Researchers here demonstrate an association between reduced mitochondrial function and onset of sarcopenia in nematode worms. Muscle tissue requires a lot of energy for function and maintenance, and that energy is supplied in the form of adenosine triphosphate (ATP) by the roving herds of mitochondria found within muscle cells. Progressive failure of mitochondrial function is a feature of aging, and is thought to be a contributing cause of the loss of muscle mass and strength, known as sarcopenia, that is characteristic of late life physiology.
Sarcopenia is not exclusive to humans, and has been observed in non-human primates, dogs, rodents, and even the microscopic worm, C. elegans. These observations, therefore, suggest that sarcopenia is an evolutionarily conserved process and whilst some evidence suggests the underlying mechanisms might also be conserved, it remains an open question. There are several theories regarding the cause of sarcopenia, but we do not yet fully understand its aetiology, not least because of an absence of life-long, prospective studies.
Muscle architecture is highly conserved between C. elegans and mammals and the major signaling pathways and degradation systems are also present in both system. Thus, C. elegans is a good organism in which to investigate the molecular changes to muscle with ageing. Previous studies have shown that ageing in C. elegans muscle is characterized by altered structure and reduced function. This is displayed as progressive disorganization of sarcomeres and reduced cell size. Alterations to sarcomere structure have been associated with changes to locomotive ability. Alongside changes to muscle structure and function, mitochondrial defects such as increased fragmentation and reduced mitochondrial volume have also been observed in the body wall muscles of aged C. elegans.
Recently large scale studies using RNAi have been conducted to investigate how muscle health is maintained in C. elegans. These studies have examined the effect of knocking down more than 850 genes on sub-cellular muscle architecture. The results highlighted that in control animals sub-cellular components remained normal through early adulthood, however, after day three of adulthood, abnormal sarcomere and mitochondrial structures were observed. Furthermore, mitochondrial fragmentation appeared to arise earlier in the ageing process than the alterations to sarcomere structure. These data suggest that mitochondrial abnormalities precede other changes to muscles with age.
Here, we use C. elegans natural scaling of lifespan in response to temperature to examine the relationship between mitochondrial content, mitochondrial function, and sarcopenia. Mitochondrial content and maximal mitochondrial ATP production rates (MAPR) display an inverse relationship to lifespan, while onset of MAPR decline displays a direct relationship. Muscle mitochondrial structure, sarcomere structure, and movement decline also display a direct relationship with longevity. Notably, the decline in mitochondrial network structure occurs earlier than sarcomere decline, and correlates more strongly with loss of movement, and scales with lifespan. These results suggest that mitochondrial function is critical in the ageing process and more robustly explains the onset and progression of sarcopenia than loss of sarcomere structure.