Approved Research

The role of somatic and inherited mitochondrial genetic variation in biological ageing and disease.

Lay summary

Mitochondria are organelles found in almost every cell type in the human body. Mitochondria are vital, they help convert the energy in the food we consume into energy that can be used by cells to carry out their functions. They do this through the production of Adenosine Triphosphate (ATP). As well as energy production, they are involved in signalling between cells and programmed cell death. As we age, mitochondrial function begins to decline. When mitochondria stop doing their job correctly, age-related diseases such as Alzheimer's disease, Parkinson's disease, and cancer can arise. Often the reason for dysfunction in mitochondria is due to slight variation in the mitochondrial DNA. Mitochondrial DNA is more prone to damage than the DNA found in the nucleus of the cell. This is because during the synthesis of ATP, free radicals are produced that cause damage to the mitochondrial DNA. Mitochondria also lack the same mechanisms that protect the DNA in the nucleus of the cell. However, most mitochondrial diseases occur due to mutations in nuclear DNA that affect components that make up the mitochondria. These mutations can either be inherited or spontaneous.

This PhD project will last approximately four years and use computational analyses to identify mutations that are shared among many people and may explain how diseases arise that grow more common as we age. We will study both variations in mitochondrial DNA itself and in nuclear genes that are responsible for encoding mitochondrial proteins. We will also study the association between age-related chronic disease and certain genetic phenomena such as segments of mitochondrial DNA being inserted into the nuclear genome (NUMT analyses) and the degradation of proteins that protect chromosomes from damage (telomere length analyses).

Human life expectancy has increased greatly over recent decades. With age, comes chronic age-related disease. The genetic basis of many of these diseases is still poorly understood and few effective treatments exist for age-related neurodegenerative diseases and the later years of life are often spent in poor health. In order to address the rising incidence of chronic diseases, disability, and economic dependency among the elderly, we must reduce detrimental ageing and morbidity. We hope to utilise the large amount of data available from UK Biobank to help advance our understanding of these diseases which will in turn improve the treatments elderly patients receive and help alleviate the socioeconomic burden on global healthcare systems to care for ageing patients.