Summary: A new study of Drosophila shows a link between circadian rhythm, diet, lifespan and eye health. Unexpectedly, researchers found processes in the fly’s eye that seem to accelerate the aging process.
Source: Buck Institute
Buck Institute researchers have demonstrated for the first time a link between diet, circadian rhythm, eye health and lifespan in Drosophila.
Published in the June 7, 2022 issue of nature communicationThey also 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 argues that it’s more than a correlation: Dysfunction of the eye can actually lead to problems in other tissues,” said senior author and Buck Institute Professor Pankaj Kapahi, Ph.D., whose lab has studied this fasting for years. and calorie restriction demonstrated can improve many functions of the body.
“We are now showing that fasting not only improves vision, but that the eye actually plays a role in influencing lifespan.”
“The finding 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, Ph.D., who was doing his postdoctoral studies in Kapahi’s lab.
The explanation for this connection, Hodge said, lies in circadian “clocks,” the molecular machinery in every cell of every organism that evolved to adapt to daily stresses, such as changes in light and temperature, caused by the rising and setting of the sun sun are caused sun.
These 24-hour oscillations—circadian rhythms—influence complex animal behaviors, such as B. predator-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 showed that in addition to increasing lifespan, fruit flies with restricted diets also exhibited significant changes in their circadian rhythm.
When Hodge came to the lab later that year, he wanted to dig deeper to find out what processes that improve circadian function were altered by the dietary change and whether circadian processes were required for the longer lifespan seen with dietary restriction.
“The fruit fly has such a short lifespan, which makes it a really nice model that we can use to study many things at once,” said Hodge, who is currently a scientist at Fountain Therapeutics in South San Francisco.
The study began with a broad survey to see which genes vibrate circadian when flies fed unrestricted diets were compared to those fed only 10 percent of the unrestricted diet protein.
Hodge immediately noticed numerous genes that both responded to diet and showed peaks and valleys at different times, or “rhythmically.”
He then discovered that the rhythmic genes most activated during dietary restrictions all seemed to come from the eye, specifically from photoreceptors, the specialized neurons in the eye’s retina that respond to light.
This finding led to a series of experiments aimed at understanding how eye function fits into the story of how dietary restriction can extend lifespan. For example, they conducted experiments showing that keeping flies in constant darkness increased their lifespans.
“That struck us as very strange,” Hodge said. “We thought flies must have rhythmic or circadian light signals.”
They then used bioinformatics to ask: do the genes in the eye, which are also rhythmic and respond to dietary restrictions, affect lifespan? The answer was yes, they do.
“We always think of the eye as something that serves us to enable seeing. We don’t see 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 explains, the immune system is critically active there, which can lead to inflammation that, if left there for long periods of time, can cause or exacerbate a variety of common chronic diseases.
Additionally, light 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 conditions that are very disruptive to circadian clocks,” Kapahi said.
“It messes with the eye’s protection and that could have consequences that go beyond vision and damage 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 organisms?
The biggest question this work raises, 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 since photoreceptors are just specialized neurons, he said, “I would argue that the stronger connection is the role that circadian function plays in neurons in general, particularly with dietary restrictions, and how that can be harnessed to improve neuronal function.” to be maintained during aging.”
Once researchers understand how these processes work, they can start targeting the molecular clock to slow aging, Hodge said, adding that humans could potentially help maintain vision by changing the clocks in our eyes activate. “It could be through diet, medication, lifestyle changes… Lots of really interesting research ahead,” he said.
About this news from neuroscientific research
Author: press office
Source: Buck Institute
Contact: Press Office – Buck Institute
Picture: The image is in the public domain
Original research: Open access.
“Diet restriction and the transcription factor clock delay ocular aging to prolong lifespan in Drosophila” by Brian Hodge et al. nature communication
Food restriction and the transcription factor clock delay ocular aging to prolong the lifespan of Drosophila
Many vital processes in the eye are subject to circadian regulation, and circadian dysfunction has emerged as a potential driver of ocular aging. Dietary restriction is one of the most robust life-prolonging therapies and reinforces the circadian rhythm with age.
Here we show that dietary restriction increases lifespan Drosophila melanogaster by promoting circadian homeostatic processes that protect the visual system from age- and light-related damage.
Alteration of the positive transcription factor for the limb nuclear molecular clock, CLOCK, or CLOCK parent genes, accelerates visual senescence, induces a systemic immune response, and shortens lifespan.
Flies that are dietally restricted are protected from the lifespan-shortening effects of photoreceptor activation. Conversely, inactivation of photoreceptors, achieved by mutating rhodopsin or housing flies in constant darkness, primarily increases the lifespan of flies reared on a nutrient-rich diet.
Our results establish the eye as a nutritionally sensitive lifespan modulator and suggest that vision is an antagonistic pleiotropic process that contributes to aging of the organism.