A Rational Basis for System Biology in the Aging-Associated Diseases: Are Genes or Protein Modifications the Upstream Cause?

A vast amount of research has been carried out to prepare system biology that could clarify the development of the aging-associated diseases, but a leading hypothesis is lacking. The data are prepared in primary cells, cell line cultures, knockout animals, chemical treatment, and chemical treatment of the knockout animals. Are genes or protein modifications responsible for the diseases? The upstream question needs a response before data can be accumulated to explain a mechanism of pathology. Data should be interactive in a system of biology. Proteins play an executive role in system biology, and small molecules regulate the network. In system biology, the interactions between proteins should be regulated according to a rule, but if a rule is different, the system biology is different. The data cannot be transferred from one system to another. The regulation of the protein network by the small molecules is impaired in transgenic cells. In systems biology, gene deletion or protein modification by the small molecules respectively disrupts or covalently modifies the signaling protein network of the Cam, and phosphatidylinoside -binding proteins. The systems biology, created by gene deletion and protein modification, are different. One cannot hope to recreate a system that leads to the diseases in aging based on an accumulation of data from different systems. Transgenic mice should be used only as a model of genetic disease, which leads to impairment of physiology in early infancy, but cannot be a model of drug development for the aging-associated diseases. In spite of their genetic differences, people are usually healthy in the first century of their life; the challenge is to understand the system biology that leads to the decline of health in aging.