Deep Guide to Collagen - ways to preserve and boost collagen in your skin

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What is collagen (and the ECM)?

We hear about collagen in many contexts, and that is because collagen is the main structural protein in your body. Collagen is part of your tendons, ligaments, cartilage, bone, blood vessels, and of course, your skin.

Collagen is referred to as a "structural protein" because it is firm and gives structure to the body. It acts like scaffolding, providing support and shape to tissues.

There are many different types of proteins in the human body, each with a specific function:

So what are all these collagen proteins in your skin doing? Basically, they are forming a scaffold and holding up the skin. That is why as you age and you lose collagen, your skin sags and you develop lines and wrinkles.

As you age, you also lose another protein called elastin which gives your skin elasticity and bounciness. Both collagen and elastin are found in the dermal layer of your skin — the layer underneath your epidermis.

The epidermis is that visible outer layer of your skin, and though you can see the lines and wrinkles from the outside, you have to go to the invisible dermal layer where collagen is located to fix the problem.

Collagen is secreted by dermal cells called fibroblasts to form something called the extracellular matrix (abbreviated as ECM). Extracellular means outside cells. The ECM is a matrix of collagen and other proteins such as elastin that are outside of cells and that form a thick scaffold around your dermal cells.

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Different types of collagen and their functions

Now we are going to go further in depth here, and talk a little bit about collagen types in your skin, mainly because this will help you understand scientific findings related to collagen.

When we talk about collagen in reference to skin, we are mostly referring to type 1 collagen, which makes up 80% of the collagen fibrils in young adult skin, and to a lesser extent, type 3 collagen which co-polymerizes with type 1 collagen to make up about 15% (Kular et al. 2014).

Type 1 and Type 3 collagen are types of collagen that can form long fibrils that provide support structure (Wang 2021). In the figure below, you can see an electron microscope image of what these collagen support structures look like:

These fibrils assemble into dense and compact bundles forming thick, regular fibers. These bundles connect to each other at various points due to interlacing, and these bundles increase in size the deeper you go in the dermis (Thakur et al. 2008).

These fibrils are anchored to the basement membrane located between the dermis and epidermis, and then cells and macromolecules can anchor themselves to this collagen fibril scaffold. This is how collagen gives your skin its shape and also organizes the various components of the dermis.

The basement membrane that is in between your dermis and your epidermis is mostly made up of Type 4 collagen which forms networks (sheets) rather than long fibrils (van der Rest and Garrone 1991, Bosman and Stamenkovic 2003). Type 5 and Type 6 collagens may also be found in the dermis and may play roles in cell migration and matrix assembly, while Type 7 collagen is a predominant component of anchoring fibrils between the Type 4 collagen in the basement membrane and the upper dermis (Uitto et al. 1989).

So, what we commonly call "collagen" is actually collagen fibers — think of this as the finished product. To be more precise, what is made by fibroblasts is procollagen. Procollagen is where it all starts.

What the heck is procollagen? So when you hear "pro-something" in a biology context it usually means a precursor, a building block, to that something. Like — you can say eggs are pro-omelet. Because omelet is made from eggs. Likewise, collagen is made from procollagen. You might see procollagen also referred to as collagen peptides. That's because collagen is protein, and peptides are fragments of protein.

Procollagen looks like a loose, single strand string:

As a next step, enzymes take these loose strands of procollagen and braid them into collagen molecules. A finished collagen molecule is 3 procollagen strands braided together in a form called triple-helix. And once the braiding is done the ends are neatly trimmed off.

Once we have a bunch of collagen molecules, they can be crosslinked together to form what's called "fibrils." And then when you bundle a bunch of collagen fibrils together you get collagen fibers.

And here is a picture taken from the skin of a younger person between 18 and 29. This image is showing a cross-sectional slice.

So we just went over the collagen building process: procollagen → collagen molecules → fibrils → fibers. You want healthy, intact, strong collagen fibers because healthy collagen fibers give firmness to the skin and prevent sagging.

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Elastin and glycosaminoglycans (GAGs)

This is a good place to mention another protein that's also critical for maintaining beautiful skin: elastin. Elastin doesn't get anywhere near as many mentions as collagen, but it's really important for our skin so it's worth covering briefly here.

Elastin is a protein — like collagen — and it is responsible for providing elasticity and resilience to the skin, which allows it to stretch and move while retaining its shape. Think of elastin like lycra in your jeans. It is a stretchy protein that forms a randomly oriented, interconnected fiber network that can rapidly recoil after being mechanically stretched. Though elastin content in normal adult skin is only about 2–4% of its dry weight, it is important for skin's elasticity and stretchiness (Uitto et al. 1989).

This is what elastin fibers look like under an electron microscope — it's like stretchy netting. If you think of collagen like the sticks in an Erector set that kids play with, then elastin is like the rubber bands that hold the parts together so they can flex and move.

In addition to collagen and elastin, the third component of the ECM is the glycosaminoglycan/proteoglycan macromolecules that account for 0.1–0.3% of the dry weight of the dermis (Thakur et al. 2008). The most common glycosaminoglycans (GAGs) in the skin are hyaluronic acid and dermatan sulfate. GAGs and proteoglycans can bind a volume of water in the dermis up to 1,000 times the size of the molecule itself! (Thakur et al. 2008). These play a role in maintaining skin hydration and turgor as well as transport of water-soluble nutritional material in the ECM.

In addition to collagen and elastin, fibroblasts also secrete GAGs and proteoglycans. Hence, again, generally speaking, what's good for collagen production is often also good for production of these hygroscopic GAGs.

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How aging affects the ECM

In aging, your dermal fibroblasts produce less and less collagen. For example, Varani et al. 2006 found that fibroblasts from older skin produced two thirds less Type 1 procollagen than those from younger skin.

Further, as you age, even the collagen that you do have left gets more degraded and broken up and so it isn't in an intact form.

Going back to an image we saw earlier of collagen and fibroblast from younger skin, when compared against older skin, it is noticeable that in older skin, collagen fibers are sparse and spotty. You don't see that extensive netting made up of collagen fibers anymore.

Fibroblasts are attached and anchored to the collagen fibers — like a rock climber holding onto a cliff with all his limbs. Fibroblasts need that mechanical tension of being physically anchored to collagen fibers to optimally function and produce procollagen. However, in older skin, as collagen deteriorates the fibroblasts become unmoored. Basically, fibroblasts just float around in older skin.

This lack of anchoring also makes the fibroblast produce less procollagen as explained in this illustration from Varani and colleagues.

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MMPs and collagenases

So — why is collagen less able to stay intact as we age? What causes collagen to break down as we get older?

The culprit in this case is enzymes called matrix metalloproteinases or MMPs. And to be more precise, it's uncontrolled overactivity of MMPs that leads to breakdown of collagen. MMPs are a type of protease, which means they are proteins that can break down other proteins.

In younger skin, the activities of MMPs are well controlled. MMPs are NOT bad for you — they're actually quite essential for maintaining our health because MMPs are used for wound healing, basically purging damaged skin so new skin can grow. Think of MMPs like wrecking crews that have to come in and knock down walls when you do house remodeling.

MMPs that break down collagen can also be referred to as collagenases, which are a subset of MMPs (MMP-1, 8, 13). Other MMPs are involved in the degradation of other ECM proteins, such as elastin and proteoglycans. Further, MMPs often are nonspecific and can break down many different components of the ECM (Bosman and Stamenkovic, 2003).

MMPs are regulated by a number of different mechanisms, including the action of other enzymes, hormones, and growth factors.

In older skin, things don't work as well as they should and MMPs go a little haywire. The amounts of MMPs become overly elevated — there are more MMPs than needed — and excess MMPs turn on us and start to attack the healthy collagen and break them up. Specifically, levels of MMPs including MMP-1, MMP-9, and MMP-2 were found to be elevated by 40, 52, and 82 percent respectively in the 80+ age group as compared to the 18–29 age group (Thakur et al. 2008).

Why does this happen? It could be an immune system gone awry. Your mast cells — immune cells that handle inflammation and MMP secretion — become more activated by innate mechanisms (Thakur et al. 2008). As you age, you lose cellular integrity and you generate more reactive oxygenated species (ROS). Remember that UV exposure can also lead to ROS generation.

These ROS are like bullets that rip through your skin tissue and destroy collagen, elastin, and DNA. The cell damage from ROS leads to production of prostaglandins and leukotrienes, part of your immune system. This leads to inflammation via mast cell activation, and the release of histamine and other inflammatory molecules which recruit more immune cells that release MMPs. Mast cells also release MMPs, releasing more prostaglandins and leukotrienes to promote even more inflammation — and even more MMPs.

The picture with elastin is slightly more complicated than with collagen. Photoaging seemingly has the opposite effect as intrinsic aging in that UV exposure triggers fibroblasts to make excessive amounts of elastin. While this might seem like a good thing, the elastin that is secreted in this manner does not form functional elastic fibers. Think zombies or mutants — this type of elastin may be up and running but it just isn't right.

Instead, this UV-induced elastin forms aberrant elastotic material that leads to a condition called solar elastosis, which manifests as yellow, thickened, coarsely wrinkled skin:

Interestingly, treatments like retinoids that enhance dermal collagen can lead to replacement of the elastotic material, leading to repair of the condition (Uitto et al. 1989). Hence, increasing collagen affects other positive changes on other components of the ECM, such as elastin.

Further, as aging progresses, dermal fibroblasts also secrete less hyaluronic acid and other GAGs, which erodes the water retaining capacity of the skin, further resulting in a dried and wrinkled appearance in aged skin (Thakur et al. 2008). Hence, another aim of stimulating fibroblasts — beyond increasing collagen synthesis — is the increase in GAGs. Retinoids which increase collagen also increase GAGs.

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3 strategies to boost collagen

Let's now focus on how you can boost levels of collagen to help return your skin to its more vibrant state (remember that boosting collagen can also lead to boosts in elastin and GAGs as well).

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Ingredients that can boost collagen

Vitamin C

First, let's start with Vitamin C. Vitamin C is sort of a superstar ingredient in skincare and — like many things — Vitamin C levels decrease in your skin as you age irrespective of diet.

Click here to read Maelove's Deep Guide to Vitamin C

Vitamin C is one of the main antioxidants in your skin and the decline in Vitamin C in your skin leaves you with less protection against UV and free radical damage. Another implication is that less collagen is synthesized in your skin.

Vitamin C is a required cofactor for enzymes that allow procollagen peptides to form the triple helix conformation seen in collagen fibrils. Further, the presence of ascorbic acid spurs the synthesis of type 1 and type 3 procollagen peptides (Uitto et al. 1989). Hence, a decrease in ascorbic acid in the skin with age can contribute to the decline in collagen.

The good news is that studies suggest topical application of Vitamin C serums can partially reverse this trend. Specifically, Nusgens and colleagues found that Vitamin C:

Skin benefits have been demonstrated in placebo-controlled studies of intrinsically aged skin in postmenopausal women (Nusgens et al. 2001) as well as photo-damaged skin (Traikovitch 1999), with improvements noted in fine wrinkling, tactile roughness, coarse rhytids, skin laxity/tone, and sallowness/yellowing.

Retinoids (Vitamin A and Vitamin A derivatives)

Click here to read Maelove's Deep Guide to Retinoids

Click here to read Retinol vs Retinaldehyde (Retinal)

Retinoids are Vitamin A itself or Vitamin A derivatives. Irrespective of the retinoid you use, if it is effective — as in the case of retinol, retinal, or tretinoin — it all gets converted into retinoic acid inside the skin cell where it has its effects. So all retinoids work via retinoic acid receptors.

If you are interested in anti-aging, you will definitely want a retinoid in your skincare regime. Retinoids will get into the nucleus of your skin cells and kick off a host of processes that include stimulating keratinocytes so that your epidermis thickens, increasing endothelial proliferation so that you will have better dermal vascularity and improved blood flow to the skin, and — of course — increasing collagen production (Shao et al. 2017).

Shao and colleagues also found that application of retinoids resulted in a four fold increase in elastin, shown in the red stain below.

You can also see in the following figure that not only is collagen content increased with retinoid treatment, but more collagen is preserved and intact. This is likely due to inhibition of MMPs by retinoids. Collagen fibers look more intact and in the 3-dimensional image the collagen fibers are interconnected with each other with more cohesive, smoother surfaces. Quantified, there was a 48% difference between the control and retinoid groups.

These benefits have been replicated in other high quality studies. For example, this figure from Kong and colleagues' 2015 study showed increases in gene expression for Type 1 and Type 3 procollagen with retinol and retinoic acid compared to vehicle treatment.

Overall, all these changes translate into measurable decreases in fine lines and wrinkles and result in a firmer, smoother, more bouncy skin. These changes are dramatic. For example, Kong et al. found up to 39% reduction in eye area wrinkles and 64% reduction in cheek area wrinkles after 12 weeks of treatment with 0.1% retinol.

There has been a large number of studies that demonstrate the effectiveness of retinoids in improving the conditions of both naturally aged and photo-damaged skin. It improves elastin and GAG levels as well as collagen levels. That's why retinoids are your dermatologist's favorite anti-aging ingredient.

So which retinoid should you use? We recommend either retinol or retinaldehyde — they're both available without prescription. At Maelove, our favorite is retinaldehyde (also known as retinal with an A). It's as potent as prescription retinoids like tretinoin but you can get it without a prescription, and it's also less irritating than tretinoin.

Niacinamide (Vitamin B3)

You might have heard that niacinamide is amazing for strengthening the skin barrier. Here is how that works:

Click here to read Maelove's Deep Guide to Niacinamide

Once absorbed into the skin, niacinamide gets converted into NAD and NADP (nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate). Similar to Vitamin C, the levels of NAD and NADP in the skin naturally decline with aging. These cofactors are critical for cell metabolism, and so as the levels drop, your cells are less able to synthesize the lipids and proteins that help form the skin barrier, resulting in dry, scaly skin.

Topical supplementation with niacinamide has been shown to raise NAD and NADP levels in the skin, and lead to an increased synthesis of lipids (ceramides, free fatty acids, and cholesterol) and proteins — including keratin, filaggrin, involucrin, and — you guessed it — collagen. This leads to improved fine lines and wrinkles as well as improved skin texture (Matts et al. 2002).

So, niacinamide is another do-it-all ingredient, much like Vitamin C and retinoids.

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What skincare products to look for to boost collagen

Our 3 favorite ingredients for boosting collagen are Vitamin C, retinoids, and niacinamide. In terms of products you'd actually buy:

There are some other ingredients that show evidence of boosting collagen — generally less proven, but worth mentioning:

That's it! Thanks for reading. Don't forget to check out our other newsletters.

—Team Maelove

Written by our senior scientist Sunbin Song, PhD, and edited for clarity by Bradley Yim, our Head of Formulation. You can read more about them on our Team Page.