This invention relates to the use of an activator of skin-cell autophagy for improving cellular and tissue longevity of the skin. The object of the invention is also specifically a cosmetic skin treatment process for promoting cellular and tissue longevity of the skin, comprising the application on the skin of an activator of skin-cell autophagy.
Aging is a complex process that depends on genetic determinism, epigenetic mechanisms, and various external influences, such as the sun, atmospheric pollution, food, lifestyle, etc. The longevity and the decline of cells and tissues of the skin are therefore under the influence of numerous factors.
To effectively prevent the aging of the skin, including premature aging, and to limit the appearance of negative effects that result therefrom, it is important to delay the appearance of the phenomena of cellular senescence and to limit tissue degeneration.
This is why the objective of this invention is to find a cosmetic solution that is capable of acting on molecular mechanisms that are strongly involved in cellular and tissue longevity and thus to limit and to push back the appearance of the signs of aging of the skin.
To respond to this, this invention proposes using an activator of skin-cell autophagy.
Actually, surprisingly enough, the application on the skin of an activator of skin-cell autophagy makes it possible to increase cellular and tissue longevity of the skin.
The object of the invention is therefore the use in a cosmetic composition of at least one activator of skin-cell autophagy as an active ingredient intended to increase cellular and tissue longevity of the skin.
According to the invention, the use of an activator of the autophagy makes it possible to delay the appearance of the phenomena of cellular senescence of the skin and to limit the tissue degeneration by acting on molecular mechanisms that are strongly involved in cellular and tissue longevity. It makes it possible to preserve the functionality of the tissues of the skin and the appearance of the signs of aging in the area of the skin.
According to a particular aspect, the object of the invention is specifically a cosmetic skin treatment process for increasing cellular and tissue longevity, comprising the topical application on the skin of an active ingredient that activates skin-cell autophagy.
This invention is now described in detail.
Autophagy is a mechanism for recycling and detoxifying cellular components and organelles. Autophagy makes it possible in particular to regulate, repair and eliminate the proteins of long service life in the cells, thus ensuring a control during the differentiation and aging of the human skin.
On the cellular plane, the autophagy mechanism comprises four stages: the initiation, the formation of an initial vacuole, called an autophagosome, which sequesters the cytoplasmic material, the maturation of the autophagosome in a degradative vacuole, and the fusion with the lysosome, until the sequestered material is degraded.
Activator or stimulator of autophagy in terms of the invention is defined as a molecule or an active ingredient, or a mixture of molecules or active ingredients, capable of activating the mechanism of the autophagy.
The object of this invention is therefore an activator of skin-cell autophagy for its application as an active ingredient in a composition with topical application on the skin, with said active ingredient and/or said composition being intended to increase cellular and tissue longevity of the skin.
In particular, the object of the invention is the use of an active ingredient that activates skin-cell autophagy as an active ingredient in a composition with topical application, with said active ingredient and/or said composition being intended to act on the molecular mechanisms involved in cellular and tissue longevity of the skin, in particular:
Lipofuscin, also called “age pigment,” is a non-degradable, autofluorescent compound that gradually accumulates during repeated stress or with age and that impedes proper operation of the cell. In the area of cutaneous tissue, the deposits of lipofuscin contribute to the appearance of age spots that frequently characterize skin that is aged or over-exposed to the sun. Its accumulation is associated with a reduction of cellular longevity.
According to the invention, however, the use on the skin of an activator of skin-cell autophagy makes it possible to limit the accumulation of lipofuscin in the skin cells and consequently to increase cellular and tissue longevity of the skin.
Furthermore, the synthesis of MMP-1, matrix metalloproteinase responsible for the degradation of collagen I and III fibers, is increased in the skin cells during the aging of the skin. This degradation of the three-dimensional matrix network of the skin cells is reflected on the surface of the skin by a release, a loss of firmness, and the appearance of wrinkles.
According to the invention, however, the use on the skin of an activator of skin-cell autophagy makes it possible to inhibit or to limit the synthesis of MMP-1 in the skin cells and consequently to reduce the degradation of the extracellular matrix and therefore to increase cellular and tissue longevity of the skin.
These actions are reflected visually by a reduction of the signs of aging of the skin, in particular a reduction of wrinkles and an improvement of the homogeneity of the complexion.
Preferably, the stimulator of the autophagic activity of the skin cells that is useful according to the invention is a synthetic molecule or an active ingredient that is obtained from at least one plant, one alga or one yeast.
The activator of autophagy can be, for example, an active ingredient that is capable of activating skin-cell autophagy, obtained from Prunus cerasus or Metschnikowia hawaiiensis.
According to one aspect of the invention, the activator of skin-cell autophagy is able to be selected by a test that is carried out on skin-cell cultures as described in the patent FR-2,939,316. The activator of autophagy is therefore able to be selected by a test that is carried out on skin-cell cultures comprising the following stages:
The activators of autophagy for use according to the invention can be incorporated in cosmetic compositions in various galenical forms, adapted to administration by cutaneous topical means.
These compositions can come in particular in the form of creams, oil-in-water emulsions, water-in-oil emulsions, multiple emulsions, solutions, suspensions or powders. They can be more or less fluid and have the appearance of a cream, a lotion, a milk, a serum, an ointment, a gel, a paste, or a foam, or in solid form.
These compositions contain between 0.01 and 15% by weight of activators of skin-cell autophagy according to this invention, preferably between 0.5% and 4%.
According to another aspect, the object of the invention is also a cosmetic skin treatment process for increasing cellular and tissue longevity, comprising the topical application on the skin of an activator of skin-cell autophagy or a composition that contains an activator of skin-cell autophagy. In particular, the object of the invention is a cosmetic process for treatment of photoexposed skin to delay the appearance of aging, comprising the topical application on the skin of an activator of skin-cell autophagy or a composition that contains an activator of skin-cell autophagy.
To illustrate the invention, multiple activators of autophagy have been selected and tested for studying their capacity for increasing cellular and tissue longevity of the skin.
One example of an activator of autophagy that is useful according to the invention is an active ingredient that is obtained from the fruit-bearing peduncle of Prunus cesarus that responds positively to the test carried out on skin-cell cultures as described in the patent FR-2,939,316.
Such an active ingredient can be obtained by implementing the following stages:
The active ingredient contains approximately 40% of oligosaccharides of a size of between 180 Da and 1,300 Da.
Another example of a useful activator of autophagy according to the invention is an active ingredient that is obtained from Metschnikowia hawaiiensis that responds positively to the test carried out on skin-cell cultures as described in the patent FR-2,939,316.
Such an active ingredient can be obtained by implementing the following stages:
The active ingredient contains approximately 50% of peptides of a size of between 243 Da and 5,000 Da.
The objective of this study is to evaluate the effect of active ingredients on the production of lysosomes, organelles involved in the autophagic mechanism of the cell.
This study was carried out by flow cytometry on normal human fibroblasts subjected to moderate and repeated treatments with hydrogen peroxide (H2O2) making it possible to induce cellular senescence.
The operating procedure is described below.
On D0, the normal human fibroblasts are inoculated in the suitable medium.
For several days, the fibroblasts are treated:
A specific marking of the lysosomes is carried out by fluorescence.
The analysis of fluorescent marking is carried out by flow cytometry. The intensity of green fluorescence is proportional to the quantity of lysosomes. The greater the fluorescent intensity, the greater the formation of lysosomes.
The results are presented in the table below:
hawaiiensis Extract
Tested at 1% on stressed human fibroblasts, the active ingredients extracted from the cherry tree and extracted from Metschnikowia hawaiiensis significantly boost the production of lysosomes by 45% and 99% in comparison to the control stressed fibroblasts.
By increasing the production of lysosomes in the cell cultures, these active ingredients activate the autophagy mechanism.
This composition is an emulsified gel, with pH 5.
It is obtained by implementing the following stages:
This composition is emulsified gel, with pH 5.3.
It is obtained by implementing the following stages:
This composition comes in the form of a serum with a pH of 6.2.
It is obtained by implementing the following stages:
1. 1. Study of the Accumulation of Lipofuscin Aggregates
The objective of this study is to evaluate the capacity of activators of autophagy to limit the formation of lipofuscin aggregates that alter cellular function and that are correlated with the reduction of cellular longevity.
This study was carried out by confocal microscopy on normal human fibroblasts subjected to moderate and repeated treatments with hydrogen peroxide (H2O2), making it possible to induce cellular senescence.
The operating procedure is described below.
On D0, the normal human fibroblasts are inoculated in a culture medium. The cells are then incubated at 37° C.
For several days, the fibroblasts are treated and stressed:
The visualization of the lipofuscin is carried out using a microscope coupled to image analysis software. Lipofuscin manifests itself through the appearance of autofluorescent grains in the cell cytoplasm. The quantity of lipofuscin is proportional to the intensity of autofluorescence of the cells.
The results that are obtained are expressed in terms of fluorescence intensity/number of cells (UA) and are presented in the table below:
The cytoplasmic accumulation of lipofuscin aggregates is significantly increased when the normal human fibroblasts are subjected to a moderate and repeated H2O2 stress. In addition, it is noted that the activators of autophagy make it possible to reduce the accumulation of lipofuscin in comparison to control stressed fibroblasts.
1. 2. Study of the Protection of the Extracellular Matrix
The objective of this study is to evaluate the effect of activators of skin-cell autophagy on the synthesis of MMP-1, of which the synthesis is increased during aging.
The study was carried out by ELISA metering on normal human fibroblasts having undergone moderate and repeated treatments with hydrogen peroxide (H2O2), making it possible to induce cellular senescence.
The operating procedure is described below.
On D0, the normal human fibroblasts are inoculated in a culture medium. The cells are then incubated at 37° C.
For several days, the fibroblasts are treated and stressed:
The cellular supernatants are recovered. The MMP-1 metering is carried out using an ELISA metering kit.
The results that are obtained are presented in the table below:
The synthesis of MMP-1 is significantly increased when the normal human fibroblasts are subjected to a moderate and repeated H2O2 stress.
In addition, it is noted that the activators of autophagy make it possible to reduce by 35% the synthesis of MMP-1 in comparison to the control stressed fibroblasts. This effect is significant and dose-dependent. The integrity of the matrix environment is thus preserved.
2. 1. Study of the Anti-Wrinkle Effect on Photoexposed Skin
With age, the aging of tissue is reflected in the cutaneous area by the appearance of wrinkles and age spots.
The objective of this study is to evaluate, in vivo, the anti-wrinkle effect on photo-aged skin of an activator of skin cells (Example I. 1) formulated at 3% vs. placebo in the area of the crow's-feet and by fringe spraying.
The study was conducted on 20 healthy volunteers aged between 52 and 70 years and selected as having photoexposed skin.
The most relevant parameters adopted for this study are:
A reduction of these different parameters is characteristic of an improvement of the relief of the surface being studied and a reduction of wrinkles
The results that are obtained are presented in the table below:
Under the conditions of this study, after 28 days of twice-daily applications and in comparison to the placebo, the active ingredient of Example I. 1 formulated with 3% in emulsion:
This study therefore clearly shows that an activator of autophagy makes it possible to slow down the cutaneous aging and that it therefore increases the cellular longevity of the skin.
Number | Date | Country | Kind |
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13 532 98 | Apr 2013 | FR | national |
Filing Document | Filing Date | Country | Kind |
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PCT/FR2014/050888 | 4/11/2014 | WO | 00 |