Abstract

Mitochondria are well known as “powerhouses” of our cells. Their vital function is absolutely dependent on a tiny DNA molecule residing inside them – a mitochondrial genome. Each cell contains multiple copies of mitochondrial genome, from hundreds to millions. A rich literature shows progressive accumulation of mutations in mitochondrial genome with age and implicates this accumulation in numerous age-related conditions such sarcopenia and diabetes mellitus. In our project we aim to understand the mechanisms underlying spread of mutant mitochondrial genomes in somatic tissues and test significance of their accumulation in causing aging symptoms. We focus on mouse skeletal muscle fibers as they are notorious for accumulation of mutant mitochondrial genomes with age which has a clinical manifestation as ragged red fibers. We are using a multidisciplinary approach, combining cutting-edge technologies such as single cells sequencing with development of unique methods for mitochondrial genome transplantation. Ultimately, this project will bring new insights into the mechanisms underlying mitochondrial genome deterioration in mammalian somatic tissues with age and guide efforts in maintaining its integrity to hopefully extend human health-span.