Abstract
Sarcopenia, the age-related decline of muscle, is a significant and growing public health burden. C. elegans, a model organism for investigating the mechanisms of ageing, also displays sarcopenia, but the underlying mechanism(s) remain elusive. 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.
Highlights
Sarcopenia is the age-related loss of muscle mass, function and quality that impairs quality of life and is a strong predictor of disability
Loss of mitochondrial-network structure precedes the loss of sarcomere structure in ageing C. elegans muscle at 20°C
We used the model organism C. elegans to prospectively investigate sub-cellular and whole muscle changes across the lifespan
Summary
Sarcopenia is the age-related loss of muscle mass, function and quality that impairs quality of life and is a strong predictor of disability. 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, suggest that sarcopenia is an evolutionarily conserved process and whilst some evidence suggests the underlying mechanism(s) might be conserved, it remains an open question [4,5,6]. The last two decades have seen tremendous www.aging‐us.com growth in ageing research employing model organisms including the nematode C. elegans. It has a short lifespan of 2-3 weeks at 20°C, is relatively inexpensive to work with and has emerged as a powerful genomic tool for studying ageing. Research in C. elegans has led to discoveries including the regulators of the insulin signaling pathway [8], the cell death machinery [9] and genes which regulate longevity [8]
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