A research study on killifish by the Max Planck Institute exposed that older fish are stuck in a fasting state due to changes in fat. Activating a specific subunit of AMP kinase restored their health and durability, meaning new approaches for promoting healthier aging in humans.Genetic switch saves aging fish from constant fasting trap.Fasting interventions, which involve rotating durations of fasting and refeeding, are typically believed to improve health. These interventions dont work as well in old animals.The concern is: Why?By studying the temporary killifish, researchers at the Max Planck Institute for Biology of Ageing in Cologne have revealed that older fish deviate from a vibrant fasting and refeeding cycle, and rather get in a state of continuous fasting, even when consuming food. The advantages of refeeding after fasting in old killifish can be brought back by genetically triggering a particular subunit of AMP kinase, an essential sensor of cellular energy.These mutant fish experienced enhanced health and longevity, indicating that both fasting and refeeding are needed to give health advantages and act through AMP kinase to do so.Killifish age in fast motion. The intense colors of their youth fade after just a couple of months. Credit: K. Link/ Max Planck Institute for Biology of AgeingIt has currently been displayed in lots of design organisms that a lowered diet plan, either through calorie restriction or periods of fasting, has a positive impact on health. Nevertheless, it is challenging for human beings to consume less throughout life. In order to discover the most suitable timing for fasting, researchers introduced fasting interventions at different ages, discovering that these interventions in older age do not yield the same benefits as they carry out in younger animals.A group of scientists from Cologne, Germany, has now examined the age-related fasting effects in killifish. Killifish are rapid-aging fish that go from young to old in just a couple of months. The researchers either fasted young and old fish for a couple of days or fed them twice a day. They found that the visceral adipose (fat) tissue of old fish became less responsive to feeding. “The adipose tissue is known to react most highly to variations in food intake and has an important role in metabolism. Thats why we looked at it more closely,” describes Roberto Ripa, lead author of the study.Alternation Between Fasting and Eating Is CrucialThe scientists discovered that the failure to react to the feeding stage set the fat tissue of old fish in a long-term state of fasting: basal metabolism is shut down, protein production is minimized, and tissue is not restored. “We had assumed that old fish would not have the ability to change to fasting after feeding. Remarkably, the opposite held true, the old fish remained in an irreversible fasting state, even while eating food” states Adam Antebi, Director at the Max Planck Institute for Biology of Ageing and leader of the study.Adipose Tissue in a Permanent Fasting StateWhen the researchers looked more closely at how the fat of the old fish varied from that of the young, they came throughout a particular protein called AMP kinase. This kinase is a cellular energy sensing unit, and is made up of different subunits, of which the activity of the γ1 subunit decreases with age. When the scientists increased the activity of this subunit through hereditary modification, the fasting-like state was combated and the old fish were much healthier and even lived longer.Human AgingInterestingly, a link was also discovered between the γ1-subunit and human aging. Significantly lower levels of the specific subunit were determined in samples from elderly patients. In addition, it was possible to show in the human samples: the less frail an individual is in aging, the higher the level of the γ1-subunit.” Of course, we dont yet understand whether in people the γ1-subunit is really accountable for much healthier aging. In the next step, we will search for molecules that activate exactly this subunit and examine whether we can utilize them to favorably affect aging,” explains Adam Antebi.Reference: “Refeeding-associated AMPKγ1 complex activity is a trademark of health and durability” by Roberto Ripa, Eugen Ballhysa, Joachim D. Steiner, Raymond Laboy, Andrea Annibal, Nadine Hochhard, Christian Latza, Luca Dolfi, Chiara Calabrese, Anna M. Meyer, Maria Cristina Polidori, Roman-Ulrich Müller and Adam Antebi, 13 November 2023, Nature Aging.DOI: 10.1038/ s43587-023-00521-y.
These interventions do not work as well in old animals.The question is: Why?By studying the brief killifish, researchers at the Max Planck Institute for Biology of Ageing in Cologne have shown that older fish deviate from a younger fasting and refeeding cycle, and rather go into a state of continuous fasting, even when ingesting food. In order to find the most suitable timing for fasting, researchers introduced fasting interventions at various ages, discovering that these interventions in older age do not yield the same benefits as they do in more youthful animals.A team of researchers from Cologne, Germany, has now investigated the age-related fasting results in killifish. Thats why we looked at it more closely,” explains Roberto Ripa, lead author of the study.Alternation Between Fasting and Eating Is CrucialThe scientists discovered that the failure to react to the feeding stage set the fat tissue of old fish in a permanent state of fasting: energy metabolic process is shut down, protein production is lowered, and tissue is not renewed. Surprisingly, the opposite was real, the old fish were in an irreversible fasting state, even while eating food” says Adam Antebi, Director at the Max Planck Institute for Biology of Ageing and leader of the study.Adipose Tissue in a Permanent Fasting StateWhen the researchers looked more closely at how the fatty tissue of the old fish differed from that of the young, they came throughout a particular protein called AMP kinase.