Dermal fibroblasts are essential for preserving the skin’s homoeostasis and viability. Their ability to contract affects ageing-related changes, particularly in the production of scar tissue, inflammation, wrinkles, and wound healing. It also involves extracellular matrix structural alterations. Although changes in skin physiology and morphology have been reported previously, there is still a lack of knowledge regarding how chronological ageing affects the contraction of dermal fibroblasts.

Researchers are still trying to fully grasp the intricate interactions that occur during the multifaceted skin ageing process. However, we are aware that both inherent and extrinsic aspects are involved. Skin atrophy, more prominent veins, decreased suppleness, and fine wrinkles are characteristics of intrinsic skin conditions, which are mostly genetically determined. Extrinsic factors, which are marked by fine lines and wrinkles, rough texture and abnormalities in pigmentation, include exposure to UV light and pollution. Type I and II skin exhibit enhanced extrinsic ageing in response to the same stimuli, while other skin types respond to extrinsic factors in various ways.

Oxidative Stress and Skin Ageing

The oxidative stress-induced age-related change of the collagen-rich extracellular matrix compromises the structural elasticity of the skin. It fosters age-related skin disorders such as slow wound healing and skin cancer. Disintegrated dermal fibroblasts in turn produce more ROS and cause more cellular oxidative stress, which is a significant factor in the ageing of connective tissue in the human skin.

Commonly used primary cells to study skin ageing

Using primary cells and cell models is another method for researching oxidative stress and ageing. They assist in providing the chance to comprehend the intricate intercellular communication that takes place between various cell types in the skin. Two-dimensional cell models cannot accurately represent these biological systems, necessitating three-dimensional methods. For instance, the coculture of many skin cell types in a three-dimensional matrix is possible in organotypic skin models.

Skin cell models can be employed to not only fully understand how skin cells change with ageing but also to test drug-drug interactions. In vitro ageing, models can also be used to measure levels of gene expression and cell growth rate in skin cells.

Dermal Cell Models For Toxicity Analysis

In vitro systems, such as cultivating primary human cells, are becoming more essential for making decisions in the drug development process, even though animal models are still one of the most crucial tools in preclinical toxicity investigations. Traditionally, in vitro models were created using epithelial cells like HeLa, CHO, fibroblasts and immortalized cell lines. Although these cell lines are relatively simple to culture than primary cells, they have an infinite lifespan that can cause mutations, and the majority of them come from cancer tissues.

The strategy also aids in understanding variations and differences in performance characteristics as studies switch from an in vitro human model to in vivo animal investigations. Many of the ethical considerations about using animals that have been raised around the world are also reduced by this method. In vitro skin models often focus on analysing the release of the important inflammatory cytokines that initiate tissue repair while also assessing cell viability as the primary goal. Since it more accurately enables the restoration of human skin tissue, 3D culture is considered a more equivalent format to humans in vivo, according to growing scientific evidence. 

Types of skin cell toxicity tests used to evaluate the suitability of substrates: 

  • Skin Irritation Test: Various chemical exposure dosages are used in skin irritation/corrosion testing to determine if skin damage is reversible or irreversible.
  • Skin Sensitization: Testing for skin sensitization results in contact dermatitis after introduction to a chemical agent.
  • Dermal Penetration: The degree and speed at which a chemical penetrates the body through the skin are known as dermal penetration.
  • Acute Systematic Toxicity: Adverse effects that manifest quickly after receiving a single (often very large dosage) of a chemical via dermal absorption is referred to as acute systemic toxicity.

Looking ahead

As research advances, more attention will be paid to both basic research and models that enable the screening of pharmaceutical substances in vitro,  models that imitate the complicated skin system in repeatable models of ageing. High-throughput screening and 3D cell culture are required for skin research methods. Creating models that permit this research could benefit not only the cosmetics sector but also researchers looking into skin problems and those testing treatments on our largest organ. In vitro skin models often focus on analysing the release of the important inflammatory mediators that initiate tissue repair while also assessing cell viability as the primary endpoint. Three-dimensional (3D) culture is a more relevant format to humans in vivo because it more nearly permits the regeneration of human skin tissue, according to growing scientific evidence. 

Although skin ageing is primarily aesthetic, it has an impact on many physiological functions and disorders throughout the body. It turns out that skin ageing goes deeper than that.