mice is associated with elevated free radical processes

Transgenic growth hormone mice lived half as long as normal on a 23% protein diet. Longevities of both transgenic and control mice on a 38% protein diet were half those on 23% protein food. We hypothesized that transgenic mice are energetically constrained by their rapid growth, so energy supplements might improve "longevity assurance investments." As predicted, sucrose supplements extended the longevity of transgenic females (from a mean of 315 to 419 d). We measured two key biomarkers of aging (in brain, heart, liver, musculature, and kidneys) to test whether aging of these mice conformed to the free radical theory. Transgenic mice showed elevated levels of both superoxide radical (SOR) and lipid peroxidation (LP) compared with controls. The pattern of SOR and LP levels across kinds of mice and diets supported a free radical interpretation of aging and suggested that energy supply (protein or sugar) may impact longevity. The brain and heart were key biomarkers of longevity. LP levels in either organ explained 89% of the variation in longevity associated with genotype, sex, and diet. If combined with dietary restriction, this system should yield an 8-fold range in longevity, representing a powerful new tool for research into life histories and gerontology.