As we age, the skin gradually loses firmness and elasticity.
When it comes to this process, one term almost always comes up: collagen. And of course, collagen is crucial. But one point is surprisingly rarely mentioned:
Collagen not only needs to be formed, it also needs to be stably cross-linked.
Only through cross-links between individual collagen fibers do resilient structures form. Elastin also relies on such cross-links.¹ ²
And it is precisely at this point that a trace element comes into play that receives significantly less attention in connection with collagen: copper.
The enzyme behind stable collagen fibers
A key enzyme in this cross-linking process is called lysyl oxidase.
It alters certain building blocks of collagen and elastin, thereby enabling the formation of stable cross-links between the fibers.¹ ²
The crucial point: Lysyl oxidase is copper-dependent.
Copper is required for the activity of this enzyme. This gives the trace element a very specific role in connective tissue.
Copper is not itself a component of collagen. Rather, it is involved in an enzymatic process through which collagen and elastin fibers can be cross-linked and structurally stabilized.
The importance of this mechanism becomes particularly clear when copper metabolism is severely disrupted.
In people with a hereditary form of cutis laxa, lysyl oxidase activity in skin samples was only 13 to 26% of the normal value.³
At the same time, the researchers found fewer of the compounds that are formed during the cross-linking of collagen.³
This illustrates the connection: If the activity of copper-dependent lysyl oxidase decreases significantly, the structure of the connective tissue also changes.
Studies in people with Menkes syndrome, a rare inherited disorder of copper metabolism, also showed significantly reduced lysyl oxidase activity in skin fibroblasts.⁴
What happens when additional copper is added?
Also of interest in this context is a small placebo-controlled human study with young women.
Over eight weeks, eight participants received 2 mg of copper daily, while another eight received a placebo.⁵ Among other things, markers of collagen cross-linking were measured.
After eight weeks, the copper group showed a 62% increase in the ratio of certain collagen crosslinks to a measure of total collagen.⁵
This change was not observed in the placebo group.
The study was small, with a total of 16 participants. However, it shows that additional copper intake in humans can be associated with measurable changes in markers of collagen cross-linking.
Because with collagen, it's not just the quantity that matters. The crucial factor is also how the individual fibers are subsequently organized and cross-linked.
Copper has another interesting side
The same study also examined oxidative stress.
In the copper group, a marker for oxidative stress, so-called F₂-isoprostanes, decreased by an average of 39%.⁵
This finding leads to another biological function of copper.
Copper is a component of copper-zinc superoxide dismutase, or Cu/Zn-SOD for short.This enzyme is part of the antioxidant defense systems of our cells and is involved in the breakdown of reactive oxygen species.⁶
Thus, copper is encountered in the skin in two very different contexts: in the structural cross-linking of collagen and elastin, and as a component of the body's own antioxidant enzyme system.
Copper also plays a role in pigment formation.
Another copper-dependent enzyme is tyrosinase.
It catalyzes key steps in melanin formation.⁷ Melanin is the pigment that contributes significantly to the color of skin and hair and absorbs some of the incident UV radiation.
Tyrosinase also requires copper for its enzymatic activity.⁷
This means that the same trace element appears in the skin in several different locations:
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in the cross-linking of collagen and elastin
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as a component of antioxidant enzyme systems
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during the formation of melanin
Why a trace element is so interesting for collagen
When it comes to collagen, the focus is often on the formation of new collagen fibers.
But that's not the end of the story.
For collagen to fulfill its structural function in connective tissue, the individual fibers must be organized and stably cross-linked. A key enzyme in this process is lysyl oxidase, and this enzyme requires copper.¹ ²
At the same time, copper is involved in other enzymatic processes relevant to the skin. These include Cu/Zn superoxide dismutase as part of antioxidant defense systems and tyrosinase in melanin production.⁶ ⁷
Copper thus illustrates particularly clearly why even trace elements, which the body only needs in small amounts, can be involved in fundamental biological processes.
And why, when it comes to collagen, the crucial question is not just how much of it is present.
But also how a stable structure emerges from it.
Sources
¹ Rucker RB, Kosonen T, Clegg MS, et al. Copper, lysyl oxidase, and extracellular matrix protein cross-linking. American Journal of Clinical Nutrition. 1998;67(5 Suppl):996S–1002S.
² Vallet SD, Ricard-Blum S. Lysyl oxidases: from enzyme activity to extracellular matrix cross-links. Essays in Biochemistry. 2019;63(3):349–364.
³ Byers PH, Siegel RC, Holbrook KA, et al. X-linked cutis laxa: defective cross-link formation in collagen due to decreased lysyl oxidase activity. New England Journal of Medicine. 1980;303:61–65.
⁴ Royce PM, Camakaris J, Danks DM. Reduced lysyl oxidase activity in skin fibroblasts from patients with Menkes' syndrome. Biochemical Journal. 1980;192(2):579–586.
⁵ Milne DB, Nielsen FH. A pilot study of copper supplementation effects on plasma F2alpha isoprostanes and urinary collagen crosslinks in young adult women. Journal of Trace Elements in Medicine and Biology. 2010;24(3):165–170.
⁶ Fukai T, Ushio-Fukai M. Superoxide dismutases: role in redox signaling, vascular function, and diseases. Antioxidants & Redox signaling. 2011;15(6):1583–1606.
⁷ Olivares C, Solano F. New insights into the active site structure and catalytic mechanism of tyrosinase and its related proteins. Pigment Cell & Melanoma Research. 2009;22(6):750–760.