Coined by Franceschi et al. in 2000, inflammaging describes the chronic, low-grade inflammation that increases with age and contributes to age-related diseases. The World Health Organization World Report on Aging and Health (2015) recognized the importance of strategies for healthy aging, and how skin health plays a central role in this conversation (although often overlooked).
Our skin is constantly exposed to both internal and external stressors – from UV radiation and pollution to microbial challenges. Over time, these stressors trigger a state of persistent, subclinical inflammation that accelerates visible signs of aging: wrinkles, uneven textures, slower regeneration and a weakened barrier.
At the molecular level, inflammaging involves a complex network of biological processes, including mitochondrial dysfunction, excessive reactive oxygen species (ROS), inflammasome activation, and the release of pro-inflammatory cytokines such as IL-1, IL-6, IL-8, and TNF-α. These pathways stimulate matrix metalloproteinases (MMPs) and the senescence-associated secretary phenotype (SASP), driving tissue degradation and impaired repair mechanisms.
Addressing these interconnected processes requires actives that go beyond surface-level effects. bitop Ectoin® natural has been shown to counteract several key mechanisms of skin inflammaging, helping to protect cells, stabilize membranes, and support long-term skin resilience.
In the sections ahead, we’ll take a closer look at how these actives work across these biological pathways and why they’re emerging as a cornerstone ingredient in skin longevity formulations.
Figure 1 : Schematic network connecting senescence/immunosenescence, inflammaging, frailty, and age-related diseases.
Inflammaging doesn’t happen overnight, it’s a gradual shift in how our cells communicate and respond to stress. As we age, the body’s fine-tuned balance between repair and defense begins to blur, leading to a state of ongoing, low-level inflammation that silently drives visible and structural changes in the skin.
Figure 2: Imbalance of Macrophages leading to Inflammaging
Figure 3: A model proposed to explain the mechanism of inflammaging in skin
Researchers have identified five distinct yet overlapping states of inflammaging: low-grade, controlled, asymptomatic, chronic, and systemic[2]. Together, these reflect how the body transitions from protective inflammation to one that becomes self-sustaining. These states arise from intricate interactions between cells and their surrounding microenvironment – a delicate balance of physiological and pathological signaling networks that, when disrupted, set the stage for chronic tissue stress and dysfunction.
Emerging research points to several interconnected biological mechanisms that drive inflammaging. While they operate through different pathways, all converge on the same outcome: cellular senescence, chronic inflammation, and progressive decline in tissue function.
Compromised Barrier Integrity
Oxidative Stress
Cytokine Dysregulation
Inflammatory Cascade Activation
Among all the drivers of inflammaging, cytokines remain a focal point in current research. Their dual role, as both regulator and biomarker of inflammation, makes them essential for understanding and ultimately mitigating the effects of aging[5]. Aging studies show that a healthy balance of pro and anti-inflammatory cytokine secretion is associated with successful aging whereas dysregulation of this system results in inflammaging, poor aging phenotypes, and other aging related diseases [7]. Currently, levels of TNF-a, IL-6 and IL-1 can be used as inflammatory biomarkers that indicate frailty, an altered immune system, functional decline and mortality associated with inflammaging [10].
Ectoin® natural by bitop is a stress-protective cyclic amino acid known for its remarkable ability to stabilize and protect cells under extreme environmental conditions. In skincare, this translates into powerful protection for cellular structures and essential biomolecules against both internal and external stressors.
Its anti-inflammaging activity follows a threefold mode of action, addressing inflammation at every stage – from prevention and modulation to resolution and repair. By intervening early and supporting skin’s natural recovery processes, this active helps maintain homeostasis, resilience, and long-term skin health.
1. Prevention of Inflammation: Cellular Protection and Membrane Stabilization:
Ectoin® natural acts as a molecular shield, forming a protective water shell around cellular structures through its unique compatible solute mechanism. This hydration shell stabilizes cell membranes, lipids, and proteins, thereby:
2. Treatment of Existing Inflammation: Cytokine and Pathway Modulation:
Ectoin® exerts a potent immunomodulatory effect, attenuating the inflammatory cascade by:
These combined effects interrupt the vicious cycle of chronic inflammation, mitigating tissue damage and slowing the progression of inflammaging.
3. Promotion of Repair: Barrier Restoration, Hydration, Skin Regeneration:
Beyond anti-inflammatory effects, Ectoin® enhances skin barrier integrity and supports regenerative processes by:
In a double-blind, randomized, placebo-controlled clinical study the test products were a cream containing 1% Ectoin® natural, control (0.25% Hydrocortisone) “Ebenol® Cream“, placebo cream
1% Ectoin® natural reduced the TEWL by 24% and skin redness by 38% after only 7 days of treatment, due to its anti-inflammatory and repairing properties.
The efficacy of 1% Ectoin® natural was equivalent or even better than the results of the treatment with Ebenol®, proving its “Hydrocortisone-like” efficacy.
Figure 6: Average values of skin redness
Furthermore, a recent in vivo clinical study also proved the short-term anti-inflammatory efficacy of Ectoin® natural.
Single application of 0.5% Ectoin® natural is clinically proven to strengthen the skin barrier within 4 hours, with a reduction of TEWL and skin irritation by 60%.
0.5% Ectoin® natural also demonstrates long-term skin barrier and skin-soothing efficacy upto 48 hours (single application) with a reduction of TEWL by 72%.
The efficacy of Ectoin® in downregulating cytokines, interleukins and TNF- α has been proven with two clinical trials. The first clinical trial was conducted on patients suffering from chronic lung inflammation and the second clinical trial was conducted on patients suffering from Chemotherapy-induced Oral Mucositis.
Both these clinical trials have demonstrated that Ectoin® down-regulates the expression of key inflammatory mediators, particularly:
Ectoin® effectively modulates inflammatory cytokines and interleukins (TNF-α, IL-1β, IL-6, IL-8), thereby showing excellent efficacy and tolerability for clinical use.
In the evolving field of skin longevity, Ectoin® natural stands out as a clinically proven bioactive that tackles inflammaging at its roots. By addressing cytokine overexpression, oxidative stress, and impaired barrier function, it restores balance where ageing begins – at the cellular level.
Clinical studies show significant downregulation in key pro-inflammatory cytokines, IL-1α (↓30%), IL-6 (↓50%), IL-8 (↓45%), and TNF-α (↓40%), effectively interrupting the cycle of chronic low-grade inflammation that accelerates skin ageing. In both short and long-term in vivo studies, Ectoin® improved hydration, reduced erythema, and enhanced integrity. All while delivering efficacy comparable to hydrocortisone, but with higher safety and tolerability.
At the molecular level, Ectoin® inhibit NF-kB activation, modulates MAPK signaling, and mitigates ROS accumulation, protecting keratinocytes from premature senescence. Its threefold mechanism – prevention, treat and repair – supports cytokine homeostasis, reinforces the skin barrier, and promotes long-term regeneration.
Together, these effects establish Ectoin® natural as a next-generation bioactive for maintaining skin health, resilience and longevity. It bridges the gap between cosmetic innovation and therapeutic science.
Interested in exploring Ectoin® natural for your formulations? Request your sample today on Covalo, and experience how this molecule can power your next innovation.
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