When we age, we have numerous reduced, or even loss of, bodily functions. The liver is no exception - despite being one of the most robust organs in the body, the liver also ages. One such age-affected function is the communication between the blood and the liver's major cells, the hepatocytes. In this qualification project we will optimize our approach towards reversing age-related changes in liver sinusoidal endothelial cells (LSEC) which form the physical border between the blood and the hepatocytes, and line the 1 billion blood vessels permeating the liver. So, with ageing, the most dramatic age-related liver changes are within the LSEC, where LSEC become thicker and lose their porosity. The purpose of this project is therefore to test newly invented drugs and new drug formulations on LSEC, to determine if they can reverse ageing effects in LSEC. Initial pilot studies are very encouraging - using these new drugs we can restore lost porosity in LSEC from old mice. In this qualification project we therefore intend to optimise the drugs and drug formulations to further improve their ability to reverse such age-related changes in the liver.
We propose that our strategy to maintain fenestration porosity into old age with our PACA-pill therapy will ameliorate age-related dyslipidemia and insulin resistance, and provide new means for preventing cardiovascular/microvascular/metabolic disease in older people. PACA-pill will improve our health-span and thus our quality of life as we age, and provide employment opportunities in pharma industries in Norway and Europe. PACA-Pill ultimately entails the development of a novel therapy for an entirely novel therapeutic target, and has the potential to increase the health-span/life-quality of ageing populations, a current major societal challenge. Improving health-span has multiple benefits for the individual and society in general. In this project we have successfully achieved the incorporation of agents into PACA-pill vectors and these will be tested for therapeutic benefit in the near future.