Zombie cells, also known as senescent cells, are cells that have stopped dividing and are no longer able to perform their normal functions. These cells accumulate in the skin with age and contribute to the aging process. To help the skin gets rid of these undesired cells, Clariant Actives & Natural Origins and its partner Biospectrum developed Celyscence, a natural active ingredient that demonstrated a strong efficacy in the reduction of the number of senescent cells in the skin, thanks to a triple mode of action: senescence prevention, senolytic effect and senomorphic effect.

Zombie cells: when aged cells refuse to die

In the normal life cycle of a cell, after several division cycles the cell becomes less functional, meaning its biological processes are impaired. Its division speed slows down, and its ability to produce components useful for the tissues is decreased. These aged cells are normally eliminated through the apoptosis process and replaced by new, fully functional cells. But as we age, some of them are not correctly eliminated. They remain in a “dead-alive” state and are called senescent cells, or also “zombie cells”.

Not only do they no longer proliferate but they also have a strong resistance to apoptosis. As they refuse to die, they are not eliminated as would happen normally. They are also too damaged to carry out their normal functions and showcase a low metabolic activity, resulting for instance in lower production of collagen, a protein fundamental for tissue regeneration. At the same time, they interfere with their environment through the release of SASP molecules (senescence-associated secretory phenotype factors), like inflammation-causing cytokines and metalloproteinases that can harm nearby healthy cells. Helping skin to clear out these zombie cells should support its regeneration and delay its aging.

Celyscence: helps the skin eliminates zombie cells for a rejuvenating effect

An innovative replicative senescence model

A replicative senescence model using primary human dermal fibroblasts was developed to mimic the physiological senescence process that occurs in skin. The profiles of non-senescent cells, which had undergone less than 8 passages in culture, were compared to those of senescent cells obtained after at least 40 passages. The higher the number of passages, the more pronounced the state of senescence.

The number of cells expressing SA-β-galactosidase, a well-known marker indicating high cellular senescence, was drastically increased in the senescent fraction. So as two senescence markers: γH2AX, which indicates DNA damage that activates growth arrest; and p21, the primary mediator of the downstream pathway for cell cycle arrest. Moreover, the expression of key SASPs, i.e. IL-6, IL-8 and MMP-1, known to be more elevated in senescent cells, were highly stimulated in the senescent fibroblast model, attesting to the senescent state of the cells.

This replicative senescence model was used to study the potential of Celyscence in depth.

Senolytic effect: eliminating senescent cells

This replicative senescence model was used to evaluate the capacity of Celyscence to trigger apoptosis. The active ingredient at 1% and 2% was applied on non-senescent and senescent cells. After three days of treatment, the number of apoptotic cells was only affected in the senescent model, without touching the healthy cells. This demonstrates that Celyscence specifically induced apoptosis of senescent cells, encouraging these cells to self-destroy which in turn limits their negative effects on their surrounding environment.

Senomorphic effect: reprogramming senescent cells

The senomorphic activity was demonstrated through the inhibition of SASPs. Two pro-inflammatory cytokines, IL-6 and IL-8, and the major metalloproteinase MMP-1, whose main substrate is collagen I, were investigated. Celyscence drastically reduced all these SASPs’ secretions, mitigating their side effects. Moreover, thanks to the decrease of the two senescence markers p21 and γH2AX, the senescent cells were reverted into cells with a young profile. Ultimately, the senescent cells were able to re-synthetize collagen type I when treated with Celyscence.

On one hand, senescent cells are eliminated and on the other hand, cells are rejuvenated to reverse their detrimental phenotype, improving their metabolism and function.

Celyscence promotes healthy aging by improving skin’s hydration, brightness and firmness

Thirty women aged between 50 and 60 years old, presenting visible wrinkles on the neck and decolletage, were enrolled. For 56 days, one half of the panel applied a product containing 3% Celyscence on the neck and chest, and the other half a placebo product. Clinical measurements were done after 14, 28 and 56 days. In addition, twice daily for 14 days, all participants also applied either a cream containing 3% Celyscence or a placebo cream on one half of the face to enable specific face observation.

The skin on the decolletage is one of the most neglected parts of the body and particularly susceptible to dryness and decrease in skin brightness due to cellular senescence. Thanks to Celyscence, decolletage brightness was improved by 3.2% after 56 days, revealing a more luminous and radiant complexion. Hydration increased by 8.6% after 14 days and by 14% after 56 days.

Moreover, melanin content on the face decreased by more than 5% after 2 weeks, counteracting the deleterious effects of senescent cells on dull and uneven complexion.

Overall, Celyscence restores the crucial ability of fibroblasts to produce collagen, ensuring aged tissue repair, for visible firming results on the neck and decolletage.

By targeting senescent cells, Celyscence naturally helps women feel more confident in their own beauty as they age!

Technical information

• Preservatives: none
• China: IECIC-listed
• COSMOS approved
• Naturality (ISO 16128): 100% natural origin content
• Recommended use: 1-5%
• Appearance: yellow to slightly brown liquid
• Solubility: water-soluble
• INCI: Glycerin, Water, Silybum Marianum Extract