Fruit fly intestine may hold secret to the fountain of youth

The positive effect of calorie restriction on lifespan in many organisms is well established, but scientists are still working to understand the mechanism. The latest finding, in fruit flies, is that artificially increasing the number of mitochondria in the cells of the intestines – which happens naturally under conditions of calorie restriction – may be partially responsible for the effect.

Fruit fly intestine may hold secret to the fountain of youth

This chain of connections between the mitochondria and longevity inspired Jones and her colleague to investigate what happens when the PGC-1 gene is forced into overdrive. To do this, they used genetic engineering techniques to boost the activity of the fruit fly equivalent of the PGC-1 gene. The flies (known as Drosophila melanogaster) have a short lifespan, allowing the scientists to study aging and longevity in ways that aren’t as feasible in longer-lived organisms such as mice or human.

The researchers found that boosting the activity of dPGC-1, the fruit fly version of the gene, resulted in greater numbers of mitochondria and more energy-production in flies – the same phenomenon seen in organisms on calorie restricted diets. When the activity of the gene was accelerated in stem and progenitor cells of the intestine, which serve to replenish intestinal tissues, these cellular changes correspond with better health and longer lifespan. The flies lived between 20 and 50 percent longer, depending on the method and extent to which the activity of the gene was altered.

The research suggests that the mechanism by which health and longevity are increased involves greater robustness in the intestinal tissue as a result of having more mitochondria.

Modulation of Longevity and Tissue Homeostasis by the Drosophila PGC-1 Homolog

[W]e show that overexpression of the Drosophila PGC-1 homolog (dPGC-1/spargel) is sufficient to increase mitochondrial activity. Moreover, tissue-specific overexpression of dPGC-1 in stem and progenitor cells within the digestive tract extends life span. Long-lived flies overexpressing dPGC-1 display a delay in the onset of aging-related changes in the intestine, leading to improved tissue homeostasis in old flies. Together, these results demonstrate that dPGC-1 can slow aging both at the level of cellular changes in an individual tissue and also at the organismal level by extending life span. Our findings point to the possibility that alterations in PGC-1 activity in high-turnover tissues, such as the intestine, may be an important determinant of longevity in mammals.

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