A method for determining resistance to skin aging using gene polymorphisms
The method evaluates skin resistance to aging using SNPs from a learning model that combines genetic and environmental data, offering accurate assessments and tailored preventive measures for improved skin health.
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- SHISEIDO CO LTD
- Filing Date
- 2021-05-21
- Publication Date
- 2026-05-19
AI Technical Summary
Skin aging evaluations based on SNP analysis do not accurately reflect an individual's current skin condition due to genetic and environmental factors, leading to a sense of resignation and ineffective assessments.
A method for evaluating skin resistance to aging using SNPs selected from a learning model that integrates genetic and environmental information with skin measurement data, allowing for personalized assessments and targeted preventive measures.
Provides valid evaluations of skin resistance to aging, enabling personalized preventive measures to enhance skin health by addressing both genetic and environmental influences.
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Abstract
Description
Technical Field
[0001] The present invention relates to a method for determining resistance to skin aging, an evaluation system for resistance to skin aging, and a control program for an evaluation system for resistance to skin aging based on genetic testing. Based on the method for determining resistance to skin aging, the system, and the program of the present invention, skin counseling becomes possible.
Background Art
[0002] In recent years, skin tests based on SNP analysis of genes have been proposed, and in particular, the relationship between SNP information and skin quality has been studied for genes encoding proteins directly involved in skin quality. As a result, methods for predicting skin characteristics and skin problems have been provided based on SNP analysis results. In these studies, SNPs have been examined for genes that have been shown to be directly involved in skin quality, such as wrinkles and spots. Such target genes include, for example, MC1R, MMP1, SOD2, GPX1, ASIP, etc. On the other hand, since genes that affect skin characteristics of the skin are diverse, the relationship between SNP information and skin characteristics in more genes has also been investigated (Patent Document 1: International Publication No. 2018 / 101449).
Prior Art Documents
Patent Documents
[0003]
Patent Document 1
Summary of the Invention
Problems to be Solved by the Invention
[0004] Skin testing based on SNP analysis is performed using statistical methods that combine the subject's SNP genetic information with measurement data of their skin condition. While the skin type determined based on the subject's SNP information corresponds to the measurement data of their skin condition used in the statistical method, a problem arises in that it differs from the subject's own assessment of their skin condition. This is because skin condition changes not only due to genetic background but also due to acquired environmental factors, and the evaluation of skin type based on SNP analysis does not necessarily represent the subject's current skin condition. Furthermore, since the results of genetic testing reflect an individual's genetic background, there is a problem that subjects who undergo genetic testing may come to the conclusion that their genes cannot be changed, leading to a sense of resignation. [Means for solving the problem]
[0005] The inventors of this invention have diligently researched the aforementioned problem and have developed a method for evaluating the results of SNP analysis not from the perspective of skin resistance to aging, but from the perspective of skin resistance. The SNPs selected in this invention are those adopted in the aging model formula generated by a learning model that learns from genetic information, environmental information, and actual skin measurement data, and outputs skin constitution when genetic information and environmental information are input. Therefore, the SNPs selected in this invention are SNPs that have a large influence on the susceptibility of skin to aging. One of the factors contributing to skin aging is considered to be low resistance to aging. Therefore, the SNPs selected in this invention are SNPs that have a large influence on skin resistance to aging. The skin resistance to aging, which is the result of the analysis of the SNPs selected in this way, is an evaluation item that corresponds to the genetic background. By evaluating skin resistance to aging based on the SNPs selected in this invention, not only are valid evaluation results obtained, but it is also possible to highlight that low resistance can be compensated for by lifestyle habits. This can alleviate consumers' resignation due to genetic factors and provide new value to SNP analysis. When evaluating resistance to skin aging, dividing skin aging into multiple groups allows for the evaluation of the resistance to aging in each group. Therefore, this invention relates to the following:
[0006] [1] A method for determining skin resistance to aging based on SNPs in genes involved in resistance to skin aging. [2] The method according to item 1, wherein the skin aging is selected from aging caused by lifestyle, aging caused by the external environment, and natural aging caused by aging. [3] The method according to item 1 or 2, wherein the resistance to skin aging is at least one selected from the group consisting of cell activation ability, skin shielding ability, facial shape modeling ability, metabolic maintenance ability, skin tone assist ability, irritation protection ability, damage control ability, aquavitamin utilization ability, and oil vitamin utilization ability. [4] The method according to item 2 or 3, wherein cellular activity is determined based on a SNP in at least one gene selected from the group consisting of bleomycin hydrolase (BLMH), caspase 14 (CASP14), and hyaluronic acid synthase 3 (HAS3). [5] The following are examples of the resistance to skin aging: The method according to item 4, wherein the resistance to skin aging in relation to cellular activity is determined by at least one SNP selected from the group consisting of rs1050565, rs1552472, rs2129785, rs2158467, rs2232227, rs2232228, rs3103308, rs3181162, rs3190884, rs3759981, rs3785079, rs717309, and rs8110862. [6] The method according to item 2 or 3, wherein the skin shielding ability is determined based on a SNP in at least one gene selected from the group consisting of PLAU(uPA) and CASP14. [7] The following are examples of the resistance to skin aging: The method according to item 6, wherein the resistance of the skin to aging with respect to skin shielding ability is determined by at least one SNP selected from the group consisting of rs2158467, rs2227564, rs2227566, rs2227568, rs2227574, rs3181162, rs4065, rs717309, and rs8110862. [8] The method according to item 2 or 3, wherein the facial shape modeling ability is determined based on a SNP in at least one gene selected from the group consisting of MMP-1, MMP-2, MMP-9, ELN, HAS2, FBLN5, and COL1A1. [9] The aforementioned resistance to skin aging includes rs1799750, rs10233395, rs1030868, rs1057297, rs1057308, rs1061237, rs1061947, rs1107946, rs1144391, rs13925, rs13969, rs17576, rs17577, rs17804735, rs17855988, rs17884110, rs1800012, rs1871884, rs2046571, rs2071 The method according to item 8, wherein the resistance to skin aging with respect to facial shape modeling ability is determined by at least one SNP selected from the group consisting of 307, rs2241145, rs2246416, rs2285053, rs2287074, rs2430347, rs2856728, rs4255143, rs4618701, rs470558, rs5854, rs7149187, rs7201, rs77357345, rs8326, and rs9509.
[10] The method according to item 2 or 3, wherein metabolic maintenance capacity is determined based on a SNP in at least one gene selected from the group consisting of VEGFA and VEGFC.
[11] The following are examples of the resistance to skin aging: The method according to item 10, wherein the resistance of the skin to aging in relation to metabolic maintenance is determined by at least one SNP selected from the group consisting of rs1485766, rs10434, rs2010963, rs475106, rs475920, rs510684, rs699947, rs735286, and rs833061.
[12] The method according to item 2 or 3, wherein the skin tone assisting ability is determined based on a SNP in at least one gene selected from the group consisting of OCA2 and IRF4.
[13] The following are examples of the resistance to skin aging: The method according to item 12, wherein the resistance to skin aging with respect to skin tone assisting ability is determined by at least one SNP selected from the group consisting of rs1800414, rs1050975, rs1131442, rs12203592, rs12913832, rs1540771, rs1800404, rs1800411, rs74653330, and rs872071.
[14] The method according to item 2 or 3, wherein the stimulus protection is determined based on a SNP in at least one gene selected from the group consisting of SOD2 and GPX1.
[15] If the resistance to skin aging is irritation protection, then: The method according to item 14, wherein the resistance of the skin to aging in terms of irritation protection is determined by at least one SNP selected from the group consisting of rs4880, rs10370, rs1050450, rs1800668, rs3448, rs3811699, rs732498, rs7855, rs8031, and rs8179164.
[16] The method according to item 2 or 3, wherein the damage control capacity is determined based on a SNP in at least one gene selected from the group consisting of TNF-α, PLAU(uPA), and TNFR2.
[17] The following are examples of the resistance to skin aging: The method according to item 16, wherein the resistance to skin aging with respect to damage control ability is determined by at least one SNP selected from the group consisting of rs1799724, rs1061622, rs1800629, rs2227564, rs2227566, rs2227568, rs2227574, rs235249, rs3093662, rs3397, rs361525, rs4065, rs472093, rs474247, and rs673.
[18] The method according to item 2 or 3, wherein aquavitamin utilization is determined based on a SNP in at least one gene selected from a group of genes related to the control of vitamin B2 and vitamin B12 levels in the blood.
[19] The following are examples of the resistance to skin aging: The method according to item 18, wherein the resistance to skin aging related to aquavitamin utilization is determined by at least one SNP selected from the group consisting of rs1801133, rs1047781, rs10515552, rs2298585, and rs3760776.
[20] The method of item 2 or 3, wherein the oil vitamin utilization capacity is determined based on an SNP in at least one gene selected from a group of genes related to the control of vitamin A, vitamin D, and vitamin E levels in the blood.
[21] The following are examples of the resistance to skin aging: The method according to item 20, wherein the resistance to skin aging related to oil vitamin utilization is determined by at least one SNP selected from the group consisting of rs10882272, rs11057830, rs11234027, rs12272004, rs12785878, rs12934922, rs1667255, rs1993116, rs2060793, rs2108622, rs2282679, rs7501331, and rs964184.
[22] A method for suggesting preventive measures against aging in accordance with the resistance determined by the method described in any one of items 1 to 21.
[23] The method according to item 22, which determines multiple resistances selected from the group consisting of cell activation ability, skin shielding ability, facial shape modeling ability, metabolic maintenance ability, skin tone assist ability, irritation protection ability, damage control ability, aquavitamin utilization ability, and oil vitamin utilization ability, and proposes a corresponding preventive measure for at least one resistance that is determined to be weak.
[24] A determining mechanism for the resistance of the skin to aging, An input section for inputting SNP information about genes involved in resistance to skin aging. A memory unit that has pre-stored the relationship between SNP information and resistance to skin aging, A processing unit compares SNP information input from the input unit with SNP information previously stored in the memory unit and the relationship between these and the resistance to skin aging, and determines the resistance to skin aging. Output unit that outputs the determined resistance to skin aging. The determination device, including the aforementioned determination device.
[25] The determination device according to item 24, wherein the resistance to skin aging is at least one selected from the group consisting of cell activation ability, skin shielding ability, facial shape modeling ability, metabolic maintenance ability, skin tone assist ability, irritation protection ability, damage control ability, aquavitamin utilization ability, and oil vitamin utilization ability.
[26] The genes involved in cellular activity are at least one gene selected from the group consisting of BLMH, CASP14, and HAS3. The gene involved in skin shielding ability is at least one gene selected from the group consisting of PLAU(uPA) and CASP14. The genes involved in facial shape modeling ability are at least one gene selected from the group consisting of MMP-1, MMP-2, MMP-9, ELN, HAS2, FBLN5, and COL1A1. The genes involved in maintaining metabolism are at least one gene selected from the group consisting of VEGFA and VEGFC. The gene involved in assisting skin tone is at least one gene selected from the group consisting of OCA2 and IRF4. The gene involved in stimulus protection is at least one gene selected from the group consisting of SOD2 and GPX1. The genes involved in damage control are at least one gene selected from the group consisting of TNF-α, PLAU(uPA), and TNFR2. The determination device according to item 25, wherein the gene involved in aquavitamin utilization is at least one gene selected from the group consisting of genes related to the control of vitamin B2 and vitamin B12 levels in the blood, and the gene involved in oilvitamin utilization is at least one gene selected from the group consisting of genes related to the control of vitamin A, vitamin D, and vitamin E levels in the blood.
[27] SNP information for genes involved in cellular activity is as follows: This information pertains to at least one SNP selected from the group consisting of rs1050565, rs1552472, rs2129785, rs2158467, rs2232227, rs2232228, rs3103308, rs3181162, rs3190884, rs3759981, rs3785079, rs717309, and rs8110862. SNP information regarding genes involved in skin shielding ability is as follows: This information pertains to at least one SNP selected from the group consisting of rs1050565, rs1552472, rs2129785, rs2158467, rs2232227, rs2232228, rs3103308, rs3181162, rs3190884, rs3759981, rs3785079, rs717309, and rs8110862. SNP information for genes involved in facial shape modeling ability is as follows: Information about at least one SNP selected from the group consisting of rs1799750, rs10233395, rs1030868, rs1057297, rs1057308, rs1061237, rs1061947, rs1107946, rs1144391, rs13925, rs13969, rs17576, rs17577, rs17804735, rs17855988, rs17884110, rs1800012, rs1871884, rs2046571, rs2071307, rs2241145, rs2246416, rs2285053, rs2287074, rs2430347, rs2856728, rs4255143, rs4618701, rs470558, rs5854, rs7149187, rs7201, rs77357345, rs8326, and rs9509, SNP information about genes involved in metabolic maintenance ability is as follows: Information about at least one SNP selected from the group consisting of rs1485766, rs10434, rs2010963, rs475106, rs475920, rs510684, rs699947, rs735286, and rs833061, SNP information about genes involved in skin color assist ability is as follows: Information about at least one SNP selected from the group consisting of rs1800414, rs1050975, rs1131442, rs12203592, rs12913832, rs1540771, rs1800404, rs1800411, rs74653330, and rs872071, SNP information about genes involved in stimulus protection ability is as follows: Information about at least one SNP selected from the group consisting of rs4880, rs10370, rs1050450, rs1800668, rs3448, rs3811699, rs732498, rs7855, rs8031, and rs8179164, SNP information about genes involved in damage control ability is as follows: Information about at least one SNP selected from the group consisting of rs1799724, rs1061622, rs1800629, rs2227564, rs2227566, rs2227568, rs2227574, rs235249, rs3093662, rs3397, rs361525, rs4065, rs472093, rs474247, and rs673, SNP information about genes involved in aquavitamin activity is as follows: Information about at least one SNP selected from the group consisting of rs1801133, rs1047781, rs10515552, rs2298585, and rs3760776, SNP information about genes involved in oil vitamin activity is as follows: The determination device according to item 25 or 26, which is information about at least one SNP selected from the group consisting of rs10882272, rs11057830, rs11234027, rs12272004, rs12785878, rs12934922, rs1667255, rs1993116, rs2060793, rs2108622, rs2282679, rs7501331, and rs964184.
[28] The storage unit further stores preventive measures according to the resistance to skin aging, The processing unit reads out from the storage unit preventive measures according to the resistance determined in the processing unit, The output unit outputs the read preventive measures. The determination device according to any one of items 24 to 27.
[29] The processing unit of the determination device determines a plurality of resistances selected from the group consisting of cell active force, skin shield force, face shape modeling force, metabolism maintenance force, skin color assist force, stimulus protection force, damage control force, aquavitamin activity force, and oil vitamin activity force, and the output unit of the determination device outputs preventive measures corresponding to at least one resistance determined to have low resistance. The determination device according to item 28.
[30] A program for causing a computer including an input unit, a memory unit, a processing unit, and an output unit to determine the resistance to skin aging, the following: A command is issued to the processing unit to compare the SNP information about genes involved in resistance to skin aging, input from the input unit, with the relationship between SNP information previously stored in the memory unit and resistance to skin aging, and to determine the resistance to skin aging; A command is output from the output unit to determine the resistance level to skin aging. The program, including the program.
[31] The program according to item 30, wherein the resistance to skin aging is at least one selected from the group consisting of cell activation ability, skin shielding ability, facial shape modeling ability, metabolic maintenance ability, skin tone assist ability, irritation protection ability, damage control ability, aquavitamin utilization ability, and oilvitamin utilization ability.
[32] The genes involved in cellular activity are at least one gene selected from the group consisting of BLMH, CASP14, and HAS3. The gene involved in skin shielding ability is at least one gene selected from the group consisting of PLAU(uPA) and CASP14. The genes involved in facial shape modeling ability are at least one gene selected from the group consisting of MMP-1, MMP-2, MMP-9, ELN, HAS2, FBLN5, and COL1A1. The genes involved in maintaining metabolism are at least one gene selected from the group consisting of VEGFA and VEGFC. The gene involved in assisting skin tone is at least one gene selected from the group consisting of OCA2 and IRF4. The gene involved in stimulus protection is at least one gene selected from the group consisting of SOD2 and GPX1. The genes involved in damage control are at least one gene selected from the group consisting of TNF-α, PLAU(uPA), and TNFR2. The gene involved in the utilization of aquavitamins is at least one gene selected from the group consisting of genes related to the control of vitamin B2 and vitamin B12 levels in the blood. The program according to item 31, wherein the gene involved in the utilization of oil vitamins is at least one gene selected from the group consisting of genes related to the control of vitamin A level, vitamin D level, and vitamin E level in the blood.
[33] SNP information for genes involved in cellular activity is as follows: This information pertains to at least one SNP selected from the group consisting of rs1050565, rs1552472, rs2129785, rs2158467, rs2232227, rs2232228, rs3103308, rs3181162, rs3190884, rs3759981, rs3785079, rs717309, and rs8110862. SNP information regarding genes involved in skin shielding ability is as follows: This information pertains to at least one SNP selected from the group consisting of rs1050565, rs1552472, rs2129785, rs2158467, rs2232227, rs2232228, rs3103308, rs3181162, rs3190884, rs3759981, rs3785079, rs717309, and rs8110862. SNP information for genes involved in facial shape modeling ability is as follows: rs1799750, rs10233395, rs1030868, rs1057297, rs1057308, rs1061237, rs1061947, rs1107946, rs1144391, rs13925, rs13969, rs17576, rs17577, rs17804735, rs17855988, rs17884110, rs1800012, rs1871884, rs20465 Information about at least one SNP selected from the group consisting of 71, rs2071307, rs2241145, rs2246416, rs2285053, rs2287074, rs2430347, rs2856728, rs4255143, rs4618701, rs470558, rs5854, rs7149187, rs7201, rs77357345, rs8326, and rs9509, SNP information for genes involved in metabolic maintenance is as follows: This information pertains to at least one SNP selected from the group consisting of rs1485766, rs10434, rs2010963, rs475106, rs475920, rs510684, rs699947, rs735286, and rs833061. SNP information for genes involved in skin tone assisting ability is as follows: At least one SNP selected from the group consisting of rs1800414, rs1050975, rs1131442, rs12203592, rs12913832, rs1540771, rs1800404, rs1800411, rs74653330, and rs872071 This is information about, SNP information for genes involved in stimulus protection is as follows: This information pertains to at least one SNP selected from the group consisting of rs4880, rs10370, rs1050450, rs1800668, rs3448, rs3811699, rs732498, rs7855, rs8031, and rs8179164. SNP information for genes involved in damage control is as follows: This information pertains to at least one SNP selected from the group consisting of rs1799724, rs1061622, rs1800629, rs2227564, rs2227566, rs2227568, rs2227574, rs235249, rs3093662, rs3397, rs361525, rs4065, rs472093, rs474247, and rs673. SNP information regarding genes involved in aquavitamin utilization is as follows: This information pertains to at least one SNP selected from the group consisting of rs1801133, rs1047781, rs10515552, rs2298585, and rs3760776. SNP information regarding genes involved in the utilization of oil vitamins is as follows: The program described in item 31 or 32, which is information about at least one SNP selected from the group consisting of rs10882272, rs11057830, rs11234027, rs12272004, rs12785878, rs12934922, rs1667255, rs1993116, rs2060793, rs2108622, rs2282679, rs7501331, and rs964184.
[34] The program described above is: A command to store in the memory unit preventive measures corresponding to the skin's resistance to aging, A command to operate the processing unit to read out from the storage unit the preventive measures corresponding to the resistance force determined in the processing unit, The output unit is given a command to output the read action. The program described in any one of items 30-33, including further details.
[35] The program gives a command to the computer to determine a plurality of resistances selected from the group consisting of cell activation power, skin shielding power, facial shape modeling power, metabolic maintenance power, skin tone assist power, irritation protection power, damage control power, aqua vitamin utilization power, and oil vitamin utilization power. A command is issued to the output unit to output a corresponding preventive action for at least one resistance level that the processing unit has determined to be low. The programs listed in item 34, including those listed in item 34. [Effects of the Invention]
[0007] By evaluating the results of SNP analysis from the perspective of resistance to aging, it becomes possible to make appropriate assessments according to genetic background, and to propose appropriate preventive measures to supplement resistance. [Brief explanation of the drawing]
[0008] [Figure 1] Figure 1A is a schematic diagram of an information processing device comprising an input unit, a storage unit, a processing unit, and an output unit. Figure 1B is a schematic diagram of a system in which the information processing device operates via a network. [Figure 2A-B] Figures 2A and 2B are schematic diagrams illustrating the process by which the information processing device of the present invention determines the resistance of skin to aging according to a program. [Figure 2C-D] Figures 2C to 2D are schematic diagrams illustrating the process by which the information processing device of the present invention determines the resistance of skin to aging according to a program. [Figure 3] Figure 3 shows a graph that classifies subjects into high-value and low-value groups based on their skin condition (wrinkle) measurements, dividing them into a high-value group and a low-value group. [Figure 4] Figure 4 is a graph of the ROC curve showing the relationship between sensitivity and specificity, created during the validation of a learning model for determining skin type. [Modes for carrying out the invention]
[0009] The present invention relates to a method for determining a subject's resistance to skin aging based on their SNP information. The subject's SNP information can include information on one or more SNPs in genes involved in resistance to skin aging.
[0010] Skin condition changes with age, and the degree of skin aging is influenced by genetic background. Skin condition changes with age in areas such as age spots, wrinkles, skin elasticity, melanin levels, skin brightness, yellowness, and upper arm skin color. Skin resistance to aging refers to the ability to slow down the progression of aging, and this varies depending on genetic background. In other words, the progression of aging is influenced by the accumulation of changes that occur within the body in daily life, represented by aging, as well as by external environmental factors such as ultraviolet rays and dryness. Resistance to these internal and external factors that promote skin aging differs from person to person depending on their genetic background. Therefore, knowing skin resistance to aging based on genetic background means knowing resistance to the effects of acquired internal and external factors that promote skin aging. Since internal and external factors that promote skin aging have a wide range of effects on the skin, an individual's skin resistance to aging is determined by setting a skin aging resistance that affects skin responsiveness and summing it up for each individual. In this invention, the resistance to skin aging determined based on the subject's SNP information refers to the resistance to skin aging based on genetic background.
[0011] Acquired factors that influence skin aging include internal lifestyle habits such as stress and poor nutritional status, as well as external factors such as ultraviolet radiation and dryness. When resistance to skin aging is low, as assessed by genetic background, it is possible to slow down skin aging by changing acquired environmental factors, i.e., lifestyle habits and the external environment. Lifestyle habits that are involved in skin aging include diet, sleep rhythm, excessive or insufficient exercise. External environmental factors that are involved in skin aging include ultraviolet radiation, pollutants, gravity, and changes in temperature and humidity in living spaces.
[0012] If SNP analysis reveals low resistance to skin aging caused by lifestyle habits, lifestyle improvements can be advised. Furthermore, if SNP analysis reveals low resistance to skin aging caused by external environmental factors, preventative measures to mitigate the effects of the external environment, such as UV protection, protection against pollutants, and gravity-related care like massage, can be implemented. By classifying skin aging into different types and evaluating the corresponding resistance to that type of aging, appropriate treatments can be provided for each specific type of skin aging.
[0013] In this invention, the SNPs involved in determining the resistance of skin to aging are those adopted in a skin aging model formula established by machine learning the relationship between the subject's genetic and environmental information regarding SNPs and measurement data of skin condition. From the SNPs adopted in the skin aging model formula, genes involved in skin function are identified through dermatological research, and genes involved in resistance to aging are selected and grouped according to their function. SNPs that influence the function of the genes selected through this selection process can show resistance to skin aging with respect to the grouped function.
[0014] The SNPs used in this invention are as follows: rs1050565、rs8110862、rs2232228、rs2227564、rs1799750、rs7201、rs17577、rs8326、rs2046571、rs2246416、rs1107946、rs2010963、rs1485766、rs1800414、rs1540771、rs4880、rs1050450、rs1799724、rs1061622、rs1801133、rs2298585、rs10882272、rs2282679、rs2108622、rs1552472、rs2158467、rs3785079、rs4065、rs5854、rs2241145、rs9509、rs2071307、rs1057308、rs7149187、rs1057297、rs833061、rs475106、rs74653330、rs12203592、rs7855、rs3448、rs1800629、rs3397、rs1047781、rs1667255、rs11234027、rs964184、rs2129785、rs3181162、rs2232227、rs2227566、rs470558、rs1030868、rs13925、rs2856728、rs1871884、rs2430347、rs1061237、rs699947、rs12913832、rs872071、rs8031、rs1800668、rs361525、rs235249、rs3760776、rs12934922、rs12785878、rs11057830、rs3103308、rs717309、rs3759981、rs2227568、rs1144391、rs2285053、rs13969、rs10233395、rs4255143、rs17804735、rs1061947、rs10434、rs475920、rs1800404、rs1050975、rs10370、rs3811699、rs673、rs472093、rs10515552、rs7501331、rs1993116、rs12272004、rs3190884、rs2227574、rs17884110、rs2287074、rs17576、rs17855988、rs4618701、rs77357345、rs1800012、rs735286、rs510684、rs1800411、At least one selected from the group consisting of rs1131442, rs732498, rs8179164, rs3093662, rs474247, and rs2060793 may be used. Among the enumerated SNPs, any selection may be made depending on the resistance to aging of the skin being evaluated.
[0015] In one aspect of the present invention, the resistance to skin aging in the present invention is at least one resistance selected from the group consisting of cell activation ability, skin shielding ability, facial shape modeling ability, metabolic maintenance ability, skin tone assisting ability, irritation protection ability, damage control ability, aquavitamin utilization ability, and oil vitamin utilization ability.
[0016] Cellular activity can also be described as moisturizing ability, anti-aging moisturizing ability, cellular homeostasis ability, cellular environment maintenance ability, cellular metabolic regulation ability, skin metabolic ability, and skin hydration ability, and it is the ability to enhance the function of properly maintaining moisture in the stratum corneum of the skin. By properly maintaining moisture in the stratum corneum of the skin, the function of enzymes within the stratum corneum is maintained, and skin metabolism and homeostasis are maintained. Furthermore, moisture in the stratum corneum of the skin also contributes to skin flexibility and mitigates the effects of changes in the shape of the skin surface caused by facial expressions, etc. This important moisture in the stratum corneum of the skin can be enhanced by increasing the production of natural moisturizing factors (NMF), thereby normalizing epidermal differentiation and enhancing barrier function. Examples of genes involved in cellular activity include bleomycin hydrolase (BLMH), caspase 14 (CASP14), and hyaluronic acid synthase 3 (HAS3). As SNPs involved in cellular activity, at least one selected from the group consisting of: rs1050565, rs1552472, rs2129785, rs3103308, rs3190884, rs8110862, rs2158467, rs3181162, rs717309, rs2158467, rs2232228, rs3785079, rs2232227, rs3759981, and rs3785079 may be used. In one embodiment, any combination, and possibly all, of such SNPs can be used to determine the resistance to skin aging due to moisturizing ability. The relationship between each SNP and the gene is shown in the table below. [Table 1]
[0017] Skin shielding power can also be described as barrier power, anti-aging barrier defense power, skin wrapping power, skin internal stabilization power, skin gate power, and skin gate-keeping power. It is the ability to maintain a good barrier function that prevents moisture from leaking out of the skin and prevents harmful substances from easily entering from the outside. Good barrier function is maintained by normalizing epidermal differentiation and ensuring that the stratum corneum is properly constructed. Genes involved in skin shielding power include urokinase-type plasminogen activator (uPA) and caspase 14 (CASP14). As SNPs involved in skin shielding power, at least one selected from the group consisting of the following: rs2227564, rs4065, rs2227566, rs2227568, rs2227574, rs8110862, rs2158467, rs3181162, rs717309, and rs2158467 may be used. In one embodiment, any combination, and possibly all, of such SNPs can be used to determine the skin's resistance to aging related to its barrier function. The relationship between each SNP and the gene is shown in the table below. [Table 2]
[0018] Facial shape modeling ability can also be described as internal skin structure ability, facial shaping ability, firming ability, and skin form ability, and its components are anti-aging dermis-epidermal coordination ability and anti-aging dermal elasticity assist ability. Anti-aging dermis-epidermal coordination ability can also be described as skin layer maintenance ability and skin communication ability, and refers to the ability to maintain the basement membrane at the boundary between the epidermis and dermis in good condition and to improve skin function. Furthermore, anti-aging dermal elasticity assist ability can also be described as skin spring adjustment ability and skin spring power, and refers to the ability to maintain the dermal structure that maintains skin elasticity. Genes involved in facial shape modeling ability include matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), elastin (ELN), hyaluronic acid synthase 2 (HAS2), fibrin 5 (FBLN5), and type I collagen (COL1A1). The following SNPs are related to facial shape modeling capabilities: rs1799750, rs5854, rs470558, rs1144391, rs17884110, rs7201, rs2241145, rs1030868, rs2285053, rs2287074, rs17577, rs9509, rs13925, rs13969, rs17576, rs8326, rs2071307, rs2856728, rs10233 At least one selected from the group consisting of 395, rs17855988, rs2046571, rs1057308, rs1871884, rs4255143, rs4618701, rs2246416, rs7149187, rs2430347, rs17804735, rs77357345, rs1107946, rs1057297, rs1061237, rs1061947, and rs1800012 may be used. In one embodiment, any combination, and possibly all, of such SNPs can be used to determine resistance to aging due to anti-aging dermal-epidermal synergistic force and anti-aging dermal elasticity assist force. The relationship between each SNP and the gene is shown in the table below. [Table 3]
[0019] Metabolic maintenance ability can also be described as circulation ability, anti-aging circulatory regulation ability, circulation support ability, circulatory maintenance ability, holistic coordination ability, and skin nutrient supply ability, and is the ability to improve the blood vessels that replenish nutrients and the lymph that remove waste products. Genes involved in metabolic maintenance ability include vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor C (VEGFC). As SNPs involved in metabolic maintenance ability, at least one selected from the group consisting of the following: rs2010963, rs833061, rs699947, rs10434, rs735286, rs1485766, rs475106, rs475106, rs475920, and rs510684 may be used. In one embodiment, any combination, and possibly all combinations, of such SNPs can be used to determine resistance to aging caused by blood vessels and lymph. The relationship between each SNP and the gene is shown in the table below. [Table 4]
[0020] Skin tone assisting power can also be called skin tone adjustment power, anti-aging skin tone adjustment power, UV filtering power, skin tone maintenance power, UV response power, and photoaging resistance power, and is the ability to maintain high levels of melanin, which has a natural UV protection function in the skin. Genes involved in skin tone assisting power include oculocutaneous albinism type II (OCA2) and interferon regulator (IRF4). As SNPs involved in skin tone assisting power, at least one selected from the group consisting of the following: rs1800414, rs74653330, rs12913832, rs1800404, rs1800411, rs1540771, rs12203592, rs872071, rs1050975, and rs1131442 may be used. In one embodiment, any combination, and possibly all combinations, of such SNPs can be used to determine resistance to aging caused by melanin. The relationship between each SNP and the gene is shown in the table below. [Table 5]
[0021] Stimulus protection power can also be described as antioxidant power, anti-aging oxidation power, stimuli scavenging power, stimuli soothing power, damage blocking power, and damage absorption power, and is the power to neutralize and remove reactive oxygen species generated in the skin. Reactive oxygen species are removed within cells by the action of enzymes such as superoxide dismutase and glutathione peroxidase. Genes involved in stimulus protection power include superoxide dismutase-2 (SOD2) and glutathione peroxidase 1 (GPX1). As SNPs involved in stimulus protection power, at least one selected from the group consisting of the following: rs4880, rs7855, rs8031, rs10370, rs732498, rs1050450, rs3448, rs1800668, rs3811699, and rs8179164 may be used. In one embodiment, any combination, and possibly all, of such SNPs can be used to determine resistance to aging due to anti-aging oxidative capacity. The relationship between each SNP and the gene is shown in the table below. [Table 6]
[0022] Damage control ability can also be described as inflammation regulation ability, anti-aging and anti-inflammatory ability, inflammation control ability, skin internal calming ability, damage extinguishing ability, and skin attack regulation ability, and is the ability to reduce or suppress the production of inflammatory factors in the skin. By reducing inflammatory factors, inflammation can be suppressed. Genes involved in damage control ability include tumor necrosis factor α (TNFα), urokinase-type plasminogen activator (PLAU (uPA)), and tumor necrosis factor receptor 2 (TNFR2). As SNPs related to damage control, at least one selected from the group consisting of the following: rs1799724, rs1800629, rs361525, rs673, rs3093662, rs2227564, rs4065, rs2227566, rs2227568, rs2227574, rs1061622, rs3397, rs235249, rs472093, and rs474247 may be used. In one embodiment, any combination, and possibly all, of such SNPs can be used to determine resistance to aging caused by inflammation. The relationship between each SNP and the gene is shown in the table below. [Table 7]
[0023] Aquavitamin utilization ability can also be described as anti-aging water-soluble vitamin control ability, aquavitamin optimization ability, or aquavitamin regulation ability, and is the ability to normalize the blood concentration of water-soluble vitamins. Genes involved in aquavitamin utilization ability include those that affect the control of blood levels of vitamin B2 and vitamin B12. As SNPs involved in aquavitamin utilization ability, at least one selected from the group consisting of the following:rs1801133, rs2298585, rs1047781, rs3760776, rs10515552, and rs3760776 may be used. In one embodiment, any combination, and possibly all, of such SNPs can be used to determine resistance to aging caused by blood aquavitamin concentration. The relationship between each SNP and the gene is shown in the table below. [Table 8]
[0024] Oil vitamin utilization ability can also be described as the ability to control anti-aging fat-soluble vitamins, optimize oil vitamin levels, or regulate oil vitamin levels, and is the ability to normalize the blood concentration of fat-soluble vitamins. Genes involved in oil vitamin utilization ability include those that affect the control of blood levels of vitamins A, D, and E. As SNPs involved in oil vitamin utilization ability, at least one selected from the group consisting of the following: rs10882272, rs1667255, rs12934922, rs7501331, rs2282679, rs11234027, rs12785878, rs1993116, rs2060793, rs2108622, rs964184, rs11057830, and rs12272004 may be used. In one embodiment, any combination, and possibly all, of such SNPs can be used to determine resistance to aging caused by blood oil vitamin levels. The relationship between each SNP and the gene is shown in the table below. [Table 9]
[0025] In another aspect of the present invention, the following: SNP information input section, A memory unit that has pre-stored the relationship between SNP information and resistance to skin aging, A processing unit that compares SNP information input from the input unit with SNP information previously stored in the memory unit and the relationship with the resistance to skin aging, and determines the resistance to skin aging, and Output unit that outputs the determined resistance to skin aging. This invention relates to a device for determining the resistance of skin to aging, including the SNP information used in the determination device of the present invention. The SNP information used in the determination device of the present invention may be the same as the SNP information used in the method of the present invention.
[0026] In yet another aspect, the present invention relates to a program for causing a computer to determine the resistance to skin aging, comprising: an input unit, a storage unit, a processing unit, and an output unit, the following: A command to the processing unit to compare the SNP information input from the input unit with the relationship between the SNP information previously stored in the memory unit and the resistance to skin aging, and to determine the resistance to skin aging; and A command is output from the output unit to determine the resistance level to skin aging. This also relates to programs, including the present invention. The SNP information used in the program of the present invention may be the same as the SNP information used in the method of the present invention.
[0027] In the method, determination device, and program of the present invention, when determining resistance to skin aging, a score can be determined for each selected SNP for each resistance to aging based on its genotype (major homozygous: Homo1, heterozygous: Hetero, minor homozygous: Homo2). The correspondence between the major homozygous type (Homo1) of each gene's SNP, its phenotype, and its genetic model is shown in the table below. [Table 10]
[0028] If a gene SNP increases resistance in the major homozygous type, it is denoted as Homo1: High; if it decreases resistance, it is denoted as Homo1: Low. For heterozygous types, the skin constitution results obtained from the association study between skin type and gene SNPs are used to calculate the frequency of the four genetic models (Dominant, Recessive, Additive, Multiplicative) selected for each SNP, and the model that appears most frequently is adopted. A score can be arbitrarily determined according to the strength of resistance in each model. As an example, for a SNP that decreases resistance in the major homozygous type, the resistance in each genetic model is shown in the table below and scored accordingly. [Table 11]
[0029] The method, determination device, and / or program of the present invention can determine at least one resistance to skin aging selected from the group consisting of cell activation power, skin shielding power, facial shape modeling power, metabolic maintenance power, skin tone assist power, irritation protection power, damage control power, aquavitamin utilization power, and oilvitamin utilization power. The method, determination device, and / or program of the present invention can determine multiple resistances to skin aging from among the above-mentioned resistances to skin aging. More preferably, it can determine 2, 3, 4, 5, 6, 7, 8, or 9 resistances to skin aging. Depending on the resistance to aging determined by the method, determination device, and / or program of the present invention, preventive measures against aging can be provided. From among the multiple determined resistances to skin aging, more preferably, preventive measures can be provided by selecting in order from the lowest score for resistance to aging. If the scores are the same, the resistance to aging to be selected can be determined based on the results of a separately obtained questionnaire. The resistance to aging thus displayed is a genetically weak resistance and therefore requires priority in countermeasures.
[0030] In this invention, SNPs are represented by their rs number (Reference SNP ID number). Detailed information about each SNP corresponding to each rs number (location on the chromosome and mutations) is managed by the National Center for Biotechnology Information (NCBI) in the United States, and can be found on the NCBI website. http: / / www.ncbi.nlm.nih.gov / ) is available for reference.
[0031] SNP detection may be performed by any known method. For example, nucleic acids from a subject's biological sample, such as saliva, blood, mucous membrane, tissue fragment, or hair, are purified according to a standard method, and SNPs are detected in the purified nucleic acids. Therefore, the method for determining skin characteristics of the present invention may further include a sample preparation step and a nucleic acid purification step. The nucleic acid may be DNA or RNA, and in the case of RNA, it is preferable to perform reverse transcription after purification to prepare DNA. In the SNP detection step, any method that enables the detection of SNPs in the purified nucleic acids can be used. SNPs can be detected by sequencing around the location of the target SNP, or by using PCR-based methods, DNA probe-based methods, or mass spectrometry-based methods. Examples of PCR-based methods include SNP typing, TaqMan PCR, single-nucleotide extension, pyrosequencing, and exonuclease cycling assay. Examples of DNA probe-based methods include the DNA chip method (DNA microarray) and the Invader method (Comprehensive Gene Polymorphism Analysis (SNP), Japanese Journal of Pharmacology, 125, 148-152, 2005). SNPs may be associated with other SNPs in linkage disequilibrium. The target SNP can be detected by detecting SNPs in linkage disequilibrium with the target SNP. Therefore, in this invention, SNP detection is not limited to the direct detection of the target SNP, but also includes detecting the target SNP by detecting SNPs in linkage disequilibrium.
[0032] Furthermore, the presence of SNPs can also be detected based on an individual's already sequenced nucleotide sequence. In this case, the presence of SNPs can be detected by examining the sequence at the location where the SNP is located within the already determined nucleotide sequence data. Therefore, SNP detection in this case may be performed by inputting the nucleotide sequence data into a computer that stores SNP information. In a more preferred embodiment, the input is made from a terminal via the internet, the SNP is detected on a server, and the detection results can be output to the terminal via the internet.
[0033] Figure 1A shows a specific configuration of the decision-making device of the present invention, which comprises an input unit 11, a storage unit 12, a processing unit 13, and an output unit 14. The decision-making device of the present invention may be an information processing device 10, or it may form a system 20 connected to the information processing device 10 via a network (Figure 1B). The system 20 has a terminal 30 separate from the information processing device 10, which is connected to the information processing device 10 via a network. The connection between the terminal 30 and the information processing device 10 may be wired or wireless. For example, the connection may be made via an intranet or the internet.
[0034] The input unit 11 further includes an interface relating to any device that enables data input. The interface may connect to an operation unit such as a keyboard or mouse, a communication unit, or an external storage device such as a CD-ROM, DVD-ROM, BD-ROM, or Memory Stick. Information is input to the information processing device via the input unit 11. The information input from the input unit may include commands in addition to SNP information. Information regarding SNPs may be input from the input unit 11 and stored in the storage unit 12. Instead of information about SNPs, information about the target genetic sequence may be input from the input unit 11. The input sequence information may be temporarily stored in the storage unit 12, or it may be sent directly to the processing unit 13. The target genetic sequence information may be the entire genome sequence, only a portion of the target sequence, or only SNP information. Instructions for processing can be given from the input unit 11 to the processing unit 13 via the operation unit.
[0035] The storage unit 12 is any device for storing data, such as memory devices like RAM, ROM, and flash memory; fixed disk devices like hard disk drives; or portable storage devices like flexible disks and optical disks. The storage unit 12 stores data and instructions input from the input unit 11, programs used for various computer processes, processing results from the processing unit 13, a database, and forms to be output to the output unit 14. Computer programs may be installed, for example, on computer-readable recording media such as CD-ROMs and DVD-ROMs, or via the Internet. Computer programs are installed in the storage unit 12 using a known setup program or the like. The storage unit 12 stores the relationship between SNP information and skin resistance to aging. It also stores a table or formula for scoring skin resistance to aging. The relationship between the score and preventive measures for skin resistance to aging may also be stored. The storage unit 12 may also store information about the results of questionnaires regarding skin concerns.
[0036] The processing unit 13 is any device that performs arithmetic processing and typically has one or more processors or their peripheral circuits. The processing unit 13 comprehensively controls the overall operation of the information processing device 10 and is, for example, a central processing unit (CPU). The processing unit 13 executes various arithmetic processes according to the program stored in the memory unit 12. The arithmetic processing is performed by the processor included in the processing unit 13. This processor includes a functional module that controls the input unit 11, the memory unit 12, and the output unit 14, and can perform various controls. Each of these parts may be composed of an independent integrated circuit, microprocessor, firmware, etc. The processing unit 13 reads the SNP information input from the input unit 11 and the relationship between the SNP information stored in the memory unit 12 and the resistance to skin aging, and determines the resistance to skin aging. The determination of resistance may be made by reading a table or formula for scoring the resistance to skin aging stored in the memory unit 12 and scoring it. The processing unit 13 scores the resistance of multiple skin cells to aging, and can read from the memory unit 12 a predetermined number of low-scoring skin cell resistances, for example, 1, 2, 3, or 4, preferably 3, to determine preventive measures. If the scores are the same, the processing unit 13 can read the results of a separate questionnaire on skin concerns from the memory unit 12 and determine which of the same-scoring skin cell resistances to select. Specifically, it selects the skin cell resistance that is highly correlated with the skin concerns. The processing unit 13 can also be operated to detect the presence of SNPs in genetic sequence information when target genetic sequence information is input instead of SNP information. More specifically, the processing unit 13 can detect the presence of SNPs in target sequence information from SNP sequence information pre-stored in the memory unit 12 and target sequence information input from the input unit 11. Information about the presence of SNPs detected by the processing unit 13 may be temporarily stored in the memory unit 12.
[0037] The output unit 14 is any device capable of outputting the results of processing by the processing unit 13, such as a display device like a liquid crystal display that directly displays the results, or an output means like a printer, and may include an interface. It may also be connected to a communication unit for outputting via a network or to an external storage device via the interface. The communication unit used in the input unit 11 and the output unit 14 relates to a communication interface such as a LAN or port for connecting the information processing device to a network. The output unit 14 outputs the results processed by the processing unit 13, for example, the subject's resistance to skin aging. Furthermore, the output unit 14 outputs the subject's SNP information and preventive measures for those with low resistance to skin aging.
[0038] Based on the skin's resistance to aging output from the output unit 14, counseling can be provided. During counseling, preventive and strengthening measures can be offered according to the skin's resistance to aging. "According to the skin's resistance to aging" means providing measures that can supplement resistance when it is low. The relationship between skin's resistance to aging and preventive measures may be stored in the memory unit 12 in advance, and the output unit 14 can output information on preventive measures along with the output of skin's resistance to aging. Preventive measures may include cosmetics, ingredients, and beauty treatments such as frequency and method of use, as well as measures that change lifestyle habits and the external environment.
[0039] The present invention can provide preventive measures tailored to the resistance to aging of each skin type, as evaluated by the method, apparatus, or program of this invention. Such preventive measures can include not only cosmetic treatments such as products applied directly to the skin, such as cosmetics, and their usage methods, but also suggestions that include behaviors such as diet, sleep, exercise, bathing, and mental activity. For subjects evaluated as having weak cellular activity, measures to enhance cellular activity can be proposed. Such measures include measures to increase the water retention capacity of the stratum corneum, such as cosmetic treatments like face masks and esthetic treatments, products that enhance water retention, the use of humidifiers, exercise to improve blood circulation, and meditation that is effective for moisturizing. For subjects evaluated as having weak skin shielding ability, measures to enhance skin shielding ability can be proposed. Such measures include measures to reduce stress, such as aromatherapy, reviewing sleep duration and using products that promote recovery from fatigue, a diet rich in omega-3 oils and minerals, and gut health. For subjects evaluated as having weak facial shape modeling ability, measures to enhance facial shape modeling ability can be proposed. Such measures include facial muscle exercises such as massage and facial yoga, drinking collagen drinks and a diet rich in protein, and using products that avoid blue light. For subjects evaluated as having weak metabolic maintenance ability, treatments to enhance metabolic maintenance ability can be proposed. Such treatments include cosmetic procedures that promote blood circulation and improve lymphatic flow, exercise such as hot yoga and pressure training, a diet rich in ginger and vitamins A and E that promote blood circulation, and sleep methods that reduce swelling. For subjects evaluated as having weak skin tone support ability, treatments to enhance skin tone support ability can be proposed. Such treatments include the use of sun protection products such as sunscreens and parasols, a diet rich in green and yellow vegetables and nuts that prevent photoaging, and morning indoor sunbathing to regulate the rhythm. For subjects evaluated as having weak irritation protection ability, treatments to enhance irritation protection ability can be proposed. Such treatments include cosmetics with antioxidant effects, a diet rich in polyphenols and vitamin C, and slow jogging and lukewarm baths that increase the body's overall defense. For subjects evaluated as having weak damage control ability, treatments to enhance damage control ability can be proposed.Such measures include using anti-inflammatory cosmetics and turmeric-containing products, maintaining a balanced diet, and doing 10-minute exercises to prevent overall muscle weakness. For individuals assessed as having weak aquavitamin utilization, measures to enhance aquavitamin utilization can be proposed. Such measures include cosmetics and supplements containing vitamin derivatives, pork dishes, methods for regulating and monitoring the autonomic nervous system, and effective methods for vitamin intake after exercise. Similarly, for individuals assessed as having weak oil vitamin utilization, measures to enhance oil vitamin utilization can be proposed. Such measures include beta-carotene supplements, a diet utilizing fruits, fish, and mushrooms, proper sun exposure methods, and suggestions for products to avoid hay fever and air pollution.
[0040] All references made herein are incorporated herein by citation in their entirety.
[0041] The embodiments of the present invention described below are for illustrative purposes only and do not limit the technical scope of the invention. The technical scope of the invention is limited solely by the claims. Modifications to the invention, such as additions, deletions, and substitutions of constituent elements of the invention, can be made without departing from the spirit of the invention. [Examples]
[0042] Example 1: Subject of Analysis The study targeted 1448 female volunteers aged 20-79. Prior to the analysis, a questionnaire survey was conducted regarding age, height, weight, BMI (calculated from height and weight according to a standard method), UV exposure information, and smoking information. Regarding UV exposure information, current awareness of sunburn was classified into four stages (two stages of sunburn preference, and two stages of non-sunburn preference). Furthermore, to understand responses to UV rays in detail, sunburn prevention measures from birth to the present (1-14 years, 15-19 years, 20-24 years, 25-29 years, and thereafter in 10-year increments) were classified into three stages (actively taking no UV protection measures, UV protection measures for strong sunlight, and UV protection measures even for weak sunlight). Regarding smoking information, the participants were divided into three groups: no smoking history, a history of smoking 20 or more cigarettes per day in the past, and a history of smoking less than 20 cigarettes per day in the past.
[0043] Example 2: Acquisition of actual skin measurement data in the subject of analysis As skin characteristics, we measured the wrinkle condition, blemish condition, skin color (cheek melanin amount, brightness, yellowness, inner upper arm skin color), and elasticity of female volunteers aged 20 to 79 years. For wrinkle and blemish conditions, we used Visia Evolution (Canfield Scientific) to calculate the index values (blemish 1) of wrinkles and blemishes from the captured images using a dedicated analysis method. For blemishes, we also calculated the number of blemishes (blemish 2) and the area of blemishes (blemish 3) using a skin imaging device and used these for analysis. Skin color was analyzed using a spectrophotometer CM-700d (Konica Minolta), measuring the melanin amount (skin color 1), brightness (L*, color value) (skin color 2), and yellowness (b*, color value) (skin color 3) of the cheeks, and also measuring the inner upper arm skin color (skin color 4). Elasticity was measured using a commercially available dedicated device (Cutometer). For the wrinkles around the eyes, a silicone replica of the skin surface was created, 3D measurements were taken, the data was imported into a computer, and the image was processed using a proprietary analysis system to calculate the maximum depth, volume, and area of the wrinkles.
[0044] Example 3: Determination of SNPs in the subject of analysis Based on past dermatological findings, the following 79 SNPs were selected for analysis because they are expected to have an impact on skin characteristic values: rs1800629, rs2108622, rs1047781, rs12203592, rs16891982, rs3760776, rs9340799, rs12913832, rs17822931, rs96 4184, rs1801133, rs2228479, rs10515552, rs10741657, rs10882272, rs11057830, rs11234027, rs12272004, rs12377 462, rs12785878, rs12931267, rs1540771, rs1667255, rs1993116, rs2060793, rs2227564, rs2282679, rs2298585, rs 3829251, rs41281112, rs4654748, rs492602, rs602662, rs1030868, rs1126643, rs1256062, rs12934922, rs1485766, r s1501299, rs17577, rs1799724, rs1800012, rs1800414, rs2010963, rs2234693, rs2241145, rs2285053, rs2287074, r s2287076, rs2987983, rs3918242, rs4065, rs4252125, rs6152, rs7201, rs74653330, rs7501331, rs8110862, rs8326, r s833061, rs1050565, rs1799750, rs4880, rs1050450, rs6058017, rs1061622, rs2046571, rs2232228, rs3785079, rs2 246416, rs1107946, rs11568737, rs41303970, rs12051272, rs182052, rs3865188, rs6810075, rs7799039, rs1137101. The selection criteria included factors, enzymes, and extracellular matrix proteins that function in the epidermis, basement membrane, dermis, subcutaneous adipose tissue, and throughout the body (hormones, vitamins, etc.). From these, genes containing SNPs were selected as candidates. These SNPs are thought to potentially influence various skin traits. Next, for each of the 79 types of SNPs mentioned above, four types of genetic models were established: recessive models, dominant models, additive models, and synergistic models. A total of 316 genetic models were considered for each of the 79 SNPs, and these were used as genetic information. Using this genetic information and environmental information as explanatory variables, variable selection was performed using Elastic Net to determine the optimal genetic model for each SNP. It is expected that determining the genetic model prior to creating the learning model according to the present invention will improve the accuracy of determining skin type based on SNPs.
[0045] For the determination of SNPs in the subjects of analysis, saliva was used as the sample. Saliva was collected using Oragene® DNA OG-500 (DNA Genotek Inc.) and the DNA was stabilized. DNA was purified from the saliva, and SNPs were determined using a DNA array to obtain information on the 79 SNPs that were pre-selected.
[0046] Example 4: Creation of a learning model to determine skin type by classifying individuals into high-value and non-high-value groups (or low-value and non-low-value groups) and using the classification results as the target variable. Based on the skin condition measurements selected from a group consisting of wrinkles, blemishes (blemishes 1-3), cheek melanin amount (skin tone 1), brightness (skin tone 2), yellowness (skin tone 3), inner upper arm skin tone (skin tone 4), elasticity, wrinkle area, wrinkle volume, and maximum wrinkle depth, high-value and low-value skin condition groups were determined for each age group based on the distribution of the respective measurements. Specifically, in the high-value group model for determining susceptibility to a skin type (for example, if the target skin type is blemishes, then susceptibility to blemishes), a value of 1 was defined as the case where the skin measurement values obtained from the skin examination were in the top 25% of all data included in each age group (a range of 5-year age increments), and a value of 0 was defined as the case in all other cases (non-high-value group) (Figure 3). Furthermore, in the case of the low-value group model that determines the likelihood of developing a skin condition (for example, if the target skin condition is blemishes, then the likelihood of developing blemishes), a value of 1 was defined as the case where the skin measurement values obtained from the skin test were in the bottom 25% of all data included in each age group (a range of 5-year age increments), and all other cases were defined as 0.
[0047] For the high-value group determination model, the dependent variable was set to 1 for the high-value group and 0 for the non-high-value group. Information on 79 types of SNPs and information on environmental factors based on questionnaire results were input as independent variables, and logistic regression analysis was performed to create a learning model for determining skin constitution. The number of SNPs used in creating the learning model was defined as n. Models were created for n=1~4 (m1) and 5~10 (m2). In the learning model for determining skin constitution, a constant term is determined for each independent variable, and by inputting the independent variables, the likelihood of developing a skin constitution (possibility of belonging to the high-value group of skin condition) and / or the difficulty of developing a skin constitution (possibility of belonging to the low-value group of skin condition), which are the dependent variables, can be output.
[0048] Example 5: Validation of the Learning Model For the created learning model that determines skin type, the likelihood (or unlikelihood) of developing each skin type was input by inputting explanatory variables from the validation data. Based on this and the classification of the validation data's skin condition into high-value (or low-value) groups, an ROC curve was obtained, and the area under the ROC curve (AUC) and sensitivity were calculated (Figure 4). Sensitivity was determined using the optimal cutoff value obtained from the ROC curve (such as the value of the point with the minimum distance from the upper left corner of the ROC curve (the point where both sensitivity and specificity are 1)) or a value set independently of the ROC curve (for example, setting the cutoff value to 0.5 because the skin type score obtained from the prediction model is a probability value). The frequency of SNP occurrences was examined in the learning models that determine the 100 skin types thus created, and the SNPs used in the learning models that determine each skin type (spot 1, spot 2, spot 3, skin color 1, skin color 2, skin color 3, skin color 4, wrinkle, elasticity, wrinkle area, wrinkle volume, maximum wrinkle depth) are shown in the table below. Based on the frequency of SNP occurrence and biochemical findings, SNPs to be used in the learning model were selected, and from the created learning models, the model with the highest AUC while utilizing these SNPs was selected.
[0049] [Table 12]
[0050] Table 13
[0051] Table 14
[0052] Table 15
[0053] Table 16
[0054] Table 17
[0055] Table 18
[0056] Table 19
[0057] Table 20
[0058] Table 21
[0059] Table 22
[0060] Table 23
[0061] The SNPs listed above are each used in aging model equations for various skin conditions. We examined the functional aspects of the genes to which these SNPs belong and identified the genes involved in skin resistance to aging. Then, we investigated and selected the SNPs that influence the function of each gene, and presented them in the table. [Table 24]
[0062] Of the above SNPs, the following SNPs were used in particular to evaluate resistance to aging: [Table 25]
[0063] Example 6: Evaluation of skin's resistance to aging SNP information was obtained from subjects, and scores were calculated for each of the following based on the phenotype and genetic model of each SNP: cell activation, skin shielding, facial shape modeling, metabolic maintenance, skin tone assist, irritation protection, damage control, aquavitamin utilization, and oilvitamin utilization. Specifically, scores were assigned to the phenotype of each SNP according to the table below. The three resistances with the lowest scores were selected as the three resistances for which prevention and resistance enhancement are recommended for subjects. Preventive measures against aging can be proposed for the three resistances with the lowest scores. [Table 26]
[0064] Example 7: Verification of evaluated skin resistance Based on the results of genetic testing, we clarified the strength and balance of nine types of resistance to skin aging and developed an algorithm to propose three types of resistance to skin aging that we recommend customers focus on for prevention and strengthening. We verified the effectiveness of this algorithm based on the genetic testing results, skin measurement results, and skin concern questionnaire results of approximately 1500 subjects. Specifically, for each SNP present in the subjects, we scored their resistance to skin aging according to the definitions in Tables 25 and 26. Furthermore, when the three resistances could not be defined solely from the genetic testing results, we successfully narrowed down the range of resistance to skin aging by using the results of a nine-type skin concern questionnaire created independently by the inventors. As an example, after determining the score for each resistance to aging for all subjects and examining the distribution of these scores, we confirmed that the determination rate for the three types of resistance to skin aging that we recommend customers focus on for prevention and strengthening averaged 83.3%. This demonstrates that the algorithm newly developed by the inventors is suitable as a core technology for our newly developed service, which helps improve the balance of resistance to skin aging according to the customer's personalized skin type and skin concerns.
[0065] Example 8: An example demonstrating the effectiveness of the method for determining the resistance of skin to aging according to the present invention. Table 27 shows the daily intake of water-soluble vitamins A1 and A2 from two women in their 60s who were judged to have low aquavitamin utilization capacity (aquavitamin utilization capacity: 1). Table 28 shows the degree of blemishes in both women. The subject with higher water-soluble vitamin intake had less blemishes. This demonstrates the effectiveness of the method for determining resistance capacity in the present invention and is an example of how the effects of skin aging caused by SNPs can be reduced by living a lifestyle that is in line with one's resistance capacity. [Table 27] [Table 28]
Claims
1. A method for determining skin resistance to aging based on SNPs in genes involved in skin resistance to aging, the following: Cellular homeostasis maintenance ability based on at least one SNP selected from the group consisting of rs1050565, rs2232228, and rs8110862; Barrier function retention force based on at least one SNP selected from the group consisting of rs2227564 and rs8110862; Circulation maintenance force based on at least one SNP selected from the group consisting of rs2010963 and rs833061; Inflammatory modulating capacity based on at least one SNP selected from the group consisting of rs1061622 and rs2227564; Water-soluble vitamin modifiers based on at least one SNP selected from the group consisting of rs1801133 and rs2298585; and Lipid-soluble vitamin regulation capacity based on at least one SNP selected from the group consisting of rs10882272, rs2108622, and rs2282679 The method by which the above is determined.
2. The ability to maintain cellular homeostasis is as follows: The method according to claim 1, determined by at least one SNP selected from the group consisting of rs1050565, rs2232228, and rs8110862.
3. The barrier function retention force is as follows: The method according to claim 1, determined by at least one SNP selected from the group consisting of rs2227564 and rs8110862.
4. The aforementioned circulatory maintenance force is as follows: The method according to claim 1, determined by at least one SNP selected from the group consisting of rs2010963 and rs833061.
5. The aforementioned inflammation-modulating power is as follows: The method according to claim 1, determined by at least one SNP selected from the group consisting of rs1061622 and rs2227564.
6. The aforementioned water-soluble vitamin modifiers are as follows: The method according to claim 1, determined by at least one SNP selected from the group consisting of rs1801133 and rs2298585.
7. The fat-soluble vitamin modulating capacity is as follows: The method according to claim 1, determined by at least one SNP selected from the group consisting of rs10882272, rs2108622, and rs2282679.
8. A method for proposing preventive measures against aging according to the resistance determined by the method according to any one of claims 1 to 7.
9. The method according to claim 8, comprising determining a plurality of resistances selected from the group consisting of the ability to maintain cellular homeostasis, the ability to maintain barrier function, the ability to maintain circulation, the ability to regulate inflammation, the ability to regulate water-soluble vitamins, and the ability to regulate lipid-soluble vitamins, and proposing a corresponding preventive measure for at least one resistance that is determined to be weak.
10. It is the determining mechanism for the skin's resistance to aging. An input section for inputting SNP information about genes involved in resistance to skin aging. Here, the SNP information for the aforementioned gene is rs1050565, rs2232228, rs8110862, rs2227564, rs2010963, rs833061, rs1061622, rs1801133, rs2298585, rs10882272, rs2108622, rs2282679 This is SNP information of an SNP selected from a group consisting of the following: A memory unit that has pre-stored the relationship between SNP information and the skin's resistance to aging. A processing unit compares the SNP information input from the input unit with the relationship between the SNP information stored in the memory unit beforehand and the resistance to skin aging, and determines the resistance to skin aging. Output unit that outputs the determined resistance to skin aging. Includes, Here, the following: Cellular homeostasis maintenance ability based on at least one SNP selected from the group consisting of rs1050565, rs2232228, and rs8110862; Barrier function retention force based on at least one SNP selected from the group consisting of rs2227564 and rs8110862; Circulation maintenance force based on at least one SNP selected from the group consisting of rs2010963 and rs833061; Inflammatory modulating capacity based on at least one SNP selected from the group consisting of rs1061622 and rs2227564; Water-soluble vitamin modifiers based on at least one SNP selected from the group consisting of rs1801133 and rs2298585; and Lipid-soluble vitamin regulation capacity based on at least one SNP selected from the group consisting of rs10882272, rs2108622, and rs2282679 The determination device, which determines the
11. The aforementioned memory unit further stores preventive measures corresponding to the skin's resistance to aging. The processing unit reads from the storage unit the preventive measures corresponding to the resistance force determined in the processing unit, The determination device according to claim 10, wherein the output unit outputs the read-out preventive action.
12. The determination device according to claim 11, wherein the determination device determines a plurality of resistances selected from the group consisting of cell homeostasis maintenance ability, barrier function maintenance ability, circulation maintenance ability, inflammation regulation ability, water-soluble vitamin regulation ability, and fat-soluble vitamin regulation ability, and the output unit of the determination device outputs a corresponding preventive measure for at least one resistance that is determined to be low.
13. A program that causes a computer, including an input unit, a memory unit, a processing unit, and an output unit, to determine the resistance of skin to aging, the following: The processing unit receives a command to determine the resistance to skin aging based on SNP information about genes involved in resistance to skin aging input from the input unit, and the relationship between SNP information previously stored in the memory unit and the resistance to skin aging; A command is output from the output unit to determine the skin's resistance to aging. Includes Here, the SNP information for the aforementioned gene is as follows: rs1050565, rs2232228, rs8110862, rs2227564, rs2010963, rs833061, rs1061622, rs1801133, rs2298585, rs10882272, rs2108622, and rs2282679 This is information about SNPs selected from a group consisting of the following: Here, the following: Cellular homeostasis maintenance ability based on at least one SNP selected from the group consisting of rs1050565, rs2232228, and rs8110862; Barrier function retention force based on at least one SNP selected from the group consisting of rs2227564 and rs8110862; Circulation maintenance force based on at least one SNP selected from the group consisting of rs2010963 and rs833061; Inflammatory modulating capacity based on at least one SNP selected from the group consisting of rs1061622 and rs2227564; Water-soluble vitamin modifiers based on at least one SNP selected from the group consisting of rs1801133 and rs2298585; and Lipid-soluble vitamin regulation capacity based on at least one SNP selected from the group consisting of rs10882272, rs2108622, and rs2282679 The program that determines the above.
14. The program according to claim 13, wherein the resistance to skin aging is at least one selected from the group consisting of the ability to maintain cell homeostasis, the ability to maintain barrier function, the ability to maintain circulation, the ability to regulate inflammation, the ability to regulate water-soluble vitamins, and the ability to regulate fat-soluble vitamins.
15. The aforementioned program is as follows: A command to store in the memory unit a treatment corresponding to the skin's resistance to aging, A command to operate the processing unit to read from the storage unit the action corresponding to the resistance force determined in the processing unit, The output unit is given a command to output the read action. The program according to claim 13 or 14, further comprising:
16. The program provides instructions to determine multiple resistances selected from the group consisting of the ability to maintain cellular homeostasis, the ability to maintain barrier function, the ability to maintain circulation, the ability to regulate inflammation, the ability to regulate water-soluble vitamins, and the ability to regulate fat-soluble vitamins. A command is issued to the output unit to output a corresponding preventive action for at least one resistance level that the processing unit has determined to be low. The program according to claim 15, including the program described in claim 15.