Shiseido Discovers New Mechanism Accelerating the Aging of Skin
-Development of Anti-Aging Ingredients to Control Negative Effects of Serpin b3 -

Shiseido has discovered that an increase in the rogue protein, serpin b3, causes an accumulation of damage in the
epidermis, and even negatively affects the basement membrane and dermis. It has been determined that the aging
of skin is accelerated by the repeated occurrence of this kind of damage (figure 1). It has also been discovered that the continuous use of the amino acid derivative, 1-piperidine propionic acid, in high concentrations is extremely effective in controlling the aging of skin (figure 2).
Shiseido will apply the results of this research to the development of skincare products “to nurture smooth, youthful skin with firmness and elasticity.”

Research and Knowledge to Date on Serpin b3

The skin plays an extremely important role as a barrier protecting our bodies from the outside environment.
Healthy skin forms this barrier through a highly elaborate mechanism to maintain beautiful, resilient skin. When
this mechanism breaks down, the surface of the skin enters into a premature state known as “parakeratosis
(abnormal keratinization),” resulting in a profound deterioration of its ability to act as a barrier. This phenomenon
has been known since the early days, but the causative factor of “parakeratosis” remained a mystery for a long
time.
Shiseido continued its challenge to ascertain the cause of this phenomenon, and finally succeeded in clarifying it
to be serpin b3, which was announced at the 24th IFSCC(1) Conference (2006). The results of this research won the Honorary Mention Award for Basic Research at the conference, and was highly appraised in Japan and
internationally. Furthermore, the research focused on components within the living body to develop ingredients to
control the production of serpin b3, and found 1-peperidine propionic acid (1PP), the amino acid derivative, to be
effective.

1 The International Federation of Societies of Cosmetic Chemists. Formed in 1959 with the participation of the Societies of Cosmetic Chemists of eight countries. It is currently an organization boasting approximately 15,000 members from 47 countries. The conferences are held biannually on years of even numbers.

New Knowledge on Serpin b3

Shiseido has not grown complacent with the results obtained so far, and has continued to carry out further
research. As a result, the company has made further discoveries that (1) serpin b3 is a factor related to skin aging, (2) an increase in serpin b3 not only damages the surface and stratum corneum of the skin, but also propagates and amplifies the damage to the whole epidermis, and furthermore (3) it propagates damage to the basement membrane and dermis, and accelerates skin aging.
To begin with, it was determined that an increase in serpin b3 in the epidermis obstructs the self-defense system(2) which prompts cells to eliminate themselves when they accumulate irreparable damage. Epidermal cells with
accumulated damage that have not been eliminated, produce and release various damage-inducing factors which
trigger a variety of aging damage. The level of serpin b3 rises in epidermal cells in the vicinity exposed to these
damage-inducing factors, and it has been ascertained that this triggers the release of yet more damage-inducing
factors, leading to a vicious circle of damage propagation.
The damage-inducing factors released by epidermal cells with raised levels of the serpin b3 have also been found
to weaken the function of the dermis and basement membrane. The research showed that an increase in serpin 3
has negative effects on the whole skin, and it was discovered to be a new mechanism in the acceleration of skin
aging.

2 A cell removal system called apoptosis (programmed cell death) found in the tissue of living organisms.

Development of Active Ingredient to Control Skin Aging

As the result of research to nurture smooth, youthful skin with firmness and elasticity by controlling the production of serpin b3, which is the cause of accelerated aging, a serpin b3 inhibiting ingredient 1PP was formulated in high concentrations and was found to be most effective.
1PP is particularly effective in inhibiting the production of serpin b3 which accelerates aging, and it is also an extremely effective ingredient in rejuvenating damaged skin. It is expected to be used in anti-aging skincare products in the future.