Potential for a future drug therapy for NAFLD in older adults?
Most of the risk factors for NAFLD are within our control. For example, high cholesterol, high blood pressure, obesity, smoking and a sedentary lifestyle can all be addressed by eating a healthy diet, quitting smoking and doing adequate and regular exercise. However, our increasing age is out with our control and NAFLD is more common in adults aged over 50. Ageing appears to increase the risk of fatty liver via different mechanisms such as oxidative stress and fat tissue dysfunction.
As we age, senescent (or old) cells build up in our tissues. Senescence is the process by which cells irreversibly stop dividing and enter a state of permanent growth cessation without undergoing cell death. Although these senescent cells can no longer replicate, they remain metabolically active and often become pro-inflammatory and can negatively impact age-related conditions such as NAFLD. In the liver, these senescent cells store excessive fat as they cannot effectively use the fat as fuel, so end up storing it. Removing these senescence cells from the liver could help increase resistance against the development of NAFLD in older adults.
Researchers from the University of Newcastle’s Institute for Ageing have recently conducted work exploring the mechanisms which cause a build-up of fat in the liver. They also investigated two methods used to eliminate the senescent cells in the liver, which allows them to be replaced by young cells. One method was to firstly use a genetically engineered mouse model in which the senescent cells could be ‘killed off’. The second method used a treatment with a combination of drugs known to specifically ‘kill off’ senescent cells. The results were equally successful in reducing the build-up of fat in the liver of the ageing mice used in the study.
The research in this area is still at a very early stage. The studies by the researchers at the University of Newcastle was conducted in mice, and more research is needed to increase our understanding of potential methods to eliminate the senescent cells without causing any detrimental side effects. It is an exciting area of research that could potentially lead to the development of a clinical treatment to reduce the build-up of fat in the liver.
Currently, there is no effective drug therapy for treating NAFLD. Diet and lifestyle modifications remain the main prevention and treatment options. Eating a healthy, varied diet and having a healthy body weight, keeping active, not smoking and cutting down or not drinking alcohol are all likely to reduce the risk of NAFLD.
For more information on the research referred above see: http://www.ncl.ac.uk/press/news/2017/06/fattyliverdiseasereversed/