In an animal model of aging, the Australian Regenerative Medicine Institute (AMRI) at Monash University found that muscles “rejuvenate” to approximate their early metabolic condition near the end of life. Aging Cell publishes the study.
Studying aging in animals
Biomedical researchers use animals to study human biology. Laboratory models are chosen for their biological similarities to people, sensitivity to human illnesses, and shorter lifespans.
The African turquoise killifish, Nothobranchius furzeri, is the shortest-lived vertebrate species that can be grown in a lab. Like humans, killifish have liver and gonad cancer, shortened telomeres, and decreased limb regeneration. These traits have made it a popular laboratory model for human aging, a major social issue.
In the new study, renowned developmental evolutionary and stem cell biologist Professor Peter Currie at AMRI and Dr. Avnika Ruparelia, senior lecturer in anatomy and physiology at the University of Melbourne, led scientists in using killifish to study sarcopenia, a gradual loss of muscle mass and strength that occurs in aging.
How sarcopenia causes muscle loss is unknown. “There is a pressing need to understand the mechanisms that drive sarcopenia, so we can identify and implement suitable medical interventions to promote healthy muscle aging,” Currie said. The Australian-German research team claims this is the first time the model has been used to analyze the illness.
Older animals avoid skeletal muscle degeneration.
Currie and colleagues studied African killifish skeletal muscle from early to late life at the molecular and cellular levels. “We reveal that many of the characteristics examined, including muscle stem cell number and muscle innervation deteriorate with increasing age, consistent with the presentation of sarcopenia,” the scientists write in the report.
“We reveal a second subset of characteristics, composed of muscle fiber size and proteolysis, that deteriorated in aged fish but were found to improve in the extremely old late-life fish,” they say.
Ruparelia implies that extremely elderly animals may have a system that prevents skeletal muscle degradation, extending their lives.
“Importantly, the late-life stage when we observed improved muscle health perfectly coincides with a stage when mortality rates decline. We thus infer that improving muscular health may be a crucial component contributing to the extension of longevity in really elderly individuals,” she said.
Late-life muscles “rejuvenate”—how?
The team tried to understand this surprise discovery. Systems metabolomics revealed all metabolomic processes in a cell or tissue sample at a particular timepoint.
Currie and colleagues observed that the metabolism of the oldest killifish “rejuvenates” to resemble that of younger fish. Mitohormesis, a stress resistance mechanism, activated. The researchers hypothesized that this enhanced lipid metabolism and nutritional balance in the really elderly sample, extending their lifespan.
“Lipids, our cells’ main energy reserves, deplete dramatically in extreme old age,” Currie added. This mimics calorie restriction, which extends longevity in other species, and activates downstream systems to help the animal maintain nutritional balance and live longer. High-performance athletes’ muscles undergo a similar process.”
Is muscle aging reversible?
A medication that regulates lipid synthesis might cause rejuvenation, according to the researchers. Resveratrol increased killifish body weight significantly.
“The idea that muscle aging may be reversible, and potentially treatable by drugs that can manipulate a cell’s metabolism, is exciting,” Ruparelia said. “We have a unique opportunity to study biological processes regulating aging and age-related diseases and to investigate strategies to promote healthy aging.”