Topical application of a skin serum with Progerin inhibitor helps alleviate human skin aging

Topical application of a skin serum with Progerin inhibitor helps alleviate human skin aging | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Topical application of a skin serum with Progerin inhibitor helps alleviate human skin aging View ORCID Profile So-mi Kang , Minju Kim , Tae-Gyun Woo , Soyoung Park , Bae-Hoon Kim , Bum-Joon Park doi: https://doi.org/10.1101/2025.09.10.25335131 So-mi Kang 1 Department of Molecular Biology, College of Natural Science, Pusan National University , Busan 46241, Republic of Korea Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for So-mi Kang Minju Kim 2 Rare Disease R&D Center , PRG S&T Co., Ltd. , Busan 46274, Republic of Korea Find this author on Google Scholar Find this author on PubMed Search for this author on this site Tae-Gyun Woo 2 Rare Disease R&D Center , PRG S&T Co., Ltd. , Busan 46274, Republic of Korea Find this author on Google Scholar Find this author on PubMed Search for this author on this site Soyoung Park 2 Rare Disease R&D Center , PRG S&T Co., Ltd. , Busan 46274, Republic of Korea Find this author on Google Scholar Find this author on PubMed Search for this author on this site Bae-Hoon Kim 2 Rare Disease R&D Center , PRG S&T Co., Ltd. , Busan 46274, Republic of Korea Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: bjpark1219{at}pusan.ac.kr bk728{at}prgst.com Bum-Joon Park 1 Department of Molecular Biology, College of Natural Science, Pusan National University , Busan 46241, Republic of Korea 2 Rare Disease R&D Center , PRG S&T Co., Ltd. , Busan 46274, Republic of Korea Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: bjpark1219{at}pusan.ac.kr bk728{at}prgst.com Abstract Full Text Info/History Metrics Supplementary material Data/Code Preview PDF ABSTRACT Skin aging is a complex process driven by intrinsic and extrinsic factors, resulting in structural and functional changes such as reduced elasticity, hydration loss, and the appearance of wrinkles. This study evaluates the efficacy and safety of a topical formulation with common skincare ingredients and a Progerin inhibitor, which is designed to combat multiple signs of skin aging. A 4-week clinical trial was conducted with 21 female participants aged 30–50. The study measured key parameters of skin health, including crow’s feet wrinkle reduction, facial lifting improvement, skin hydration, elasticity, density, and tone brightness. Objective assessments, including dermatological evaluations and quantitative measurements, were complemented by subjective feedback from participants through efficacy and preference surveys. The results demonstrated significant improvements across all evaluated parameters. After 4 weeks of use, participants exhibited a 5.631% reduction in wrinkles, a 3.234% improvement in facial lifting, an 18.435% increase in skin hydration, an 8.563% enhancement in elasticity, a 3.424% improvement in skin tone brightness, and a 23.583% increase in skin density (p < 0.05). No adverse reactions were reported, and the product was well-tolerated. Participant surveys further confirmed high levels of satisfaction with the skin serum’s performance and usability. These findings indicate that the progerin inhibitor effectively improves multiple signs of skin aging, especially skin density increase, and supports its potential as a comprehensive anti-skin aging ingredient. This study contributes to advancing topical skincare formulations aimed at rejuvenating and maintaining healthy, youthful skin. Research Objective This study aimed to evaluate the effects of a skin serum containing a 1 % progerin inhibitor on eye wrinkles, facial lifting, skin moisturizing, skin elasticity, skin density, and skin tone brightness in women aged 30 to 55. The test was conducted by measuring the relevant test items before product use, and at 2 weeks and 4 weeks after use. After the trial was completed, effectiveness and preference surveys were conducted. INTRODUCTION The skin, as the largest organ of the body, plays a critical role in protecting internal tissues while serving as a visible indicator of health and age [ 1 ]. Aging induces a variety of changes in the structure and function of the skin, impacting its appearance, resilience, and overall health [ 2 ]. These changes are influenced by intrinsic aging, which is genetically determined, and extrinsic aging, which results from environmental factors like sun exposure, pollution, and lifestyle choices [ 3 – 5 ]. With age, the epidermis, the outermost layer of the skin, has diminished skin density, leading to a more fragile barrier [ 2 , 6 ]. The dermis, which houses collagen, elastin, and glycosaminoglycans, also undergoes significant changes. Collagen production decreases, and existing collagen fibers degrade, resulting in reduced firmness and elasticity [ 7 ]. Elastin, essential for the skin’s ability to return to its original shape, also diminishes and becomes fragmented, contributing to sagging. Hyaluronic acid, which retains moisture, declines, leading to dryness and a lack of plumpness [ 8 – 10 ]. Aging skin exhibits a slower turnover of cells, which impairs wound healing and reduces the efficiency of the skin’s natural barrier [ 2 , 7 , 11 ]. Sebum production decreases, particularly in postmenopausal women, exacerbating dryness [ 12 ]. Furthermore, blood flow in the skin diminishes, reducing oxygen and nutrient delivery, and giving the skin a dull, sallow appearance [ 2 , 13 ]. The quest for effective anti-skin aging solutions has gained significant attention in dermatological research and the cosmetic industry [ 14 ]. Among various approaches, topical formulations are particularly valued for their non-invasive application and ability to target specific signs of aging [ 15 ]. These formulations often combine active ingredients designed to enhance hydration, improve elasticity, and stimulate cellular repair mechanisms to rejuvenate the skin [ 16 ]. Progerin is a mutated form of the lamin A protein, encoded by the human LMNA gene, and is primarily associated with Hutchinson-Gilford Progeria Syndrome (HGPS) and Werner syndrome (WS), rare genetic conditions that cause accelerated aging [ 17 – 22 ]. Progerin has been observed to accumulate in normal aging skin, though in smaller quantities, and plays a crucial role in age-related changes in skin structure and function. Its connection to cellular homeostasis and its contribution to premature aging in most cell types has been extensively discussed. Several studies have explored progerin as a biomarker of aging, suggesting it could be one of the few known biological indicators that trigger the aging process at a specific stage [ 23 – 26 ]. Fibroblasts from older individuals have shown numerous abnormal nuclei that strongly reacted with progerin-specific antibodies after extended culture [ 20 , 27 ], demonstrating that progerin can be expressed in normal cells. To further understand the link between progerin expression and aging in humans, Djabali et al. analyzed skin biopsies from 150 healthy individuals. Their findings revealed that similar splicing events occur in vivo at low levels across all age groups [ 28 ]. While progerin mRNA expression level is generally low, it accumulates over time in a subset of skin fibroblasts and fully differentiated keratinocytes [ 28 , 29 ], highlighting the potential of progerin research to enhance our understanding of physiological aging. We have developed therapeutic approaches specifically targeting progerin by utilizing an inhibitor drug designed to promote its degradation. When administered orally, this inhibitor alleviates skin thinning in an HGPS mouse model. It improves senescence-related phenotypes in cell lines derived from WS patients [ 19 – 22 , 30 ]. To assess its safety in humans, randomized, double-blind, placebo-controlled, single ascending dose trials, including studies on food interactions, were performed. These were followed by multiple ascending dose studies aimed at evaluating the inhibitor’s safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy participants ( NCT04512963 ). Across all tested dose levels, up to a maximum of 2400 mg, the inhibitor demonstrated an excellent safety profile [ 19 ]. In this study, we investigate the efficacy of a novel topical formulation designed to function as an anti-skin aging reagent. To test the effects on multiple aging-related concerns, we formulated a skin serum containing a progerin inhibitor together with skin-nourishing compounds. By leveraging a multifaceted approach to skin health, the product aims to offer comprehensive anti-skin aging benefits. This paper presents a detailed analysis of the skin serum’s efficacy and safety through a 4-week clinical trial involving female participants aged 30 - 50. Measurements include objective assessments of wrinkle reduction, skin lifting, hydration, elasticity, density, and brightness, as well as subjective evaluations through participant surveys. The findings offer valuable insights into the potential of the progerin inhibitor as an effective ingredient for mitigating the signs of aging and enhancing skin rejuvenation. MATERIALS AND METHODS Test Product: The general information of the test product is shown in Table 1 . Distribution of Test Product: The test product was provided by the sponsor, PRGS & Tech Co., Ltd., and was used by the test subjects with labels attached, which specified the test number, subject number, product name, manufacturer, storage method, etc. Usage Instructions for the test product: After cleansing, take an appropriate amount on the fingertips and gently apply it to the required areas, tapping gently to help absorption. Additionally, during the human application test period, the use of any cosmetics containing active ingredients that could affect the test results (e.g., functional cosmetics for whitening, wrinkle improvement, etc.) other than the test product provided by this center was strictly prohibited. The frequency of use of test product was 4 weeks (once a day in the evening). The test product was stored in a sealed condition at room temperature. Ingredients of the skin serum: The information on the ingredients is shown in Table 2 . Selection Criteria of Test Subjects: The following criteria were established for participant selection in the clinical trial evaluating the efficacy of the skin serum: Adult women aged 30 to 50 years who exhibit visible eye wrinkles were considered suitable candidates for the study. Participants were required to be fully informed about the trial details by the principal investigator or an authorized delegate. They had to voluntarily agree to participate by signing a written informed consent form. Only healthy individuals without any infectious skin diseases or acute or chronic physical conditions were included in the trial to ensure unbiased results and participant safety. Participants needed to be available for follow-up visits and assessments throughout the trial period to facilitate accurate data collection and evaluation of results. These criteria were carefully designed to ensure the selection of an appropriate study population and to maintain the validity and reliability of the clinical trial outcomes. Exclusion Criteria of Test Subjects: Participants who met any of the following criteria were excluded from the clinical trial to ensure the safety and reliability of the study: Women who were pregnant, breastfeeding, or had the potential to become pregnant during the trial were excluded to avoid risks to both the participant and a potential fetus. Individuals who declined to participate or did not provide signed informed consent were not eligible. Participants with psychiatric disorders that could affect compliance or understanding of the trial procedures were excluded. Individuals who had undergone immunosuppressive therapy within 3 months prior to the trial were excluded. Individuals who had received systemic steroids or phototherapy within 1 month prior to the trial were excluded. Those with lesions in the test area that could interfere with accurate measurement were excluded. Individuals with atopic skin or severe reactions or allergies to cosmetics, medications, or sun exposure were excluded. Participants who had undergone skin peeling or cosmetic treatments within 3 months prior to the trial were excluded to avoid confounding effects. If the principal investigator or the responsible person deemed participation unfeasible due to the above factors or other considerations, the individual was excluded. These exclusion criteria were meticulously designed to minimize risks, ensure participant safety, and maintain the integrity of the study results. Criteria for Discontinuation and Withdrawal: Test subjects who initially agreed to participate in the trial but meet any of the following criteria will be withdrawn from the human application test: 1) If the test subject expresses a refusal to continue participation. 2) If the test subject experiences a serious adverse reaction or develops abnormal reactions, such as erythema, at the test site, and requests to stop the trial. 3) If the test product causes hypersensitivity reactions. 4) If use is discontinued due to other health conditions. 5) If there are any other unavoidable circumstances. 6) If the test subject does not comply with the prescribed trial procedures. 7) If the test subject fails to be followed up during the observation period Number of Test Subjects: A total of 23 individuals were selected for the initial screening for this human application test, and all of them met the selection criteria and participated in the trial. Out of the 23, 2 individuals withdrew midway, so 21 individuals completed the trial. Test Subject Visit Schedule: Visit 1 (Screening, Test Subject Selection, and Skin Measurements): After explaining the study, test subjects who agreed to participate and signed the consent form underwent demographic surveys, screening for inclusion/exclusion criteria, and medical history investigations. The method for using the test product was explained, and the test product was then applied. Before using the test product, measurements were taken for eye wrinkles, facial lifting, skin moisturizing, skin elasticity, skin density, and skin tone (brightness). Visit 2 (Skin Measurements): After Visit 1, any adverse reactions and concurrent treatments were investigated. Two weeks after using the test product, measurements were taken again for eye wrinkles, facial lifting, skin moisturizing, skin elasticity, skin density, and skin tone (brightness), along with an evaluation of skin conditions. Visit 3 (Skin Measurements and Questionnaire): After Visit 2, any adverse reactions and concurrent treatments were again reviewed. Four weeks after using the test product, measurements were taken for eye wrinkles, facial lifting, skin moisturizing, skin elasticity, skin density, and skin tone (brightness), along with an evaluation of skin conditions. After the trial was completed, effectiveness and preference surveys were conducted. Evaluation Areas and Measurement Methods: For device-based evaluations, the test subjects were allowed to rest in a controlled environment (temperature: 20–25°C, humidity: 40–60%) for 30 minutes to allow the skin surface temperature and humidity to adapt to the environment. During this resting period, water intake was restricted. An investigator conducted the objective measurements, and the same area was measured for each test. 1) Eye Wrinkle Measurement: Eye wrinkles were measured using the 3D skin imaging device, Antera 3D CS (Miravex Ltd., Ireland). The same area around the eyes was photographed before and after using the test product. Specific regions of the eye wrinkle area were selected from the stored images, and the Indentation Index (A.U.) value within the specified area was analyzed. A decrease in the Indentation Index indicates an improvement in skin wrinkles. 2) Facial Lifting Measurement: Facial lifting was measured using the F-ray device (BEYOUNG Ltd., Korea), which creates a contour map of the skin. The images captured by the device were analyzed using Image-ProⓇ Plus (Media Cybernetics, USA). The measurements were taken on the same cheek area before and after using the test product, and the analysis was based on the curves formed near the test area. 3) Facial (cheek) lifting measurement: A circle formed near the cheekbone was used as the reference. A straight line was drawn from the center of the circle to the corner of the mouth, and the angle between this line and a horizontal line was measured ( Figure 1 ). A smaller angle between the two lines indicates a lifting effect. 4) Skin Moisturizing Measurement: Skin moisturizing was evaluated using the Corneometer CM825 (Courage+Khazaka Electronic GmbH, Germany). The same right cheek area was measured before and after using the test product. During measurement, the Corneometer probe was placed in contact with the skin, and the test was performed three times using the sensor. The average value of these measurements was used as the hydration assessment data. The Corneometer operates on the principle that skin, as a basic insulator, allows electricity to pass more easily when it contains more moisture. It measures the capacitance at the contact point of the probe. Thus, the moisture content and capacitance are directly proportional, meaning that a higher measurement value indicates a higher moisture content. The unit of measurement is an arbitrary unit (A.U.), which is a unit constant. 5) Skin Elasticity Measurement: Skin elasticity was measured using the Cutometer MPA580 (Courage-Khazaka Electronic GmbH, Germany). The same right cheek area was measured before and after using the test product, and the R2 (recovery force) value was used as the skin elasticity evaluation data. The R2 value represents overall elasticity, and the closer the value is to 1, the more elastic the skin is. 6) Skin Density Measurement: Skin density was measured using an ultrasound imaging device, the Skin Scanner DUB-USB (TPM Taberna Pro Medicum, Germany). The same left eye area was imaged before and after using the test product. The unit of measurement was density (%). An increase in the value indicates an improvement in skin density. 7) Skin Tone (Brightness) Measurement: Skin tone brightness was measured using the VISIA CR (Canfield Imaging Systems, USA) before and after using the test product. The same facial area of the test subject was imaged. The captured images were analyzed using Image-ProⓇ Plus. A specific area in the image was selected, and the RGB values of that area were obtained and then converted to CIELab values. The L* value (lightness), which indicates skin brightness, was used to assess skin tone. A higher L* value indicates an improvement in brightness. 8) Efficacy Questionnaire (Global Assessment of Efficacy): After using the test product, test subjects were asked to respond to a questionnaire regarding the measurement items using a 5-point scale: Very Good (4), Good (3), Average (2), Poor (1), Very Poor (0). The researcher calculated the percentage of test subjects for each response and assessed the efficacy of the test product based on these results. 9) Product Preference Questionnaire: After using the test product, test subjects were asked to fill out a questionnaire about their experience with the product. The evaluation criteria included skin moisture, smoothness, spreadability, absorbency, fragrance, and overall feel. The subjects rated each item using a 5-point scale: Very Good (4), Good (3), Average (2), Poor (1), Very Poor (0). 10) Safety Evaluation: The safety of the test product was assessed by reviewing all reported adverse reactions during the trial period for all test subjects who used the product. The incidence rate of adverse reactions was calculated and used as safety evaluation data for the product. 11) Adverse Reaction Evaluation: Any abnormal skin symptoms that occurred during the use of the test product were monitored through a questionnaire throughout the trial period to assess the occurrence and severity of the symptoms. Test subjects were instructed to immediately report any unusual symptoms to the study coordinator. If adverse reactions were reported, the study coordinator informed the principal investigator. The principal investigator then assessed the severity of the symptoms, determined the potential association with the test product, and decided on appropriate actions, including whether the subject could continue participating in the trial. Evaluation Criteria: 1) Primary Efficacy Evaluation Variables: The primary efficacy evaluation variables for the test product were based on the measurements taken before and after the use of the test product, including eye wrinkles, facial lifting, skin moisturizing, skin elasticity, skin density, and skin tone brightness. 2) Secondary Efficacy Evaluation Variables: The secondary efficacy evaluation variables for the test product were based on the results of the efficacy assessment questionnaire regarding skin improvement after using the test product. Statistical Analysis: To determine the significance of the changes in measurements before and after using the test product, statistical analysis was performed using SPSS 19.0 software. Statistical significance was determined at a 95% confidence interval with a p-value < 0.05. The p-values were rounded to three decimal places. Continuous variables were summarized as means and standard deviations, while categorical variables were summarized as frequencies and percentages. For data with three or more repeated measurements, normality tests were performed, and parametric methods such as repeated measures ANOVA were used, followed by post-hoc tests using the Bonferroni method. For non-parametric methods, the Friedman test was used, and paired comparisons were performed using the Wilcoxon signed-rank test, with post-hoc significance adjustments using the Bonferroni method. Safety Protection of Test Subjects: This human application test was conducted in accordance with the Declaration of Helsinki, respecting human dignity and rights, and ensuring that no harm or disadvantage would come to the test subjects. The study coordinator confirmed the health status of each test subject before enrollment to ensure they were fit to participate in the study. The study coordinator was thoroughly familiar with the test product and made every effort to ensure the safety of the test subjects. Informed Consent and Consent Explanation: Before the study began, the study principal investigator and the study coordinator provided detailed explanations of the study, including the inclusion and exclusion criteria, to test subjects who met all the requirements. Test subjects (or their guardians) were given ample opportunity to understand all aspects of the study and any potential outcomes. The information provided to the test subjects was documented, and the study principal investigator confirmed their consent by signing the informed consent form. Confidentiality: The names of all test subjects involved in the study were kept confidential. The signed informed consent forms were stored by the researchers, and the study coordinator or monitor managed a separate list containing the test subject numbers, initials, and names, which was used for future records and evaluation. Other Protective Measures for Test Subjects: The PNK Skin Clinical Research Center had the necessary facilities and expert personnel in place to ensure the proper conduct of the study, as outlined in the study protocol, and to prioritize the safety of the test subjects. Researchers were informed in advance about the potential adverse reactions and precautions stated in the study protocol, and any adverse events occurring during the study were addressed appropriately and reported to the sponsor. In the case of any direct or indirect harm resulting from participation in this human application test, the study principal investigator or the study coordinator would take all necessary actions to treat the injury. If any adverse reactions or damage occurred as a result of the test product or during the treatment of adverse reactions, the sponsor (PRGS & Tech Co., Ltd.) would provide compensation for the damage caused directly by the test product. However, hospitalization fees, examination costs, and consultation fees unrelated to the study would be the responsibility of the test subject. RESULTS Participant Information The average age of the 21 participants who completed the test, excluding 2 dropouts, was 43.3 years. The participants consisted of 4 individuals in their 30s, 16 in their 40s, and 1 in their 50s, with all participants being female ( Table 3 ). Out of 23 participants who initially joined the test, 2 dropped out, leaving a total of 21 participants who completed the test ( Table 4 ). Among the 21 participants who completed the test, 6 had dry skin, 12 had moderately dry skin, and 3 had normal skin ( Table 5 ). In the survey regarding skin conditions, including skin diseases, itching, stinging, erythema, cosmetic side effects, drug side effects, photosensitivity, and atopic disease history, none of the participants reported any relevant experiences. Additionally, no participants reported experiences in other categories ( Table 6 ). Compliance with product ( Table 1 and Table 2 ) usage was calculated as the percentage of the number of times the product was used compared to the required usage during the test period. The overall compliance rate of the 21 participants who completed the test was 99.320%, with the highest compliance at 100.000% and the lowest at 89.286%. Since no participants showed a compliance rate below 80%, the data from all participants were included in the analysis ( Table 7 ). Download figure Open in new tab Figure 1. F-ray facial lifting angle analysis image. A smaller angle between the two lines indicates a lifting effect. Primary Efficacy Evaluation The results of measuring changes in crow’s feet wrinkles after using the test showed a reduction of 2.628% after 2 weeks and 5.631% after 4 weeks compared to before use (p < 0.05) ( Table 8 ). To examine changes in facial lifting caused by the test product, changes in the cheek area angle were analyzed ( Figure 1 ). Compared to before using the product, there was a reduction of 1.515% after 2 weeks and 3.234% after 4 weeks (p < 0.05) ( Table 9 ). The results of measuring changes in skin moisture after using the test product showed a significant increase of 10.448% after 2 weeks and 18.435% after 4 weeks compared to before use (p < 0.05) ( Table 10 ). The results of measuring changes in skin elasticity after using the test product showed a significant increase of 4.500% after 2 weeks and 8.563% after 4 weeks compared to before use (p < 0.05) ( Table 11 ). The results of measuring changes in dermal density after using the test product showed a significant increase of 10.543% after 2 weeks and 23.583% after 4 weeks compared to before use (p < 0.025) ( Table 12 ). Ultrasonography images showing changes in the dermal density of subjects. The density of the dermal cells gradually increased after use of the product ( Figure 2 ). The results of measuring changes in skin tone brightness after using the test product showed an increase of 1.951% after 2 weeks and 3.424% after 4 weeks compared to before use (p < 0.05) ( Table 13 ). Download figure Open in new tab Figure 2. Ultrasonography images showing changes in dermal density. The density of dermal cells (green dots) increased in the combinatorial group after observation for 2 or 4 weeks. The results from three participants (S14, 18, 20) were displayed as representative images. Secondary Efficacy Evaluation A survey was conducted to evaluate the effects of the test product on crow’s feet wrinkle improvement, facial lifting improvement, skin moisture improvement, skin elasticity improvement, skin density improvement, and skin tone brightness improvement. The survey results included the calculation of averages, standard deviations, and the percentage of participants for each response ( Table 14 ). The survey results showed that 100.000% of the participants rated crow’s feet wrinkle improvement and facial lifting improvement as average or better. Additionally, 95.238% of the participants rated skin moisture improvement, skin elasticity improvement, and skin density improvement as average or better, while 90.476% rated skin tone brightness improvement as average or better. A survey was conducted to assess participants’ preferences regarding skin hydration, smoothness, spread-ability, absorbency, fragrance, and overall usability of the product after use. The results were expressed as averages, standard deviations, and the percentage of responses from participants ( Table 15 ). The survey results showed that 100.000% of the participants rated smoothness, spread-ability, absorbency, and overall usability as average or better. Additionally, 95.238% of the participants rated skin hydration and fragrance as average or better. Safety Evaluation The safety of the test product was assessed by the researcher based on a combination of visual evaluations of the application site and participant survey results ( Table 16 and Table 17 ). During the period in which participants used the test product, no reports of specific adverse skin reactions were made. Additionally, no abnormal findings were observed in physical examinations conducted by a dermatologist. The safety survey conducted with participants revealed that no specific symptoms related to adverse skin reactions were observed. DISCUSSION This study evaluated the effects of using the skin serum for 4 weeks in women aged 30–50, measuring its impact on crow’s feet wrinkles, facial lifting, skin moisture, skin elasticity, skin density, and skin tone brightness. Efficacy and preference surveys were completed after the study. Among the 21 participants who completed the study (excluding 2 dropouts), all were women with an average age of 43.381 years. The selected participants had no specific skin conditions, diseases, or medication histories that could affect the study. After using the product, crow’s feet wrinkles showed a significant reduction after 2 weeks and 4 weeks compared to before use (p < 0.05). Changes in facial lifting, assessed through cheek angle measurements, showed a significant reduction after 2 weeks and 4 weeks compared to before use (p < 0.05). Skin moisture, Skin elasticity, and Skin tone brightness also showed a significant increase after 2 weeks and 4 weeks of product use compared to before use (p < 0.05). Notably, after using the product, skin density showed a significant increase of 10.543% after 2 weeks and 23.583% after 4 weeks compared to before use (p < 0.025). The efficacy evaluation survey results indicated that all participants rated crow’s feet wrinkle improvement and facial lifting improvement as average or better. For skin moisture improvement, skin elasticity improvement, and skin density improvement, 95.238% of participants rated them as average or better, while 90.476% rated skin tone brightness improvement as average or better. During the test period, no specific reports of adverse skin reactions were made, and no abnormal findings were observed during dermatological physical examinations. The skin serum in this report contains sodium hyaluronate, collagen, adenosine, niacinamide, and magnesium ascorbyl phosphate as common skin-nourishing compounds ( Table 2 ). Sodium Hyaluronate is a form of hyaluronic acid and it is known for its exceptional ability to retain moisture, leading to plumper and more hydrated skin, which can reduce the appearance of wrinkles. Collagen as a primary structural protein in the skin, topical collagen can help improve skin elasticity and firmness, although its large molecule size may limit absorption. Adenosine is recognized for its anti-wrinkle properties and it can help improve skin smoothness by energizing the skin’s surface cells and promoting collagen production. Niacinamide is a form of vitamin B3 and it is praised for its ability to improve skin tone, reduce fine lines, and enhance the skin’s barrier function. Magnesium Ascorbyl Phosphate is a stable derivative of vitamin C and it offers antioxidant benefits, promotes collagen synthesis, and can brighten the skin [ 31 – 33 ]. Dermal density reflects the balance and health of the cells in the dermis and the extracellular matrix (ECM), such as collagen, elastin, and hyaluronic acid [ 34 , 35 ]. Fibroblasts are the key contributors, supported by the activities of keratinocytes, endothelial cells, immune cells, and adipocytes [ 36 ]. The degradation or reduced activity of these cells due to intrinsic aging or environmental factors directly impacts dermal density, leading to visible signs of aging such as thinning, sagging, and reduced elasticity of the skin [ 37 ]. Monitoring dermal density is particularly significant as it serves as an indicator of the skin’s regenerative processes, especially following rejuvenating procedures or treatments aimed at improving skin texture and appearance. Improvement in dermal density is often used as an indicator of the enhancement in extracellular matrix (ECM) components such as collagen and elastin, which contribute to skin structure and elasticity. A substantial enhancement in ECM components can be associated with dermal density improvements of 10-20% or more, depending on the context of the treatment or intervention [ 38 – 41 ]. Such results are significant as they often correlate with visible improvements in skin texture, thickness, and resilience. Achieving this percentage of increase reflects the serum’s efficacy in promoting skin regeneration and combating age-related or environmental degradation. These benchmarks are consistent with findings from other dermatological research and are widely recognized as indicators of an effective skin care product. Therefore, if the skin serum with common skin-nourishing compounds and progerin inhibitor increases the dermal density by over 23% in 4 weeks, it indicates that Progerin inhibitor could be used as an excellent supplemental ingredient supporting dermal cells under the skin. This also may imply that Progerin is naturally produced in skin fibroblast of women aged 30 - 50 and successfully cleared by the Progerin inhibitor contained in the skin serum. Progerin is produced due to the alternative splicing of the LMNA gene, which results in a defective form of lamin A protein. In natural aging, progerin accumulates gradually in cells, especially in fibroblasts and keratinocytes in the skin. This accumulation is linked to persistent cellular stress, DNA damage, and impaired repair mechanisms as the body ages. Chronic exposure to environmental factors (e.g., UV radiation, pollution) accelerates progerin accumulation. Ultraviolet (UV) radiation causes direct damage to DNA, including cyclobutane pyrimidine dimers and oxidative damage. Progerin expression upon UV exposure has significant implications for skin health and aging [ 42 ]. UV radiation, particularly UVB (290–320 nm) and UVA (320–400 nm), is a key environmental factor that accelerates skin aging, commonly referred to as photoaging. Research indicates that UV exposure can induce progerin expression in skin cells, which contributes to aging-related structural and functional changes [ 43 , 44 ]. This suggests that the progerin inhibitor might emerge as a promising candidate for inclusion in cream formulations due to its potential to counteract UV-induced skin damage and mitigate harmful effects of progerin on cellular structures. This study demonstrates the efficacy of a skin serum containing common skin-nourishing compounds and the progerin inhibitor in improving various skin aging-related parameters, including dermal density, crow’s feet wrinkles, facial lifting, skin moisture, elasticity, and tone brightness. The serum’s ability to achieve a significant dermal density increase of over 23% within 4 weeks suggests that the progerin inhibitor plays a pivotal role in enhancing skin cell regeneration and combating signs of aging. CONCLUSION In the present study, integrating the progerin inhibitor into skincare formulations represents an innovative approach to addressing aging at the cellular level. The results highlight its potential as a supplemental ingredient for improving skin resilience, promoting regeneration, and protecting against UV-induced damage. 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Share Topical application of a skin serum with Progerin inhibitor helps alleviate human skin aging So-mi Kang , Minju Kim , Tae-Gyun Woo , Soyoung Park , Bae-Hoon Kim , Bum-Joon Park medRxiv 2025.09.10.25335131; doi: https://doi.org/10.1101/2025.09.10.25335131 Share This Article: Copy Citation Tools Topical application of a skin serum with Progerin inhibitor helps alleviate human skin aging So-mi Kang , Minju Kim , Tae-Gyun Woo , Soyoung Park , Bae-Hoon Kim , Bum-Joon Park medRxiv 2025.09.10.25335131; doi: https://doi.org/10.1101/2025.09.10.25335131 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Dermatology Subject Areas All Articles Addiction Medicine (568) Allergy and Immunology (863) Anesthesia (299) Cardiovascular Medicine (4425) Dentistry and Oral Medicine (443) Dermatology (382) Emergency Medicine (607) Endocrinology (including Diabetes Mellitus and Metabolic Disease) (1507) Epidemiology (15221) Forensic Medicine (30) Gastroenterology (1123) Genetic and Genomic Medicine (6588) Geriatric Medicine (667) Health Economics (997) Health Informatics (4524) Health Policy (1368) Health Systems and Quality Improvement (1612) Hematology (540) HIV/AIDS (1264) Infectious Diseases (except HIV/AIDS) (15910) Intensive Care and Critical Care Medicine (1103) Medical Education (623) Medical Ethics (145) Nephrology (667) Neurology (6588) Nursing (346) Nutrition (998) Obstetrics and Gynecology (1143) Occupational and Environmental Health (956) Oncology (3331) Ophthalmology (970) Orthopedics (369) Otolaryngology (420) Pain Medicine (435) Palliative Medicine (129) Pathology (663) Pediatrics (1690) Pharmacology and Therapeutics (691) Primary Care Research (710) Psychiatry and Clinical Psychology (5440) Public and Global Health (9219) Radiology and Imaging (2195) Rehabilitation Medicine and Physical Therapy (1369) Respiratory Medicine (1196) Rheumatology (593) Sexual and Reproductive Health (710) Sports Medicine (529) Surgery (710) Toxicology (99) Transplantation (289) Urology (265) (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'9ffcc3321ac70704',t:'MTc3OTQ2Mjc4MQ=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();