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Oxidative damage isn’t just caused by UV rays and doesn’t just cause photoaging. In fact, it even plays a role in inflammatory skin disorders like acne. I think this is an important topic and I’m going to do my best to keep it simple and not too complicated… but this is definitely a science heavy topic.
What are reactive oxidative species, what is their function in the skin, and how do they become destructive?
This section is going to be the more science-y part but stick with me, the basics are important in understanding the more interesting parts that come after.
ROS, or what you may have heard called “free radicals,” are derived from oxygen and occur in all aerobic species. See how oxygen in the image above has a single dot on each side where all its other dots are in sets of twos? These represent its electrons and because it has two unpaired electrons, it’s highly susceptible to radical formation. You can see how in the other structures after oxygen, all those reactive oxygen species are formed by adding electrons and/or hydrogen to oxygen.
ROS formation typically occurs as a by-product of mitochondrial oxidative metabolism but can also be generated as a cellular response to things like microbial invasion, UV radiation, and metal catalysis. It’s important to understand that they’re not inherently bad. Low levels function as important signaling molecules for physiological processes and they serve important functions in the skin especially. But because they’re unstable molecules that react with other molecules, excess levels can damage our DNA, protein, and lipids which is when they became a concern.
I think most of us have heard of free radicals and how they’re damaging. But the average person may not understand all the important functions that they serve so I want to briefly touch on a few here.
High levels of ROS are generated during the inflammation phase of the wound healing cascade and are key in destroying invading microorganisms and/or removing damaged tissue from the site of the injury. Low levels serve other important functions too like both increasing and decreasing skin pigmentation.
Speaking of which, melanocytes (pigment producing cells) are more susceptible to oxidative damage because they generate more free radicals than other skin cells like keratinocytes and due to melanogenesis (pigment formation) are under constant oxidative stress while having lower repair capacity. ROS also play an important role in regards to skin lipids, particularly sebum. UV generated ROS actually stimulate the sebaceous (oil) glands to produce more sebum and moisturize the skin and lipid peroxidation plays a role in wound healing.
The issue with reactive oxidative species is when high levels are generated and they aren’t balanced out by antioxidant defenses – which then leads to oxidative damage and alteration to structures of protein, lipids, and DNA. Luckily though, since ROS are by-products of normal cell activity, the body has developed its own defenses against them.
There are 4 primary antioxidant mechanisms of defending against free radicals:
- sequestration of transition metal ions
- scavenging of ROS
- ending of chain reactions ROS
- molecular repairing of oxidative damage
And some of the antioxidants involved in this defense are:
- Glutathione and Glutathione peroxidase (they work differently)
- Alpha Lipoic Acid
- Coenzyme Q
- Superoxide Dismutase
Oxidative Damage and its Impact on the Skin
Okay, now that we’ve covered the basics we can get into the real topic here: the role of ROS and oxidative damage in not just aging but skin disorders.
ROS generated by both extrinsic sources (like UV radiation) and intrinsic ones (oxidative metabolism) play a role in skin aging. They damage the extracellular matrix (ECM), particularly collagen, and this weakens not only the structural integrity of the skin but its function too.
As you can see represented in the image above, damage to collagen fibrils means that cells can’t spread normally which then decreases the size of our fibroblasts. This actually leads to more ROS being generated too so it only reinforces what we don’t want occurring. The other part of this is that in addition to degradation of dermal tissue like collagen, this also inhibits TGF-beta. This particular growth factor has many important functions that are mainly related to tissue development and maintaining them – and as a result, disrupting that pathway has been linked to higher incidences of disease including tumors.
But what’s relevant here is that TGF-b is critical for collagen synthesis which means that if inhibited, new collagen isn’t being produced and inflammatory cytokines are released leading to an inflammatory dermal microenvironment (aka “inflammaging,” which you may have heard of).
Essentially, ROS is responsible for the main characteristics we associate with aging skin.
Now we get to discuss a topic that I never really see discussed. Oxidative damage is almost always always left out of the equation when it comes to inflammatory skin disorders like acne or hyper pigmentation being discussed.
Our skin is under constant stress from its external environment. It’s got defenses to help manage ROS and when everything is in balance, levels are tightly regulated by our antioxidant systems. However, while very effective, these defenses can also be overwhelmed and that’s when we see oxidative damage occurring which can contribute to skin disorders.
Lipid peroxidation, as discussed above, is a big one when we look at oxidative damage and skin disorders. In regards to acne, there’s a lot we still don’t know as far as its pathogenesis. It was only recently that it was even designated an inflammatory disease – for a long time it was thought that there was inflammatory and non-inflammatory acne as well as a specific inflammatory stage. Now we know otherwise.
It was also initially believed that the clogged hair follicles and Propionibacterium acnes colonizing the pilosebaceous unit is what lead to inflammation and acne. Now we know that the first step in this process is a release of inflammatory chemicals. While we don’t know why acne patients have this inflammation, we do know that it goes hand in hand with the oxidation of sebum thanks to free radicals which alters the philosebaceous unit from a hostile environment for bacteria to the ideal one.
Older research even suggests that oxidized lipids may be comedogenic themselves and oxidized squalene was found to be higher in acne patients in one study. There were arguments for using antioxidants in acne patients back then too and some success even but unfortunately that research hasn’t been continued. It’s possible though that lipid peroxidation may come even before inflammation.
What about other skin disorders?
Absolutely. ROS both trigger and maintain skin inflammation and have been linked to other inflammatory disorders in addition to acne. Atopic dermatitis (eczema) and psoriasis have an inflammatory component for example and research has suggested that ROS plays a role.
This is also the case for rosacea:
“Rosacea is a common skin condition thought to be primarily an inflammatory disorder. Neutrophils, in particular, have been implicated in the inflammation associated with rosacea and mediate many of their effects through the release of reactive oxygen species. Recently, the role of reactive oxygen species in the pathophysiology of rosacea has been recognized. “ Source
It’s no wonder then that azelaic acid, which is both anti inflammatory and antioxidant, is so effective for rosacea.
Protecting Our Skin from Oxidative Damage
This leads us to the final part of this article. How do we protect our skin from elevated ROS levels and oxidative damage to lipids, protein, and DNA?
The biggest thing you can do is to wear a broad spectrum, high protection sunscreen and apply liberally and often. This will protect against the UV radiation that can generate free radicals. Second, you can use antioxidants both topically and orally. Always consult a medical provider if possible before taking taking supplements on your own, I am not a doctor. Sunscreen filters only protect against UV rays but antioxidants can educate ROS levels and oxidative stress as discussed previously.
In regards to topical antioxidants, look for a variety. Water soluble, fat soluble, and enzymatic antioxidants all protect differently. Fat-soluble antioxidants typical interact with free radicals inside cells while fat-soluble ones help with the cell membrane and preventing lipid peroxidation. Rooibos extract, (like in the Maysama Green Rooibos Pressed Serum linked below) has been shown to protect against lipid peroxidation where alpha lipoic acid can chelate free metals, acts as both a water and fat soluble antioxidant, and can even keep other antioxidants from oxidizing..
Whatever you choose, pick something with a wide array of antioxidants as they work synergistically together.
My favorite antioxidants:
- Maysama Green Rooibos Pressed Serum (code “mira10” to save)
- Skin Actives Vitamin C Serum 20%
- Skin Actives Antioxidant serum
But what about protecting the skin further against free radicals not generated from UV radiation? And repairing damage already done?
UV rays get a lot of attention and they are incredibly damaging – over 80% of photoaging is caused by sun damage. That being said, we’re finding out that other visible light can cause oxidative stress too and has been identified as a potential contributor to skin aging and melasma. And unfortunately, UV filters only protect against UV.
This is already too long so there’s no way I can go into further here. But I’ve been testing several products for a segment on sunscreens and serums that go beyond basic sun protection, whether it’s really promising antioxidants like the enzymatic ones that are part of our own defenses or iron oxides to protect against visible light. I’ve also been testing out DNA repair enzymes too so please stay tuned!
More coming soon and it will appeal to everyone not just the skincare science nerds hehe.
Sources and More Reading
Comment below what you found the most interesting part of the article or what you learned!