Evidence for and against the causal involvement of mitochondrial DNA mutation in mammalian ageing.

ABSTRACT

Current experimental evidence on the role of mitochondrial DNA mutation in ageing is assessed alongside reports implicating other genetic and non-genetic causes, including inter-relationships between the mitochondrial and nuclear genomes and their potential effect on mitochondrial structure and function. The role of a 5-kb mtDNA deletion, identified as age-dependent in a variety of human and other mammalian species, is specifically evaluated in the context of its functional effect in mitotic and non-mitotic adult tissue. Downstream effects of mitochondrial decline are considered in terms of the maintenance of ATP production. Associated sequelae then are discussed specifically with reference to restrictions in the supply of ribose moieties for DNA and RNA synthesis, and to disruption of NADPH production and hence cellular anti-oxidant defences.