Researchers at the Max Planck Institute for Biology of Ageing in Cologne have gained crucial insights into the relationship between fasting, feeding, and healthy aging.
“Late-life-initiated dietary interventions show limited efficacy in extending longevity or mitigating frailty, yet the underlying causes remain unclear,” wrote the researchers.
“Here we studied the age-related fasting response of the short-lived killifish Nothobranchius furzeri.”
The experts discovered that the cycle of fasting and refeeding, previously thought to benefit health, is less effective in older organisms due to a deviation from the youthful fasting-refeeding cycle.
The study highlighted a unique phenomenon in older killifish. Despite consuming food, they remained in a state of perpetual fasting. This was attributed to changes in the visceral adipose tissue, which became less responsive to feeding in older fish.
“The adipose tissue is known to react most strongly to variations in food intake and has an important role in metabolism. That’s why we looked at it more closely,” explained study lead author Roberto Ripa.
Further investigation led to a significant discovery involving AMP kinase, a key cellular energy sensor. The research identified the γ1 subunit of this kinase, whose activity diminishes with age.
Remarkably, the team found that the benefits of refeeding after fasting in old killifish can be restored by genetically activating this specific subunit. Through this genetic modification, the fasting-like state was counteracted and the old fish were healthier and even lived longer.
“We had assumed that old fish would not be able to switch to fasting after feeding. Surprisingly, the opposite was true, the old fish were in a permanent fasting state, even while eating food,” said Adam Antebi, director at the Max Planck Institute for Biology of Ageing.
This study not only sheds light on the fasting-refeeding cycle’s role in aging but also establishes a connection between the γ1-subunit and human aging.
Lower levels of this subunit were observed in older patients, with a correlation between higher γ1-subunit levels and less frailty in old age.
“Of course, we don’t yet know whether in humans the γ1-subunit is actually responsible for healthier aging. In the next step, we will try to find molecules that activate precisely this subunit and investigate whether we can use them to positively influence ageing,” explained Antebi.
This research underscores the importance of alternating between fasting and eating, especially as it pertains to aging, and opens new avenues for exploring interventions that could promote healthier aging in humans.
The study is published in the journal Nature Aging.
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