Victoria C Cogger, Nicholas J. Hunt, Glen Lockwood, David G. Le Couteur

Centre for Education Research on Ageing, University of Sydney

 

There is an exponential increase in most diseases with old age, and consequently ageing is established as the most significant risk factor for disease. Novel therapeutic approaches that target the biological changes of ageing have been increasingly advocated, for example by research leaders at the National Institutes of Health and in research publications such as Cell, Science and Nature Medicine.

Approximately three quarters of people over 75 years have diabetes or pre-diabetes and/or hyperlipidaemia. These are established risk factors for cardiovascular outcomes, and are now recognized as risk factors for geriatric conditions such as dementia, sarcopenia, frailty and osteoporosis. With the liver as the key driver of lipid metabolism and the action of insulin we have focused our research on age-related liver changes that may detrimentally impact these events leading to increased diseases susceptibility. Our research has demonstrated changes in the liver microcirculation that impair lipid and insulin delivery to the hepatocytes leading to dyslipidemia and insulin resistance. This discovery has uncovered new mechanisms for the regulation of key features of the liver microcirculation and delivered new therapeutic options. Recently we have shown that it is possible to target the microcirculatory changes with nanomedicines by harnessing the extremely efficient endocytotic capacity of the liver sinusoid endothelium. We are now undertaking proof-of-principle testing of a range of pharmacotherapeutic agents using nanomedicine carriers for cargo delivery of specific drugs that regulate the liver microcirculation and propose that this will help to prevent and treat risk factors for age-related disease.