African killifish could hold the secret to reversing muscle aging

As we age, our muscles start to decrease. Called sarcopenia, it happens to all of us, but no one ever understands why or how it happens. Now new research from the Australian Regenerative Medicine Institute (ARMI) at Monash University has used a surprising animal model – the African killifish – to reveal that towards the end of life, our muscles actually revert to their “early life” state, slowing death. . These findings could provide clues for slowing, stopping, or even reversing age-related loss of muscle mass and strength.

Research published in Aging Cell and led by Professors Peter Currie and Dr Avnika Ruparelia, from ARMI and the University of Melbourne, is important because of the predicted dramatic increase in the prevalence and severity of sarcopenia across the global population.

According to Professor Currie, “…there is an urgent need to understand the mechanisms driving sarcopenia, so that we can identify and implement appropriate medical interventions to promote healthy muscle aging,” he said.

African turquoise killifish, Nothobranchius furzeri has recently emerged as a new model for the study of aging. Killifish have the shortest known life span of any vertebrate species that can be bred in captivity. The killifish’s life begins with the African rains, creating seasonal rain ponds where the fish hatch, grow rapidly and mature in just two weeks, and then reproduce daily until the pond dries up.

Importantly, their short life span is accompanied by the symptoms of aging that we see in humans – including the appearance of cancerous lesions in the liver and gonads, reduced regenerative capacity of the limbs, in this case the fins, and genetic characteristics characteristic of human aging such as reduced mitochondrial DNA copy number and function and telomere shortening.

According to Dr Ruparelia, this research is the first to use killifish to study sarcopenia.

“In this study, we performed a thorough cellular and molecular characterization of skeletal muscle from early life, late life, and late stages of very old life, revealing many similarities to sarcopenia in humans and other mammals,” he said.

Surprisingly, the researchers also found the same metabolic features of aging were reversed during the later stages of life, “suggesting that in very old animals, there may be
mechanisms are in place that prevent further deterioration of the health of the skeletal muscles, which may ultimately contribute to the extension of their life span,” said Dr Ruparelia.

“Importantly, the late-life stage in which we observed an increase in muscle health perfectly coincided with the stage when mortality decreased. We therefore postulated that improved muscle health may be an important factor contributing to extended life span in very old individuals.”

To better understand the mechanisms behind this, the research team surveyed fish metabolism at different stages of the aging process. This experiment surprisingly revealed that certain features of the metabolism of the oldest fish were actually rejuvenated to resemble that of the younger fish. This highlights the important role of lipid metabolism in this rejuvenating process. By using drugs that regulate the formation of certain lipids, rejuvenation of aging muscles can be achieved.

“During very old age, there is a marked depletion of lipids, which are the main energy reserve in our cells,” explained senior author Prof Currie.

“We believe that this mimics the state of caloric restriction, a process known to prolong the life span of other organisms, resulting in the activation of downstream mechanisms that ultimately allow animals to maintain nutritional balance and live longer. A similar process is seen in the muscles of highly trained athletes.”

Dr Ruparelia continued by saying, “The idea that muscle aging is reversible, and potentially treatable with drugs that can manipulate cell metabolism, is an exciting prospect especially given the social, economic and healthcare costs associated with an ever-increasing aging population. around the world. We are excited about the potential of the killifish model, and are very grateful to the Winston Churchill Trust for funding, and to the Hon Dr Kay Patterson for his assistance in establishing import regulations to set up Australia’s first and only killifish facility. We now have a unique opportunity to study the biological processes that regulate aging and age-related diseases, and to investigate strategies to promote healthy aging.”

This publication is an accumulation of collaboration between researchers from:

• Australian Institute of Regenerative Medicine (Australia)
• Monash Biomedical Discovery Institute (Australia)
• University of Melbourne (Australia)
• Muscle Research Center (Australia)
• Peter MacCallum Cancer Center (Australia)
• Leibniz Institute on Aging – Fritz Lipmann Institute (Germany)

Further information

Currie’s group was curious about the biological mechanisms of zebrafish, a freshwater fish native to Southeast Asia. Zebrafish are used in scientific research to understand human genetics and the biological processes of human disease. For more information about Professor Peter Currie and his group at ARMI, please visit the Currie Groups page. You can contact Dr Avnika Ruparelia or Professor Peter Currie via (email protected) and (email protected) respectively.