Muscle function as a mediator of ageing phenotype in people living with HIV: a basis for stratified intervention
HIV is now a chronic manageable condition, but health span is less well preserved than lifespan. People living with HIV (PLWH) present a valuable model in which to study the interplay of biological pathways of ageing (mitochondrial dysfunction, chronic inflammation), convergent ageing phenotypes (frailty, sarcopenia), and specific diseases of older age, as all these are increased in PLWH. We now need to better define these relationships in order to trial targeted interventions.
One new way of tackling this problem would be to target the premature ageing process itself. In this way, we can hope to target specific treatments to different groups of older HIV positive people based on how the ageing process is affecting them. The aim of my project is to try to find a way to do this.
I will be performing a range of experiments, comparing HIV positive people over 50 years old with HIV negative people of a similar age. The participants come for a study visit where we take samples (blood, urine, and a small piece of muscle from the leg). They also do simple physical tests that are known to be affected by the ageing process. We will then match up signs of ageing in the whole person (such as frailty), with signs of ageing that we can measure in the lab. In this way, we hope to identify groups of HIV positive people that are ageing better than others. If we can discover what these different groups are, we will be able to plan future studies which offer them more targeted treatments to increase healthy ageing.
This will be the first project to encompass wide ranging studies on both molecular and clinical biology in older HIV positive patients. It will hopefully be the framework for interventional trials in the future which look to improve the age-related health of HIV positive people.
- Immunohistochemical analyses of muscle biopsies
- Molecular analyses of muscle biopsies
- Epidemiological analyses
- Development of proposed phenotypic subgroups