Fasting Extends Lifespan But Effective Only in Youth

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Fasting Extends Lifespan But Effective Only in Youth, Says Nature Aging Study

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Fasting Extends Lifespan But Effective Only in Youth, Says Nature Aging Study

In recent years, fasting has gained popularity in the scientific community, proving effective for weight loss and extending the lifespan of animals. Numerous studies suggest fasting has various health benefits, improving metabolic health, preventing or delaying age-related diseases, and even slowing tumor growth.

However, a recent study published on November 13, 2023, in the journal “Nature Aging” by researchers from the Max Planck Institute for Biology of Aging in Germany challenges the notion that fasting is universally beneficial for lifespan extension, particularly in aged animal models.

The research, titled “Refeeding-associated AMPKγ1 complex activity is a hallmark of health and longevity,” reveals that fasting and refeeding cycles trigger a reverse oscillation in the expression of genes encoding the AMP-activated protein kinase (AMPK) regulatory subunits Prkag1 and Prkag2 in young animals.

In contrast, aging weakens this regulation, leading to reduced Prkag1 expression in aged animals.

Transgenic fish with sustained Prkag1 expression exhibited more youthful eating and fasting responses in old age, improving metabolic health and extending lifespan.

Interestingly, the study found that in humans, Prkag1 expression decreases with age and is associated with an increased risk of multiple diseases and multidimensional frailty. This suggests that selectively activating Prkag1 may promote metabolic health and extend human lifespan.

AMPK, a key molecular regulator of energy metabolism, has previously been shown to mediate lifespan extension in invertebrate models and beneficial effects of dietary restriction.

Analyzing the impact of fasting on different age groups of zebrafish, a rapidly aging species with a lifespan of 6-7 months, researchers discovered that the fat tissue of aged fish exhibited transcriptional patterns resembling fasting. Both eating and fasting suppressed energy metabolism, reduced protein production, and hindered tissue renewal in aged fish. The visceral fat tissue of aged fish showed reduced sensitivity to food intake compared to their younger counterparts.

For young fish, fasting and refeeding cycles triggered a reverse oscillation in the expression of genes encoding AMPK regulatory subunits Prkag1 and Prkag2 in fat tissue. Prkag1 expression was inhibited by fasting and induced by refeeding. Aging weakened this regulation, resulting in decreased Prkag1 expression.

Aging alters adipose tissue’s physiological response to fasting

By genetically modifying aged fish to sustain Prkag1 expression, researchers nullified the negative effects of fasting in old age, showcasing more youthful eating and fasting responses, improved metabolic health, and extended lifespan.

Sustained activation of Prkag1 promotes metabolic health and longevity

Finally, the study examined the relevance of Prkag1 in human health and longevity. Transcriptome analysis of human subcutaneous fat tissue after fasting revealed a pattern similar to that observed in zebrafish, with upregulated Prkag2 and downregulated Prkag1 expression. Like in zebrafish, Prkag1 expression in humans declines with age and is associated with an increased risk of multiple diseases and multidimensional frailty. Higher Prkag1 levels in humans during old age were linked to reduced frailty, suggesting that selectively activating Prkag1 may promote metabolic health and extend human lifespan.

The researchers emphasize that the role of Prkag1 in promoting healthier aging in humans is not yet fully understood. Future research aims to identify molecules that can precisely activate this subunit and explore whether they can be used to positively influence aging.

In conclusion, the study suggests that selectively stimulating the Prkag1 complex could prevent age-related metabolic stagnation, promoting metabolic health and lifespan in vertebrate animals.

[Paper Link: https://doi.org/10.1038/s43587-023-00521-y]

Fasting Extends Lifespan But Effective Only in Youth, Says Nature Aging Study

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