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Autophagy activators stimulate the removal of advanced glycation end products in human keratinocytes

T Laughlin¹, Y Tan^2,3,4, B Jarrold¹

¹The Procter & Gamble Company, Mason Business Center, Mason, OH, USA.

Journal of the European Academy of Dermatology and Venereology : JEADV

|June 20, 2020

Abstract

Background:

The accumulation of advanced glycation end products (AGEs) can impact cellular homoeostasis and protein structure, thus is implicated in numerous skin conditions including yellow, dull appearance. AGE formation is irreversible; thus, understanding of the recycling process of AGEs in the skin is critical for addressing skin appearance conditions.

Objective:

To determine whether (i) accumulation of AGEs occurs in dull appearance group among young population (age 20-29) (ii) in vitro autophagy stimulation results in reduction of AGEs in keratinocytes.

Methods:

Facial cheek biopsies were collected from Chinese women (age 20-50) exhibiting either dull or non-dull appearing skin. Histological assessment of glycation was performed for representative subjects among the 20-29 years sub-group by immunofluorescence staining of AGEs. LC-MS methods and keratinocyte cell culture were used to assess impact of autophagy modulators and skin care materials on carboxymethyl lysine (CML) amount, a representative AGE.

Results:

Notable amounts of AGEs were observed in the epidermal samples among young females. Interestingly, the amount of AGEs was significantly higher among the dull skin appearance group. Treatment of keratinocytes with glyceraldehyde (GLA) enhanced CML in the cells, and postglycation treatment with autophagy activators reduced CML. Two skin care materials, Nymphaea alba flower extract (a.k.a. white water lily extract) and sucrose dilaurate, were identified based from in vitro autophagy activation and found to reduce CML in keratinocytes.

Conclusion:

We found AGEs accumulate in the facial epidermis even among young people, correlating to a yellow and dull appearance. We also demonstrated in vitro activation of autophagy can reduce AGEs in keratinocytes, and autophagy activating skin care materials, N. alba flower extract and sucrose dilaurate, also reduce AGEs in the keratinocyte in vitro model. These data suggest epidermal AGEs contribute to the dull skin appearance, and autophagy activators may provide an effective solution to improve dull appearance by removing and recycling the accumulated glycation in the skin.

Insights

Advanced glycation end products (AGEs) accumulate in young skin, causing dullness. Activating autophagy, a cellular recycling process, effectively reduces AGEs and can improve skin appearance.

Area of Science:

Dermatology
Biochemistry
Cell Biology

Background:

Accumulation of advanced glycation end products (AGEs) impacts skin homeostasis and protein structure, contributing to conditions like dull and yellow skin appearance.
Understanding AGEs recycling is crucial for managing skin appearance issues, as AGE formation is irreversible.

Purpose of the Study:

To investigate AGEs accumulation in young individuals with dull skin.
To determine if in vitro autophagy stimulation reduces AGEs in keratinocytes.

Main Methods:

Facial cheek biopsies from women (20-50 years) with dull/non-dull skin were analyzed for AGEs using immunofluorescence.
Keratinocyte cell cultures were used to assess the impact of autophagy modulators and skincare ingredients on carboxymethyl lysine (CML) levels via LC-MS.

Main Results:

Significant AGEs accumulation was observed in the epidermis of young females, particularly in those with dull skin.
Glyceraldehyde (GLA) increased CML in keratinocytes, while autophagy activators reduced CML.
Nymphaea alba flower extract and sucrose dilaurate demonstrated in vitro autophagy activation and reduced CML in keratinocytes.

Conclusions:

Epidermal AGEs accumulate even in young individuals, correlating with dull skin appearance.
In vitro autophagy activation reduces AGEs in keratinocytes.
Autophagy-activating skincare ingredients, Nymphaea alba flower extract and sucrose dilaurate, show potential for improving dull skin by reducing AGEs.

Read full analysis

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