Diet rich in soy proteins and one soybean component (e.g., phytoestrogens) have been reported to prevent cancer. The incidence of breast cancer in women and prostate cancer in men is much lower in the Far East than in North America and Europe. This difference is believed to be due mainly to the diet rather than to genetic (ethnic or "racial") differences because cancer risk increases greatly in Japanese who move to the United States and change from traditional (soybean rich) to western (soybean poor) diet. Studies in experimental animals suggest that genistein (i.e., a soy phytoestrogen) has anti-tumor activity. Three is also evidence that genistein can act as an antioxidant. This action could prolong life because oxygen-related damage to genes, cells, and organs is believed to be one of the main reasons why we age. Mice which have been genetically engineered to produce increased amounts of somatotropin (pituitary growth hormone, GH) do not live as long as normal mice. Animals from lines with high GH levels live approximately 1 year or even shorter, which is less than half of the life span of a normal mouse. We have shown that these animals have many signs of early aging of their brains and that in some of the lines we use, almost all females develop mammary tumors very early if life. Other investigators reported that most of these mice die from changes in the kidney which can be easily recognized by microscopic investigation and that they have increased levels of reactive oxygen compounds which may speed up their aging. We have recently shown that mutant mice unable to produce GH live much longer than their normal siblings. Most of them live at least 1 year longer than normals and a few live more than 4 years, which is a very old age for the mouse, corresponding to well over 100 years for the human. In these animals, tumors develop later in life, and their cells appear to have improved ability to "detoxify" reactive oxygen species. Data obtained in the short-living and long-living mice described above suggests that high levels of GH and large body size increase risk of cancer and other disease and accelerate aging. We are well aware that GH is being tested in elderly humans with the objective to improve body composition (to increase muscle and reduce fat) and to slow down deterioration of bones. We will feed normal, short-living (GH transgenic) and long-living (Ames dwarf) mice with the diets containing (i) no soy protein (casein), (ii) soy protein with low phytoestrogens, or (iii) soy protein with high phytoestrogens. The animals will be put on these diets at weaning. There will be 40 normal, 40 transgenic, and 40 dwarf mice in each group, half males and half females [(i.e., 20 animals per cell for 3 treatments at 8 levels (480 animals total)]. Survival and health of the animals will be monitored daily. Once a week, the animals will be weighed and carefully examined for evidence of mammary tumors or any other pathological changes. The animals that appear to be near death will be euthanized. These animals and the animals that died will be dissected and examined for incidence of grossly visible tumors and other lesions. The kidneys and organs in which tumors frequently develop (lungs, liver, and in females also mammary glands) will be removed, fixed, sectioned, and examined microscopically. We believe that the proposed studies will have two important outcomes. First of all, they will answer the question whether diet high in soybean components can prolong life in mice. The second important outcome of these studies relates specifically to the use of unique animal models we have characterized. If the diets in fact prolong life, by comparing the results obtained in normal, short-living and long-living mice, we will be able tentatively identify the mechanisms that may be involved. This will allow us to design further studies to determine what soybean diet does to make the animals live longer.
In this research, we will determine if eating a diet rich in soy protein/phytoestrogens will delay onset of age-related diseases and prolong life. To answer this question, we will use not only normal animals, but also two types of animals with altered genetic make-up which either die very early or live much longer than normal mice. We believe that using these novel and unique models of accelerated aging and delayed aging will give us a much better chance to explain how diet rich in soy protein may influence life expectancy.
