Buck Institute researchers have shown for the first time a link between diet, circadian rhythms, eye health and life expectancy in drosophila. Publication in the June 7, 2022 edition of Nature CommunicationFurthermore, they unexpectedly discovered that processes in the fly’s eye actually drive the aging process.
Previous studies have shown in humans that there is an association between eye disorders and poor health. “Our study argues that this is more than a correlation: Dysfunction in the eye can actually lead to problems in other tissues,” said lead author and Buck Institute professor Pankaj Kapahi, PhD, whose lab has shown for years that fasting and calorie restriction can improve many bodily functions. “Now we show that fasting not only improves eyesight, but that the eye actually plays a role in influencing lifespan. »
“The discovery that the eye itself, at least in the fruit fly, can directly regulate lifespan was a surprise to us,” said lead author Brian Hodge, PhD, who did his postdoctoral studies in Kapahi’s lab. .
The explanation for this connection, Hodge said, lies in circadian “clocks,” the molecular machinery within every cell of every organism that has evolved to adapt to everyday stresses, such as changes in light and temperature caused by sunrise and the sunset. Sun. These 24-hour oscillations (circadian rhythms) affect complex animal behaviors, such as predator-prey interactions and sleep/wake cycles, to fine-tune the temporal regulation of molecular functions of gene transcription and protein translation.
In 2016, Kapahi’s lab published a study in Cellular metabolism showing that fruit flies on a restricted diet exhibited significant changes in their circadian rhythms in addition to extending their lifespan. When Hodge joined the lab later that year, he wanted to dig deeper to determine which processes that enhance circadian functions were altered by the change in diet, and whether circadian processes were necessary for the longer lifespan observed with restriction. food.
“The fruit fly has such a short lifespan, which makes it a really good model that allows us to detect a lot of things at once,” said Hodge, who is currently a scientist at Fountain Therapeutics in south San Francisco. The study began with a large survey to see which genes oscillated circadianally when flies on an unrestricted diet were compared to those fed just 10% of the protein in the unrestricted diet.
Right away, Hodge noticed many genes that reacted to the diet and also showed ups and downs at different times, or “rhythms.” He then discovered that the rhythmic genes most activated by food restriction seemed to come from the eye, specifically from photoreceptors, specialized neurons in the eye’s retina that respond to light.
This discovery led to a series of experiments designed to understand how eye function fits into the story of how dietary restriction can prolong life. For example, they set up experiments showing that keeping flies in constant darkness prolonged their lifespan. “It felt very strange to us,” Hodge said. “We thought that flies needed light signals to be rhythmic or circadian. »
They then used bioinformatics to ask: do eye genes that are also rhythmic and sensitive to dietary restrictions influence lifespan? The answer was yes.
“We always think of the eye as something that serves us, to give us vision. We don’t see it as something that needs to be protected to protect the whole body,” said Kapahi, who is also an assistant professor of urology at UCSF.
As the eyes are exposed to the outside, he explained, the immune defenses are highly active there, which can lead to inflammation that, when present for long periods of time, can cause or aggravate various current chronic diseases. Also, light alone can cause photoreceptor degeneration, which can cause inflammation.
“Looking at computer and phone screens and being exposed to light pollution late at night are conditions that are very detrimental to circadian clocks,” Kapahi said. “It spoils the protection of the eyes and could have consequences beyond vision, damaging the rest of the body and the brain. »
There is much to understand about the role the eye plays in the overall health and lifespan of an organism, including: how does the eye regulate lifespan, and does the same effect apply to other organizations?
The most important question raised by this work as it could be applied to humans is, in a nutshell, do photoreceptors in mammals affect longevity? Probably not as much as in fruit flies, Hodge said, noting that most of a fruit fly’s energy is spent in the eye. But since photoreceptors are just specialized neurons, he said, “I’d say the strongest link is the role that circadian function plays in neurons in general, especially with dietary restrictions, and how these can be harnessed to maintain neuronal function over time.” throughout aging.
Once researchers understand how these processes work, they can begin to target the molecular clock to slow aging, Hodge said, adding that humans can help maintain vision by turning on clocks in our eyes. “It could be through diet, medication, lifestyle changes… We’re looking forward to a lot of really interesting research,” she said.
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