A study of killifish by the Max Planck Institute revealed that older fish enter a state of starvation due to changes in their adipose tissue. Activating a specific subunit of AMP kinase restores health and longevity in humans, suggesting a new way to promote healthier aging in humans.
Genetic switch rescues aging fish from starvation trap.
Fasting interventions that alternate between fasting and refeeding are generally thought to improve health. However, these interventions do not work well in older animals.
The question is, why?
By studying short-lived killifish, researchers at the Max Planck Institute for the Biology of Aging in Cologne found that older fish deviate from the fasting and refeeding cycles of their youth, and even when they consume food, they permanently It was shown that the body enters a state of fasting. However, the benefits of post-fasting refeeding in old medaka fish can be restored by genetically activating specific subunits of AMP kinase, an important sensor of cellular energy.
These mutant fish experience improved health and longevity and require both fasting and refeeding to provide health benefits, which have been shown to act through AMP kinase. I am.
Medaka ages rapidly. The bright colors of their youth fade in just a few months.Credit: K. Link / Max Planck Institute for the Biology of Aging
It has already been shown in many model organisms that reducing food intake through calorie restriction or periods of fasting has positive effects on health. However, it is difficult for humans to reduce the amount they eat throughout their lifetime. To find the optimal timing for fasting, researchers introduced fasting interventions at different ages, but found that these interventions in older adults did not provide the same benefits as in younger animals.
A research team in Cologne, Germany, now investigated the effects of age-related fasting on medaka fish. Medaka is a rapidly aging fish that grows from young to old in just a few months. The researchers either starved young and old fish for several days or fed them twice a day. They found that the visceral adipose (adipose) tissue of older fish became less responsive to feeding. “Adipose tissue is known to respond most strongly to changes in food intake and plays an important role in metabolism, which is why we looked at it more closely,” said lead author of the study. explains Roberto Ripa.
It is important to alternate between fasting and meals
The researchers found that, unable to respond to the feeding phase, the adipose tissue of old fish enters a permanent state of starvation, where energy metabolism ceases, protein production decreases, and tissue does not renew. “We thought that older fish would be unable to switch to fasting after feeding. Surprisingly, the opposite was true, and older fish would be unable to switch to fasting after feeding. , they were in a state of permanent starvation,” said study leader Adam Antebi, director of the Max Planck Institute for the Biology of Aging.
Permanently fasted adipose tissue
When the researchers looked more closely at how the fat tissue of old fish differs from that of young fish, they discovered a specific protein called AMP kinase. This kinase is a cellular energy sensor and is composed of various subunits, among which the activity of the γ1 subunit decreases with age. When scientists genetically engineered this subunit to increase its activity, the starvation-like state was overcome, and the old fish became healthier and lived longer.
human aging
Interestingly, an association was also found between the γ1 subunit and human aging. Significantly lower levels of certain subunits were measured in samples from older patients. Additionally, in human samples, we were able to show that people who are less frail at older ages have higher levels of the γ1 subunit.
“Of course, we still don’t know whether the human γ1 subunit is actually involved in healthy aging. The next step is to find a molecule that precisely activates this subunit and use it to “We investigate whether this can have a positive impact on aging,” explains Adam Antebi.
Reference: “Refeeding related AMPK”γ1 Complex activity is a hallmark of health and longevity.” Roberto Ripa, Eugen Barrissa, Joachim D. Steiner, Raymond Lavoie, Andrea Annibal, Nadine Hocher, Christian Razza, Luca Dolfi, Chiara Calabrese, By Anna M. Meyer, Maria Cristina Polidori, and Roman – Ulrich Müller and Adam Antebi, November 13, 2023, natural aging.
DOI: 10.1038/s43587-023-00521-y
Source: scitechdaily.com
