A multitude of human diseases (e.g., thrombosis, cardiovascular diseases, diabetes, Alzheimer's disease, cancer, osteoporosis, osteoarthritis, Parkinson's disease, dementia) are associated with increasing age and result in serious effects on the quality of life and on the life expectancy of individuals suffering from such diseases. Other diseases (e.g., cirrhosis, primary and metastatic neoplasia, Wilson disease, hepachromatosis, infectious hepatitis, hepatic necrosis, Gilbert disease, Criggler-Najar disease) which afflict the liver also have serious clinical manifestations and are responsible for high morbidity and mortality.
The treatment of age-related diseases (i.e., diseases whose prevalence and/or severity of clinical manifestations increases with the age of the patient) and diseases afflicting the liver focuses on the alleviation of the general symptoms of the disease using one or a combination of two modalities, i.e., non-pharmacological treatment and pharmacological treatment. Non-pharmacological treatment include, for example, periods of bed rest and dietary changes. Non-pharmacological treatment is often used as an adjunct to pharmacological treatment which involves the use of drugs. Unfortunately, many of the commonly used pharmacological agents have numerous side effects and their use is further exacerbated by the non-responsiveness by many patients with severe disease, who, paradoxically, are in most need of treatment. Both non-pharmacological and pharmacological treatments provide unsatisfactory approaches to treating age-related and liver-associated diseases because these approaches are often ineffective, their effects are inconsistent, and are directed to alleviating the general symptoms of disease, rather than to specifically addressing the source of morbidity and mortality. Moreover, no suitable animal models are currently available to rationally design drugs which target specific biochemical and physiological pathways which are associated with age-related and with liver-associated diseases.
What is needed are methods for age-related and liver-specific gene expression and models for age-related and liver-specific diseases.