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Latest skin ageing research from the Birch-Machin lab

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Pollution, niacinamide and solar light, oh my!

This year has been been a busy year for skin ageing research. Since January this year, 3 major publications have come out from the Birch-Machin group. We all know ultraviolet light is bad for your skin, but what about infrared and visible light? How do these interact with each other and impact the skin? Catherine Bonn, Eyman Rashdan and Laura Hudson all worked towards finding an answer in this Faseb paper. Pollution is quite a hot topic for skin damage at the moment, and Wil Reynold’s Faseb paper delves into the impact of urban dust in skin cells. You may have seen niacinamide added to skincare products, but what does it do? Work from Dr Amy Bowman contributed to this Ageing Cell paper, trying to turn back the mitochondrial biological clock. Keep reading to discover the main findings.

Solar light joins forces to create a perfect storm of skin damage

We protect against UV, what about the rest of the light?

In the 1990’s, there was arguments about whether or not UVA was really that big of a deal. It doesn’t cause direct DNA damage and has less energy than UVB, why should we worry? We now know it still caused DNA damage, but indirectly through the production of reactive oxygen species (ROS). ROS gets produced in response to stress and damage to signal the cell to fix it. But when the cell is under constant stress this ROS starts reacting with other parts of the cell, and is one of the leading causes of sun induced ageing signs. So we know we need to protect against high energy ultraviolet light, and there is no shortage of products to help you!

But what about the other light from the sun? That is visible (Vis) light and infrared (IR). Catherine, Eyman and Laura used a solar simulator in the lab to investigate this further. Using filters, they can block out different wavelengths of light, focussing what the selected light on the skin cells happily growing in their dishes. They explored 5 different combinations of light: Vis only, Vis and IR, UV and Vis, UV only and a combination of all three. They explored the production of ROS and damage to nuclear and mitochondrial DNA as a result.

What they found out

What they found was quite surprising. When they looked at cells from the epidermis (the top layer), there was an increase in ROS production with UV only and a similar increase with total solar light (68% and 76% more production). The dermis cells had a slight increase in ROS production again with UV only (44% increase), but a large and synergistic effect from all three together (a whopping 158% more!) This effect was then shown in both nuclear and mitochondrial DNA damage too. Finally, the longer the epidermal cells were exposed to these 3 groups, the greater the difference between UV only and UV + Vis + IR. As you reach the equivalent of 4 hours in the sun, the total solar light starts to similar a combined stress as it does on the dermal cells.

In a nutshell

This study showed that skin cells from the epidermis and the dermis both have different damage responses to solar light. Dermal cells are less resistant to Vis and IR light. Epidermal keratinocytes have extra protection against this (which is good because they get hit first!). Overall, maybe we need to start thinking about protecting against all light if we are sitting out for extended periods of time!

Skin vs Urban Dust

Pollution gets under your skin

Pollution has been in the news a lot recently. It is guilty of affecting your lungs, heart, eyes, kidneys.. it’s pretty bad stuff. But what is it doing to your skin?

Skin really does have a lot of responsibility; it has to keep the environment out. Every day it is bombarded with pathogens, sunlight, the weather, and of course pollution. Particulate matter comes in all shapes and sizes, encompassing the mixture of tiny particles and liquid droplets. They can either get into the skin and cause direct damage or carry other harmful compounds to the skin. Again, we see a resulting production of reactive oxygen species (ROS) as the leading culprit in the observed damage. What exactly does particulate matter do to the skin? Wil Reynolds took a closer look at this, specifically how pollution might cause skin ageing.

What they found

Urban dust particulate matter (PM) was prepared to add to the dermal skin cells. The damaging effects were assessed through metabolic rate, DNA damage and proteins that alter skin structure. As they increased the concentration of PM, the cells appeared to grow faster and look thin and spindly. PM was also found to active the AhR receptor, thought to have evolved to help us tolerate fire smoke, it helps eliminate a range of toxins but also produce ROS in return. The greater the concentration of PM, the more AhR activation. So PM is activating this toxin response. Next, they found that there is dose dependant damage to nuclear DNA. As they increased the concentration, they found more breaks in the DNA. Even worse, this urban dust is toxic and its breaks our DNA (yikes!)

The effect of PM on matrix metalloproteases (MMPs) was then investigated. MMPs can be produced in response to stress, but also breaks down collagen in our skin leading to wrinkles. They found a direct relationship between PM and the increased production of MMPs. Next, they measured TGFβ, a key protein which can increase collagen production. The same relationship was found, the higher the concentration of PM, the greater the increase in TGFβ. All great right? MMPs break down collagen and TGFβ to the rescue! Unfortunately, this might not be the case. They took this further and looked at the effects over the course of a week; each day the MMPs go up and up, and each day the TGFβ goes down.

In a nutshell

Pollution in the form of particulate matter is toxic. It damages our DNA and increases the likelihood of cell senescence (becoming inactive), leading to skin ageing. Exposure to PM produces collagen degrading proteins causing wrinkles, and prolonged exposure aggravates this damage. It appears there needs to be more skin ageing research to help prevent pollution effects skin.

Niacinamide, the mitochondrial fountain of youth

Now we have discussed the damaging effects of solar light and pollution on the skin, we have products to protect against this. Unfortunately, no matter how hard we try our skin will inevitably get damaged, and our mitochondrial batteries start to wear out.

What exactly is happening to our mitochondria as we age? And what can we do to fix it? Niacinamide (vitamin B3) has been hailed as a skin barrier fixing, anti-ageing, pigmentation regulating, wrinkle reducing, sensitivity reducing, acne saving miracle ingredient. Dr Amy Bowman’s work contributed to this study, looking at the effects of niacinamide on mitochondrial function.

What they found

In the genes

First, the team investigates mitochondrial function in ageing skin. They did this by looking at gene expression, by which your genetic code is made into a functional product (proteins and RNA). In skin biopsies taken from people in their 20s-70s, they found a reduction of mitochondrial building blocks as age increase. Next, they demonstrated that this effect was also seen in young and old cell grown in the lab (dermal fibroblasts). After treating cells for 7 days with niacinamide, the level of these mitochondrial building blocks increased, as did the mitochondrial activity. Therefore, niacinamide helps to improve mitochondrial function.

Assessing the function

So the mitochondrial function increases after treatment with niacinamide, but this needed to be investigated further to understand the differences between young and old skin cells. This was done using a Seahorse Analyzer, which you could describe as a mitochondrial treadmill. Mitochondria are pushed to their limits, and different parts of their machinery are blocked to see how well they can cope with stress. Young skin cells are much more resilient than old cells. they start off with greater activity and are not as affected by the stress. When the old cells were treated with niacinamide, they found their mitochondria functioning to a similar level of the young mitochondria at each stage of the test. So niacinamide can make old mitochondria young again!

Under the microscope

Can this been seen with our eyes? Yes! …if you have a microscope and some fancy staining equipment… Imaging experiments found that there was more mitochondria and they looked healthier when treated with niacinamide, both young and old. Lastly they investigated mitophagy, a process in which the cell recycles dysfunctional mitochondria. Younger cells undergo more mitophagy than older cells, and both the younger and the older cells underwent more mitophagy when treated with niacinamide. So niacinamide helps cells get rid of bad mitochondria that can cause further damage to the cell if left unchecked.

In a nutshell

Young cells have better functioning mitochondria that older cells. Niacinamide can make the mitochondria in older cells function like young cells again, increase the amount of mitochondria in the cell and get rid of damaged mitochondria. Basically a mitochondrial fountain of youth! Seems pretty good to me, a major win for skin ageing research.