Shiseido discovers new features in Alternative autophagy through joint research with The Institute of Science Tokyo

Shiseido revealed that ”alternative autophagy”*1 works to suppress photoaging of the skin caused by ultraviolet (UV) rays through joint research with Distinguished Professor at The Institute of Science Tokyo, Dr. Shigeomi Shimizu. Among autophagic pathways known as mechanisms that break down unwanted intracellular materials and restructure cells, alternative autophagy comes into play particularly when cells are damaged to a marked degree (Figure 1). In addition, Shiseido identified the Lamiaceae plant extract that activates alternative autophagy.
Alternative autophagy, a second type of autophagy discovered in 2009 by Professor Shimizu at The Institute of Science Tokyo (formerly, Tokyo Medical and Dental University), Advanced Research Initiative, Pathological Cell Biology comes into play when cells are subjected to excessive damage due to UV rays and other factors. It is distinct from regular autophagy in that it serves as a mechanism to restructure cells by destroying unwanted intracellular materials such as damaged mitochondria.*2 Alternative autophagy has been known to be involved in the maintenance of skin health, but the joint research with Shiseido led to the elucidation of its new feature, namely, the suppression of UV-induced photoaging of the skin.
Dark spots, wrinkles, and skin sagging caused by photoaging represent timeless skin problems that many people experience. Solutions developed from the findings of this joint research have enabled a revolutionary approach to prevent such skin problems from the inside of the skin, in addition to conventional approaches from the outside, such as UV protection agents and anti-inflammatory agents. The results of this research have been published in the international scientific journals Journal of Biological Chemistry (dated March 16, 2024) and Autophagy Reports (dated September 5, 2024).

*1 Another name: Golgi membrane-associated degradation = GOMED
*2 Subcellular organelles that play an important role critical to our survival, such as energy production. More than 100 mitochondria exist in one cell.

Fig1. Alternative autophagy, which comes into play when cells are subjected to excessive damage

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Research background

Shiseido started UV protection research more than 100 years ago, when photoaging of the skin had not yet widely been known. Since then, the company has been developing technologies to meet the needs of consumers whose desire is to protect the skin from the adverse effects of UV rays in all environments. In addressing the growing demand in recent years for daytime cosmetics that combine UV protection and high skin care functions, Shiseido has been pondering how such an expectation could be met. Against this backdrop, the company launched a study based on the idea that learning the specifics of relationship between UV rays and alternative autophagy, a mechanism that cells themselves have in place to maintain skin health, would be key to meeting consumer expectations.

Discovery 1: Alternative autophagy suppresses UV-induced inflammation of epidermal cells

First, it was found that when epidermal cells are exposed to ultraviolet B (UVB) radiation, mitochondria in epidermal cells become damaged. We also confirmed that, nearby UV-damaged mitochondria, the inflammasome, a group of protein complexes that command inflammation, are activated, giving rise to inflammatory factors (Figure 2-(1)). Next, it was found that, by activating alternative autophagy, the inflammatory factors can be suppressed (Figure 2-(2)). This may be due to alternative autophagy, which, when activated, results in the degradation of damaged mitochondria, thereby reducing cellular inflammatory responses.

Fig2. Alternative autophagy suppresses UV-induced inflammation of epidermal cells caused by UV rays

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Discovery 2: Collagen-degrading enzymes are produced when inflammation reaches the dermis

It was found that when alternative autophagy does not work and inflammatory factors are released outside the epidermal cells, the expression of collagen-degrading enzymes (MMPs) increases as the effects of the released inflammatory factors reach the dermal cells (Figure 3). In other words, decomposition of dermal collagen advances in the skin with a defect in the function of alternative autophagy, possibly leading to photoaging. Moreover, findings revealed that alternative autophagy may also exhibit an aging-related decline in function (Figure 4).

Fig3. Increase in collagen-degrading enzymes (MMPs) due to inflammatory factors

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Fig4. Decrease in the expression of alternative autophagy-associated factors due to aging

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Discovery 3: Alternative autophagy function is activated by the Lamiaceae plant extract

The Lamiaceae plant extract that activates alternative autophagy (Figure 5) was then identified. Due to this discovery, the active functioning of the alternative autophagy can be maintained regardless of age, and because a healthy environment inside the cell will be maintained even under exposure to UV rays, it is expected to lead to the suppression of dermal collagen degradation and photoaging of the skin.

Fig5. Alternative autophagy is activated by the Lamiaceae plant extract

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