PERSONAL CARE

Vincience Biofunctionals

Chronogen

Description
Innovative anti-aging tetrapeptide, designed using advanced
molecular biology and inspired by epigenetic science, to boost
the expression of clock genes
The circadian rhythm is an important regulatory function that skin cells
need to regenerate and revitalize for a fresher appearance. This internal
clock serves to optimize repair activities around the day-night cycle
of the earths rotation and is synchronized with other cells and organs
operating under the same schedule.
For many years, time-keeping functions were thought to be exclusively
centralized in the brain within the suprachiasmatic nucleus. Although
this master clock plays an important role, recent research has shown
that cells can independently tell time through a very precise molecular
mechanism involving the expression and regulation of circadian genes
(Clock, Per1, Bmal1, Tim and Cry).
These clock genes give tempo to cells, orchestrating and regulating
more than 20% of gene expressions. Factors such as UV radiation (even
in low doses) can decrease the expression of these clock genes and
desynchronize the cells circadian rhythm.

Benefits

Enhances expression of CLOCK, BMAL1 and PER1, in-vitro and ex-vivo

Helps preserve skin from UV damage during the day
In-vitro, helps better DNA repair

The bio-engineered peptide contained in Chronogen has been

designed to improve the expression of the proteins involved in the
clock mechanism and represents a major breakthrough strategy in
cosmetic science.

Cosmetic Applications

Because consumers often apply cosmetic products around a day-night

regimen, the use of formulations aiming the circadian rhythms may help
further optimize cellular protection and renewal. In-vitro results show
that Chronogen specifically boosts cellular natural defenses against UV
damage (important during the day) and helps better natural DNA
repair (important at night).

Day time formulations to help boost skins natural defenses against UV

Night time formulations to boost the skins repair process

Innovative anti-aging formulations based on epigenetic science

Formulations to help optimize the protective and regenerative
cycle of skin

Introduction

For many years, the consensus was that time-keeping functions were highly centralized in a master clock located in the
suprachiasmatic nucleus within the brain.
More recently, discoveries have shown that each cell exhibits a deeply embedded self-sustained circadian rhythm used to
govern gene expression.
This mechanism has become a major focus in biology and medical research. With Chronogen, ISP is introducing to the personal
care market an advanced technology, inspired by epigenetic science, designed to help consumers optimize skin regeneration and
the natural defenses against UV damage.

Circadian Regulators: A Cellular Metronome

The skin cells defense and repair is orchestrated by each cells own internal clocks. Preserving optimal expression of these clock
genes is a challenge because even low UV exposure can knockdown these regulating clock genes for more than 24 hours.
The time-keeping mechanism is modeled as a network of transcriptional and post-translational feedback loops synchronized on
the day-night cycles. It involves several genes including Clock, Per1, Bmal1, Tim and Cry. They help to regulate the cycle in which
cells turn on and off repair functions, ensuring to coordinate these functions with UV exposure. Hence, targeting clock genes
represents a major breakthrough in anti-aging strategy in cosmetic science.

CLOCK

PER1

+ 41%

+ 52%

Control

Chronogen (1%)

Quantification

Cell Culture: Human skin biopsy Product Application: Chronogen (1%), twice a day Application Time: 62 hours
Evaluation: Immunofluorescence staining in green of circadian proteins (CLOCK or PER1) Quantification: Image analysis

In-vitro and ex-vivo tests suggest that Chronogen can boost the expression of circadian gene proteins: CLOCK, BMAL1 and PER1.
Chronogen provides an innovative anti-aging breakthrough strategy by aiming for optimal expression of the internal clock
gene proteins.

DNA Repair and Protection

DNA is constantly submitted to damaging stresses (UV rays and free radicals). In particular, when UV exposure is the highest
during the day, DNA strands must be configured in a way to ensure maximum protection. During the night, when exposure is
minimal, cells undertake DNA repair. To ensure cycle optimization, the genes regulating the circadian rhythm need protection
from external damage caused by UV exposure.
Day protection
Control

Chronogen (1%)

(before UV irradiation)

UVB
(60 mJ.cm-2)

Cell Culture: Fibroblasts

Product Application: Chronogen (1%) once a day
Protocol:
- Application of Chronogen (1%) for 24 hours
- UVB (60 mJ.cm-2)
- Evaluation of DNA damage by comet assay
1 hour after UV irradiation

The average measure of the tail moment length, representative of the amount of DNA damage, was 78% less when Chronogen
was applied to the cells prior to exposure compared to the control. In-vitro results suggest that Chronogen can help boost the
natural DNA protection from UV radiation.
Night repair
Control

UVB
(60 mJ.cm-2)

Chronogen (1%)

(after UV irradiation)

Cell Culture: Fibroblasts

Product Application: Chronogen (1%) once a day
Protocol:
- UVB (60 mJ.cm-2)
- Application of Chronogen (1%) for 24 hours
- Evaluation of DNA damage by comet assay

The average measure of the tail moment length, representative of the amount of DNA damage, was 81% less when Chronogen was
applied to the cells for 24 hours after exposure compared to the control. In-vitro results suggest that Chronogen can help cells better
repair DNA from UV damage.

In-vivo Skin Protection and Regeneration

Two double-blind studies were completed. Each was carried out over 17 days on 12 volunteers (age 24-37) using a cosmetic
formulation containing Chronogen (1%) vs. a placebo. A standard quantity of each (2 mg.cm-2) was applied on the thighs twice a
day, in the morning and evening.
For the first study, the treated areas were exposed to full solar spectrum irradiation (2 MED) on day 15. Twenty four hours later (day
16) an observation was made using confocal microscopy (Vivascope), with the number of sunburn cells (SBC) counted. The areas
treated with the Chronogen formulation had 38% fewer SBCs compared to the areas treated with the placebo, confirming the
previously observed in-vitro and ex-vivo results which suggest that Chronogen may help boost the skins natural defenses against
UV irradiation.
In the second study, the stratum corneum renewal was measured using a dihydroxyacetone (DHA) method that stains proteins.
Here, DHA was applied on two symmetric zones of the thighs at day 0, and photos and grading were recorded at days 1, 4, 7, 11,
14 and 16. For 11 out of the 12 volunteers, the area treated with the Chronogen formulation was observed to have a faster fading
of the DHA staining compared to the placebo treated area, with the best effects noted at day 4 (75% of the volunteers) and day 7
(67% of volunteers). Since skin turnover is directly proportional to the disappearance of the skin color (brown/orange) caused by
the application of DHA, the results suggest that Chronogen may help to boost skin turnover and regeneration.

Specifications
Form:
Color:
Odor:
Solubility:
Preservative:

Limpid solution
Colorless
Characteristic
Water soluble
Phenoxyethanol, Sodium Benzoate

INCI Name

Water (Aqua), Butylene Glycol, Tetrapeptide-26

Formulation Guidelines

Add in water phase below 40C; in emulsion add on

cool-down post-emulsion
Recommended use levels: 1% (clinically tested at 1%)
The above formulation information is for guideline purposes only. Some
products may be formulated outside of the parameters of these guidelines.
Please contact ISP for more information.

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Trademark registration applied for Registered trademark of the ISP group International Specialty Products. 2010 Printed in USA.
The information contained in this brochure and the various products described are intended for use only by persons having technical skill and at their own discretion and risk after
they have performed necessary technical investigations, tests and evaluations of the products and their uses. This material is for informational purposes only and describes the
scientific support for the use of Chronogen as an ingredient in cosmetic products intended to enhance appearance and other cosmetic benefits. While the information herein is
believed to be reliable, we do not guarantee its accuracy and a purchaser must make its own determination of a products suitability for purchasers use, for the protection of the
environment, and for the health and safety of its employees and the purchasers of its products. Neither ISP nor its affiliates shall be responsible for the use of this information, or
of any product, method, formulation, or apparatus described in this brochure. Nothing herein waives any of ISPs or its affiliates conditions of sale, and WE MAKE NO WARRANTY,
EXPRESS OR IMPLIED, OF MERCHANTABILITY OR FITNESS OF ANY PRODUCT FOR A PARTICULAR USE OR PURPOSE. We also make no warranty against infringement of any patents
by reason of purchasers use of any information, product, method or apparatus described in this brochure.

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