Jun 7, 2022
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Link found between diet, eye health and life expectancy

Link found between diet, eye health and life expectancy

Researchers at the Buck Institute have demonstrated for the first time the relationship between diet, circadian rhythms, eye health and longevity in Drosophila. Publishing the results in the June 7, 2022 issue of Nature Communications, they additionally and unexpectedly found that processes in the fly’s eye actually drive the aging process.

Previous studies have shown in humans that there is a link between eye diseases and poor health. “Our study proves that this is more than a correlation: eye dysfunction can lead to problems in other tissues,” said study senior author and Baka Institute professor Pankaj Kapahi, Ph.D., whose lab has been demonstrating for years that fasting and calorie restriction can improve many bodily functions. “Now we show that fasting not only improves vision, but also affects life expectancy.”

“The fact that the eye itself, at least in the fruit fly, can directly regulate lifespan came as a surprise to us,” said study lead author Brian Hodge, Ph.D., who was a postdoctoral fellow at Kapakha’s lab.

The explanation for this connection, according to Hodge, lies in the circadian “clock” – the molecular machinery inside every cell of any organism that has evolved to adapt to daily stresses, such as changes in light and temperature caused by sunrise and sunset. These 24-hour fluctuations – circadian rhythms – influence complex animal behaviors such as predator-prey interactions and sleep/wake cycles, to the point of fine-tuning the timing of the molecular functions of gene transcription and protein translation.

In 2016, Kapakha’s lab published a study in the journal Cell Metabolism that showed that fruit flies on a restricted diet, in addition to increasing lifespan, experienced significant changes in circadian rhythms. When Hodge joined the lab that same year, he wanted to gain a deeper understanding of which processes that improve circadian function were altered by dietary changes, and whether circadian processes were necessary for the increased lifespan seen with dietary restriction.

“The fruit fly has such a short lifespan, which makes it a really great model to explore a lot of things at once,” says Hodge, who is currently a scientist at Fountain Therapeutics in South San Francisco. The study began with a broad survey to find out which genes fluctuate in a circadian rhythm when flies on an unlimited diet are compared to flies that get just 10 percent of the protein from an unlimited diet.

Immediately, Hodge noticed many genes that not only responded to the diet, but also showed ups and downs at different points in time, or “rhythm”. He then found that the rhythmic genes that were most activated by dietary restriction all seemed to come from the eye, specifically from photoreceptors, specialized neurons in the retina that respond to light.

This finding led to a series of experiments aimed at understanding how the function of the eye fits into the story of how dietary restriction can prolong life. For example, they set up experiments showing that keeping flies in constant darkness increases their lifespan. “It seemed very strange to us,” says Hodge. “We thought the flies needed lighting to be rhythmic, or circadian.”

They then used bioinformatics to ask the question: Do genes in the eye, which are also rhythmic and responsive to food restriction, affect longevity? The answer was positive.

“We always think of the eye as something that serves us by providing vision. We don’t think of it as something that needs to be protected to protect the whole body,” said Kapahi, who is also an associate professor Urology at UCSF.

Because the eyes are exposed to the outside world, he explained, their immune defenses are critically active, which can lead to inflammation, which, if present for a long time, can cause or worsen various common chronic diseases. In addition, light itself can cause photoreceptor degeneration, which can lead to inflammation.

“Looking at computer and phone screens and being exposed to light pollution at night are conditions that really disrupt the circadian clock,” Kapahi says. “This compromises the protection of the eyes, which can have consequences not only for vision, but also for the rest of the body and the brain.”

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