The presence of COX-negative fibers can be indicative of several underlying conditions. These may include mitochondrial myopathies, aging, chronic diseases, or genetic mutations affecting mitochondrial DNA. In mitochondrial myopathies, mutations in mitochondrial DNA or nuclear DNA that encode mitochondrial proteins may lead to defective COX activity. Aging-related sarcopenia can also present with an increased number of COX-negative fibers due to the accumulation of mitochondrial DNA mutations over time.
