Collagen synthesis: should cosmetics target keratinocytes rather than fibroblasts?

Collagen synthesis: should cosmetics target keratinocytes rather than fibroblasts?

The quest for firm, smooth, weather-resistant skin relies heavily on maintaining optimal collagen production. This structural protein, which makes up the majority of the dermis, ensures skin elasticity and cohesion. Traditionally, dermal fibroblasts are considered to be the key players in collagen synthesis, and many cosmetic approaches aim to stimulate their activity.

Yet recent research suggests that keratinocytes - the epidermis' dominant cells - play a decisive role in regulating this process. This discovery raises a strategic question: to effectively stimulate collagen synthesis, shouldn't we be targeting keratinocytes rather than fibroblasts themselves?

1. Collagen: essential architecture

Collagen accounts for some 70-80% of dermal proteins. Its thick fibers form a mesh that gives the skin its mechanical strength and suppleness. With age,sun exposure, pollution or oxidative stress, collagen production declines, while its degradation accelerates, causing wrinkles, sagging and loss of tone.

The main aim of anti-aging skincare is therefore twofold: to stimulate collagen neosynthesis and slow down its enzymatic degradation (by matrix metalloproteinases, MMPs).

2. Fibroblasts: the architects of the dermis

Fibroblasts reside in the dermis, just beneath the epidermis. They produce collagen, elastin and glycosaminoglycans (notably hyaluronic acid). For decades, the majority of cosmetic research and formulations have focused on the direct stimulation of these cells.

For example:

  • Retinoids (vitamin A and derivatives) activate the expression of genes linked to collagen production and inhibit certain MMPs.

  • Biomimetic peptides mimic natural collagen fragments to "alert" fibroblasts and boost production.

  • Vitamin C acts as an essential cofactor in the stabilization of the collagen triple helix and enhances fibroblast activity.

However, a major obstacle remains: the majority of cosmetic ingredients only penetrate the dermis with difficulty. The cutaneous barrier limits their diffusion, thus reducing their direct effectiveness on fibroblasts.

3. Keratinocytes: simple epidermal building blocks?

Keratinocytes make up around 90% of epidermal cells. Their best-known role is to form the skin's protective barrier, thanks to the keratin and lipids they produce. But these cells are more than just passive "building blocks": they constantly communicate with fibroblasts via biochemical signals (growth factors, cytokines, peptides).

In this way, keratinocytes can indirectly influence fibroblast activity and thus collagen synthesis. This "epidermis → dermis" communication pathway is sometimes more accessible to cosmetics, since ingredients applied to the skin first reach the keratinocytes.

4. Epidermis-dermis communication mechanisms

Several mediators released by keratinocytes play a key role in collagen regulation:

  • TGF-β (Transforming Growth Factor-β): one of the most powerful signals for activating fibroblasts and stimulating collagen synthesis. Keratinocytes can secrete TGF-β in response to certain stimuli.

  • Interleukins and cytokines: modulators of inflammation, they influence the expression of MMPs and thus collagen degradation.

  • Growth factors (EGF, KGF, VEGF): promote cell proliferation and wound healing, a process in which collagen production is essential.

Thus, targeting keratinocytes could trigger a cascade of beneficial events, indirectly but effectively stimulating fibroblasts.

5. Emerging scientific evidence

In vitro and ex vivo studies have shown that :

  • Plant extracts applied to keratinocytes increase TGF-β secretion, leading to increased collagen production by neighboring fibroblasts.

  • By protecting keratinocytes from oxidative stress, certain antioxidant molecules maintain their ability to positively regulate fibroblast activity.

  • Signal peptides interact with keratinocytes to trigger the release of factors capable of amplifying extracellular matrix synthesis in the dermis.

These results suggest that the epidermis is a more realistic and strategic target for anti-aging cosmetics than the deep dermis.

6. The advantages of a keratinocyte-focused strategy

  1. Accessibility: Keratinocytes are directly exposed to surface-applied ingredients, unlike fibroblasts located deeper down.

  2. Cascade effect: a small stimulus on keratinocytes can trigger an amplified response in the dermis via powerful mediators.

  3. Synergy: Keratinocytes are also involved in antioxidant and immune protection, two factors that indirectly influence collagen preservation.

  4. Innovation: Cosmetics could be renewed by exploiting this little-explored communication channel, opening the way to new active ingredients.

7. Limits and precautions

Targeting keratinocytes is not without its challenges:

  • The signals sent by keratinocytes can be ambivalent: some promote collagen synthesis, while others stimulate inflammation and degradation.

  • Over-stimulation can upset the skin's equilibrium, leading to undesirable reactions (redness, sensitivity).

  • Clinical evidence is still lacking to confirm that these mechanisms observed in the laboratory translate into visible benefits on human skin over the long term.

8. Emerging cosmetics approaches

Several avenues are currently being explored:

  • Epidermis-dermis peptides: designed to specifically activate keratinocytes and trigger TGF-β secretion.

  • New-generation antioxidants: capable of protecting keratinocyte DNA and mitochondria to preserve their regulatory role.

  • Pre- and postbiotics: by modulating the skin microbiome, they influence the health of keratinocytes and their communication with the dermis.

  • Keratinocyte-derived exosomes: natural signal vectors, they represent a promising but still experimental avenue.

9. Towards an integrated vision of anti-aging

The question of whether to target fibroblasts or keratinocytes does not necessarily imply an exclusive choice. Skin physiology is complex and relies on permanent interactions between its different layers. An optimal strategy might combine :

  • Direct stimulation of fibroblasts by penetrating active ingredients (retinoids, stabilized vitamin C).

  • Indirect regulation via the more accessible keratinocytes, which mediate biological activity.

  • Global protection of the skin environment (antioxidants, sun filters, anti-pollution).

Conclusion

Long considered the only players in collagen synthesis, fibroblasts are in fact only part of the equation. Although located on the surface, keratinocytes play a crucial regulatory role thanks to their ability to interact with the dermis. Targeting these epidermal cells appears not only more accessible for topical cosmetics, but also potentially more effective thanks to the cascade effect of the mediators they secrete.

Nevertheless, caution is still called for: scientific knowledge needs to be consolidated by robust clinical studies, and the regulation of keratinocyte signals needs to be finely dosed to avoid undesirable effects.

In the future, cosmetic anti-aging could evolve towards a more systemic approach, integrating all cellular communications rather than focusing solely on the traditional target of fibroblasts. Keratinocytes, long perceived as mere "building blocks" of the epidermis, could well become the true conductors of skin youthfulness.

Back to blog