Mitochondrial abnormalities in muscle and other aging cells: classification, causes, and effects.

The involvement of mitochondria and of mitochondrial DNA (mtDNA) in the aging process has generated much interest and even more controversy. The mitochondrial theory of aging considers a vicious circle consisting of: (1) accumulation of somatic mtDNA mutations; (2) impairment of respiratory chain function; (3) increased production of reactive oxygen species (ROS) in mitochondria; and (4) further damage to mtDNA. We review the evidence for and against the belief that these steps occur in aging muscle and brain, considering separately morphological, biochemical, and molecular data. The relationship between mitochondrial aging and late-onset neurodegenerative diseases is briefly reviewed. We conclude that mitochondrial dysfunction does play a crucial role in the aging process of both muscle and brain, but it remains unclear whether mitochondria are the culprits or mere accomplices. Copyright 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 000-000,