Sometimes there are strange and unexpected healthy connections in the human body. For example, the intestinal microbiome – the trillions of bacteria and other microbes that live in our digestive tract – may have links to weight loss, Lou Gehrig’s illness, autism, COVID-19 importanceand drug safety and efficacy.
Now researchers have found another surprising relationship. In a fly experiment, they discovered that the aging process is driven by processes in the eye.
Scientists have for the first time demonstrated a link between diet, diurnal rhythms, eye health and life expectancy in Drosophila. Published in the June 7, 2022 issue of the magazine Nature communicationsresearchers at the Buck Institute have additionally and unexpectedly found that processes in the fly’s eye actually lead to 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 a correlation: malfunction of the eye can actually cause problems in other tissues,” said senior author and professor at the Buck Institute Pankaj Kapahi, PhD, whose lab has proven over the years that fasting and calorie restriction can improve many. functions of the body. “We are now showing that not only does fasting improve eyesight, but the eye actually plays a role in influencing life expectancy.”
“The finding that the eye itself, at least on the fruit fly, can directly regulate life expectancy was a surprise to us,” said lead author Brian Hodge, PhD, who did his postdoctoral studies in Kapahi’s lab.
The explanation for this link, Hodge said, lies in circumscribed “clocks,” the molecular machinery within each cell of each organism that evolved to adapt to everyday stresses, such as changes in light and temperature caused by the rise and fall of the earth. body. sun. These 24-hour oscillations – circadian rhythms – affect complex animal behaviors, such as prey-prey interactions and sleep / wake cycles, to fine-tuning 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 had significant changes in their diurnal rhythms in addition to prolonging lifespan. When Hodge joined the lab later that year, he wanted to dig deeper to find out which processes that enhance diurnal functions were altered by the diet change, and whether diurnal processes were required for the longer lifespan seen with dietary restriction.
“The fruit fly has such a short lifespan, making it a really beautiful model that allows us to examine many things at once,” said Hodge, who is currently a scientist at Fountain Therapeutics in South San Francisco. The study began with an extensive survey to see what genes oscillate in circadian fashion when flies with an unrestricted diet were compared to those eaten only 10 percent of the protein from the unrestricted diet.
Immediately, Hodge noticed many genes that were both diet-responsive and also exhibiting ups and downs at different time points, or “rhythmic” ones. He then discovered that the rhythmic genes that were activated most with dietary restriction all appeared to come from the eye, specifically from photoreceptors, the specialized neurons in the retina of the eye that respond to light.
This finding 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 extended their lifespan. “That seemed very strange to us,” said Hodge. “We thought flies needed the cues to be rhythmic or diurnal.”
They then used bioinformatics to ask: Do the genes in the eye, which are also rhythmic and responsive to dietary restriction, affect life expectancy? The answer was yes, they do.
“We always think of the eye as something that serves us 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 assistant professor of urology at UCSF.
Because the eyes are exposed to the outside world, he explained, the immune defenses there are critically active, which can lead to inflammation, which, when present for long periods of time, can cause or worsen various common chronic diseases. Moreover, light in itself can cause photoreceptor degeneration which can cause inflammation.
“Watching computer and phone screens, and being exposed to light pollution until well into the night are very worrying conditions for daytime watches,” Kapahi said. “It messes up eye protection and that could have consequences beyond just 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 life of an organism, including: how does the eye regulate life expectancy, and does the same effect apply to other organisms?
The biggest question posed by this work as to how 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 the majority of energy in a fruit fly is devoted to the eye. But because photoreceptors are only specialized neurons, he said, “the stronger link I would argue is the role that circadian function plays in neurons in general, especially with dietary restrictions, and how these can be used to maintain neuronal function. as you get older. “
Once researchers understand how these processes work, they can begin targeting the molecular clock to slow aging, Hodge said, adding that it may be that humans could help maintain vision by activating the clocks within our eyes. “It could be through diet, drugs, lifestyle changes … A lot of really interesting research is going on,” he said.
Reference: “Dietary restriction and the transcription factor clock delay eye aging to prolong life expectancy in Drosophila” 7 June 2022, Nature communications.
DOI: 10.1038 / s41467-022-30975-4
Other Buck researchers involved in the study include Geoffrey T. Meyerhof, Subhash D. Katewa, Ting Lian, Charles Lau, Sudipta Bar, Simon Melov, and Birgit Schilling. Additional contributors include: Nicole Leung, Department of Neurobiology, Stanford University; David Li-Kroeger; Department of Neurology, Baylor College of Medicine; and Menglin Li and Craig Montell, Neuroscience Research Institute and Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara.
Acknowledgments: This work was supported by grants awarded to the DC by the American Federation for Aging Research, NIH grants R01 R01AG038688 and AG045835 and the Larry L. Hillblom Foundation. BAH is supported by NIH / NIA T32 award AG000266 and CM is supported by NIH / NEI award EY008117 and EY010852. We acknowledge the Buck Institute Proteomics Core and the instrumentation support of the NCRR joint instrument grant 1S10 OD016281.