Abstract

Aging is one of the inevitable aspects of life, affecting homeostatic states of every physiological system including that of hemostasis. Through systematic transgenic studies of age-related dynamic changes in expression of genes for hemostatic factors, we found the very first molecular mechanism of age-related homeostasis, the ASE/AIE-mediated genetic mechanism for age-related regulation of gene expression. In this mechanism, together with other essential elements for the promoter activity, two genetic elements—age-related stability element (ASE) and age-related increase element (AIE)—play critical roles, producing four age-related gene expression patterns. This mechanism is also found to be the first puberty-onset gene switch mechanism identified. This ASE/AIE-mediated regulatory mechanism has universal functionality across different genes and animal species. In addition to the age-related regulatory activity, ASE also has a unique tissue-specificity regulatory activity. Global analyses of lifetime age-related expression profiles of mouse liver genes and proteins were carried out, and the results support that there exists a small number of fundamental age-related regulatory mechanisms of genes and proteins that govern complex age-related homeostatic regulations. A large body of information obtained from the global analyses has been constructed into a versatile database, which is a platform resource for studying age-related homeostasis.

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