Buck Institute researchers have demonstrated for the first time a link between diet, circadian rhythms, eye health and lifespan in Drosophila. Publication in the June 7, 2022 issue of Nature communicationsthey also unexpectedly discovered that processes in the fly’s eye are actually driving the aging process.
Previous studies have shown in humans that there is an association between eye disorders and poor health. “Our study argues that it’s more than just a correlation – eye dysfunction can actually cause problems in other tissues,” said senior author and Buck Institute professor Pankaj Kapahi, PhD, whose lab has been showing for years that fasting and calorie restriction can improve many body functions. “We are now showing that not only does fasting improve vision, 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 came as a surprise to us,” said lead author Brian Hodge, PhD, who has done his post-study. doctorate in the laboratory of Kapahi.
The explanation for this connection, Hodge said, lies in the circadian “clocks,” the molecular machinery within every cell of every organism, which has evolved to adapt to everyday stresses, such as changes in light and temperature caused by rising and setting of the sun. These 24-hour oscillations – circadian rhythms – influence complex animal behaviors, such as predator-prey interactions and sleep / wake cycles, right up to the fine-tuning of the temporal regulation of molecular functions of gene transcription and protein translation.
In 2016 Kapahi’s lab published a study in Cell metabolism showing that fruit flies on a restricted diet had significant changes in their circadian rhythms as well as prolonged lifespan. When Hodge joined the lab in the same year, he wanted to dig deeper to understand which processes that improve circadian function were altered by the change in diet and whether circadian processes were necessary for the longer lifespan seen with. dietary restriction.
“The fruit fly has such a short lifespan, which makes it a really beautiful model that allows us to screen many things at once,” said Hodge, who is currently a scientist at Fountain Therapeutics in southern San Francisco. The study began with an extensive investigation to see which genes fluctuate circadian when flies on an unlimited diet were compared to those fed only 10% of the protein from the unlimited diet.
Immediately, Hodge noticed numerous genes that were both diet responsive and also exhibited highs and lows at different times, or “rhythms.” She then found that the rhythmic genes that activated the most with dietary restrictions all seemed to come from the eye, particularly photoreceptors, the specialized neurons in the eye’s retina that respond to light.
This discovery led to a series of experiments designed to understand how ocular function fits the story of how food restriction can extend lifespan. For example, they started experiments showing that keeping flies in constant darkness extended their life. “It seemed very strange to us,” Hodge said. “We thought flies needed light signals to be rhythmic or circadian.”
They then used bioinformatics to ask: Do genes in the eye, which are also rhythmic and responsive to dietary restrictions, affect lifespan? The answer was yes, they do.
“We always think of the eye as something we need, to provide vision. We don’t think of it as something that needs to be protected to protect the whole organism,” said Kapahi, who is also an associate professor of urology at UCSF.
Because the eyes are exposed to the outside world, he explained, the immune defenses are critically active, which can lead to inflammation that, if present for long periods of time, can cause or worsen a number of common chronic diseases. Also, light by itself can cause photoreceptor degeneration which can cause inflammation.
“Staring at computer and phone screens and being exposed to light pollution late into the night are very disturbing conditions for circadian clocks,” said Kapahi. “It messes with the eye protection and that could have consequences beyond mere vision, damaging the rest of the body and the brain.”
There is a lot to understand about the role the eye plays in an organism’s overall health and lifespan, including: how does the eye regulate lifespan and does the same effect apply to other organisms?
The biggest question raised by this work as it might apply to humans is, simply, do photoreceptors in mammals affect longevity? Probably not as much as in fruit flies, Hodge said, noting that most of the energy in a fruit fly is devoted to the eye. But because photoreceptors are just specialized neurons, he said, “the strongest link I would say 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 during l ‘aging”.
Once researchers understand how these processes work, they can begin targeting the molecular clock to decelerate aging, Hodge said, adding that it could be that humans can help maintain vision by activating clocks at all. inside of our eyes. “It could be through diet, medications, lifestyle changes … We have a lot of really interesting research ahead of us,” she said.