Mitochondrial theory of senescence: respiratory chain protein studies in human skeletal muscle.

In view of a previously demonstrated negative correlation between stage III respiratory activity in human mitochondria and increasing age, the relationship between human respiratory chain complex protein content and age was investigated. Quantitative immunoblot studies were carried out using holo complex I, III and IV antibody probes in human skeletal muscle mitochondrial homogenate from patients of varying ages. No significant negative correlation between increased age and respiratory complex chain protein content was seen for either total complex activity or for any of the subunits which could be reliably identified. As respiratory complex protein content is preserved with ageing, the decrease in respiratory efficiency is likely to follow aggregation of mutations in structural mitochondrial (mt) DNA genes which do not interfere with mt DNA transcription and protein translation rather than mutations in mt tRNA or ribosomal RNA genes. This is consistent with the fact that mt genes involved in protein translation only occupy a fairly small percentage of the mitochondrial genome.