Vitamin D Influences Longevity Genes And Improves Protein Stability

Posted on 26 October 2016

Vitamin D has wide beneficial effects in C. elegans – engaging known longevity genes, increasing median lifespan by 33%, and even slowing protein misfolding  

With the vast majority of cells carrying vitamin D receptors, we know the ‘sunshine’ vitamin is an influential molecule in the body, with functions beyond simply calcium absorption and bone growth. Vitamin D deficiency has in fact been linked to a range of cancers, heart disease and depression, but we still don’t really know why and how this deficiency increases disease risk. 

A fresh look

Research at the Buck Institute has revealed some fascinating information about vitamin D’s role in the model organism C. elegans, the nematode worm. The vitamin appeared to activate and associate with known longevity genes, as well as influencing a host of processes associated with human diseases. 

Cholecalciferol (Vitamin D3), the circulating form of the vitamin produced after sunlight exposure, before conversion to the active version Calcitriol in later steps 

Cholecalciferol (Vitamin D3), the circulating form of the vitamin produced after sunlight exposure, before conversion to the active version Calcitriol in later steps 

“Vitamin D engaged with known longevity genes – it extended median lifespan by 33 percent and slowed the aging-related misfolding of hundreds of proteins in the worm. Our findings provide a real connection between aging and disease and give clinicians and other researchers an opportunity to look at vitamin D in a much larger context”

Improving protein homeostasis

An especially striking finding of the study was that vitamin D impacts on protein homeostasis and folding – meaning that it helps keep the protein production and maintenance line working correctly. We know that a collapse of this maintenance is a critical issue in age, with many misfolded proteins causing aggregates that wreak havoc across a range of tissues in diseases like Alzheimer’s. In C. elegans, the vitamin targets the pathways IRE-1, XBP-1, and SKN-1; these are all linked with stress response and cellular maintenance. 

“Vitamin D3, which is converted into the active form of vitamin D, suppressed protein insolubility in the worm and prevented the toxicity caused by human beta-amyloid which is associated with Alzheimer’s disease. Given that aging processes are thought to be similar between the worm and mammals, including humans, it makes sense that the action of vitamin D would be conserved across species as well. Vitamin D3 reduced the age-dependent formation of insoluble proteins across a wide range of predicted functions and cellular compartments, supporting our hypothesis that decreasing protein insolubility can prolong lifespan”

What about humans?

Mapping of several bone diseases onto levels of vitamin D (calcidiol) in the blood

Mapping of several bone diseases onto levels of vitamin D (calcidiol) in the blood

Many of these critical processes are well conserved down the evolutionary tree, and it’s likely vitamin D affects similar genes in humans. While it may have a less pronounced benefit in humans, the study adds weight behind recent evidence and suggests that vitamin D is potentially undervalued. Developed nations often have particularly sedentary lifestyles with little outside exposure, and those individuals with darker skin tones are especially vulnerable to deficiency. Currently the IOM recommends supplementing 600 International Units (IU) per day up to 70 years old, and 800 IU daily for those above. However, other organisations have now stated the required figure is likely somewhere between 800 to 2,000 IU. Supplementation above 4000 IU is linked to raised blood calcium which is damaging to vascular tissue, but aside from that D3 is known to be safe, cheap and well tolerated. 

“We’ve been looking for a disease to associate with vitamin D other than rickets for many years and we haven’t come up with any strong evidence. But if it’s a more global marker of health or longevity as this paper suggests, that’s a paradigm shift. Now we’re talking about something very different and exciting. This work is really appealing and challenging to the field. Vitamin D influences hundreds of genes – most cells have vitamin D receptors, so it must be very important”


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