DIAGNOSTIC METHOD OF A SKIN SHOWING SIGNS OF AGING

Abstract

This invention related to a method for diagnosing a skin displaying signs of aging, based on measuring the level of expression of the gene encoding the IDE. The present invention also relates to a method for the cosmetic treatment of skin. This invention also relates to a method for identifying a compound for reducing the signs of the aging of the skin as well as a kit.

Claims

1. A diagnostic method of a skin having signs of aging, in a subject, said method comprising the following steps: a) measuring the level of expression of the gene encoding the insulin-degrading enzyme (IDE), in a skin sample of said subject.

2. A method of cosmetic treatment of a skin having signs of aging in a subject, said method comprising the following steps: a) measuring the level of expression of the gene encoding the IDE, in a skin sample of said subject; b) deducing from the step a) if the skin of said subject has signs of aging; c) if the skin is identified as having signs of aging in the step b), treating said skin with a cosmetic composition allowing for the reduction and/or the slowing down of the progression of the signs of aging of the skin.

3. A method of identifying a compound suitable for reducing and/or slowing the progression of the signs of aging of a skin, said method comprising the following steps: a) measuring the level of expression of the gene encoding the IDE, in a skin sample exposed to said candidate compound; b) comparing said level of expression measured in step a) to the level of expression of the gene encoding IDE in a skin sample not exposed to said compound; c) identifying said candidate compound as a compound suitable for reducing and/or slowing the progression of the signs of aging of a skin when an increase in the level of expression of the gene encoding IDE in the skin sample exposed to said candidate compound is detected, with respect to the level of expression of the gene encoding IDE in the skin sample not exposed to the candidate compound.

4. The method according to claim 3, wherein said skin sample is a skin cell culture, an epidermis culture, a reconstructed whole skin, a human skin explant, or a skin sample from a subject.

5. The method according to claim 1, wherein the skin sample is taken by rubbing the skin surface or using an adhesive surface.

6. The method according to claim 1, wherein the level of expression of the gene encoding IDE is determined by the level of expression of mRNA of said gene or by measuring the level of expression of the protein encoded by said gene.

7. The method according to claim 6, wherein the level of expression of the protein encoded by the gene encoding IDE is measured using at least one specific ligand of IDE protein.

8. A kit comprising: a) a means for measuring, in a skin sample, the level of expression of the gene encoding IDE, b) an instruction leaflet, c) a means for taking the skin sample and d) a standard range for the expression of the gene encoding IDE.

9. The kit according to claim 8, wherein the means for measuring, in a skin sample, of the level of expression of the gene encoding IDE is a specific ligand of IDE or a complementary nucleotide sequence of the mRNA or a fragment of the latter, a pair of primers or a specific probe of the mRNA of the IDE.

10. A method for the identifying of a compound suitable for reducing and/or slowing the progression of the signs of aging of a skin, which comprises using a kit according to claim 8.

11. The method according to claim 2, wherein the skin sample is taken by rubbing the skin surface or using an adhesive surface.

12. The method according to claim 3, wherein the skin sample is taken by rubbing the skin surface or using an adhesive surface.

13. The method according to claim 4, wherein the skin sample is taken by rubbing the skin surface or using an adhesive surface.

14. The method according to claim 2, wherein the level of expression of the gene encoding IDE is determined by the level of expression of mRNA of said gene or by measuring the level of expression of the protein encoded by said gene.

15. The method according to claim 3, wherein the level of expression of the gene encoding IDE is determined by the level of expression of mRNA of said gene or by measuring the level of expression of the protein encoded by said gene.

16. The method according to claim 4, wherein the level of expression of the gene encoding IDE is determined by the level of expression of mRNA of said gene or by measuring the level of expression of the protein encoded by said gene.

17. The method according to claim 5, wherein the level of expression of the gene encoding IDE is determined by the level of expression of mRNA of said gene or by measuring the level of expression of the protein encoded by said gene.

18. The method according to claim 14, wherein the level of expression of the protein encoded by the gene encoding IDE is measured using at least one specific ligand of IDE protein.

19. The method according to claim 15, wherein the level of expression of the protein encoded by the gene encoding IDE is measured using at least one specific ligand of IDE protein.

20. The method according to claim 16, wherein the level of expression of the protein encoded by the gene encoding IDE is measured using at least one specific ligand of IDE protein.

Description

EXAMPLE

[0047] Wrinkles of the crow's feet, wrinkles under the eyes and elastosis were evaluated on the eyes and the entire face of 376 women aged 36 to 75 years. The level of protein expression of the gene encoding IDE was also evaluated on these women's cheeks, by means of a D-squame sample wherein the soluble protein extract was analyzed using an ELISA test conducted on a chip.

[0048] After having discretised the signs of aging, the statistical analysis of the results obtained shows a correlation between the presence of these signs of aging and the level of expression of IDE.

TABLE-US-00001 TABLE 1 clinical signs P Threshold of aging values (ng/ml) AUC* Sensitivity Specificity Wrinkles of the <0.001 11.0 64.36% 66.49% 57.74% crow's feet Wrinkles under <0.001 11.0 61.25% 63.08% 54.66% the eyes Elastosis <0.001 11.0 60.21% 63.95% 54.89% *AUC: area under the curve

[0049] The statistical analysis demonstrates an association between the concentrations in IDE and the following signs of aging: 1wrinkles of the crow's feet, 2wrinkles under the eye and 3elastosis, with p values <0.001 (coming from logistic regression models). A decrease in the level of expression of the gene encoding IDE is therefore characteristic of the appearance of signs of aging and in particular of elastosis, the appearance of wrinkles of the crow's feet and the appearance of wrinkles under the eyes. The analysis of the results moreover made it possible to define thresholds between 9.35 and 12.65 ng/ml which could therefore be used as reference values.

[0050] Several statistical methods were used to evaluate the performance of the univariate models of predictions of these clinical signs with the IDE concentrations, in particular by the determining of the AUC.