Loss Of Collagen Research Articles

Interstitial Collagen Loss, Myocardial Remodeling, and Function in Primary Mitral Regurgitation

Interstitial collagen loss and cardiomyocyte ultrastructural damage accounts for left ventricular (LV) sphericity and decrease in LV twist and circumferential strain. Normal LV diastolic function belies significantly abnormal left atrial (LA) function and early LV diastolic untwist rate. This underscores the complex interplay of LV and LA myocardial remodeling and function in the pathophysiology of primary mitral regurgitation. In this study, we connect LA function with LV systolic and diastolic myocardial remodeling and function using cardiac magnetic resonance tissue tagging in primary mitral regurgitation.

Gastrocnemius Muscle Injury Is the Condition to Induce Cartilage Degeneration of the Rabbit Tibiofemoral Joint: A New Perspective.

The knee osteoarthritis is a common joint disease that causes pain and inconvenience. Clinically, patients with knee osteoarthritis often have response points on the gastrocnemius. Gastrocnemius plays an essential role in stabilizing joints and changing gait and pace, which also has a close relationship with the knee joint. The objective of this study is to determine changes in the tibiofemoral joint after medial and lateral gastrocnemius injury. Rabbits were divided into a medial gastrocnemius injury group, a lateral gastrocnemius injury group, and a control group with two intervals: 6 and 8 weeks after modeling of the semisevered gastrocnemius. The gastrocnemius was weighed and sectioned for histology. The joint space and subchondral bone were observed using X-ray and microcomputed tomography. The cartilage was observed histologically using Safranin O fast green and Masson and immunohistochemically using antibodies to collagen type II, matrix metalloproteinase 13, and integrin beta1. Results showed muscle fiber atrophy, and fibrotic changes occurred after gastrocnemius semidissociation. After gastrocnemius injury, the femoral condyle of the tibiofemoral joint produced abnormal sclerosis and bone degeneration. The pathological changes of cartilage included disordered or reduced cell alignment, cartilage matrix loss, and collagen loss due to decreased collagen type II and increased matrix metalloproteinase 13 activity. The increase of integrin beta1 in the injured group may be related to mechanical conduction process. The results suggest that gastrocnemius injury is an essential factor in tibiofemoral arthritis.

32659 Clinical assessment of a lip care product for evaluating performance and increasing attribute expectations in the mask wearing era

Well-defined fuller lips, associated with attractiveness/youthfulness, continue to be a desirable trait. Age-related changes to lips include roughness, lip lines and wrinkles, loss of plumpness, hydration, volume, collagen, and elastin. Invasive procedures have disadvantages: risk of complications, affordability, and recovery time, it is the noninvasive treatment methods which are popular with the masses. With new ingredients, there is an ever-expanding list of lip products being introduced to improve/enhance beauty, while remaining inexpensive and most popular fashion trend amongst cosmetics.

Clitorea ternatea flower extract induces platelet-derived growth factor(PDGF) and GPx gene overexpression in ultraviolet (UV) B irradiationinduced collagen loss.

Aim To determine the effect of Clitorea ternatea flower extract (CTFE) in the gel dosage form on the expression of GPx and platelet-derived growth factor (PDGF) in ultraviolet (UV) - B irradiation-induced collagen loss rat model. Methods This is experimental research with post-test control group design. Twenty healthy male Wistar rats were divided into four treatment groups: a sham group, UVB control group, two treatment groups with gel of CTFE 5% and gel of CTFE 10%, respectively. Each group was treated with UVB at 302 nm with a MED of 160 mJ/cm2 for 5 days, whereas the sham group did not receive UVB. In the treatment groups CTFE 5% and CTFE 10% gel were given on the 6th to the 14th day. On day 14 all treatment groups were terminated, and GPx and PDGF gene expression were analysed using qRT-PCR. Results In the group of gel of CTFE 10%, there was a significant increase in GPx gene expression (9.51±1.83) and PDGF (4.36±1.18) compared to the UVB control group which had GPx and PDGF gene expression of 4.90±1.64) and 0.032±0.01, respectively. Conclusion The administration of CTFE gel showed an increase of the expression of GPx and PDGF g.

Investigation of the protective effects of intraperitoneal melatonin in rats receiving laryngeal radiotherapy

ObjectivesTo examine the protective effects of melatonin on laryngeal radiation damage. Materials and methods31 rats were divided into 4 groups as follows: 1) the control (C) group (n=7), was only injected with intraperitoneal ethanol solution; 2) the melatonin (M) group (n=8), was injected intraperitoneal melatonin solution with 5 mg/kg; 3) the radiotherapy (RT) group (n=8) was given laryngeal radiation after intraperitoneal injection of ethanol solution; 4) the M + RT group (n=8), RT was given 30 minutes after 5 mg/kg dose of melatonin solution was injected. Drug and radiation applications were continued for 5 days. The weight changes of the rats were recorded. At the end of the study, inflammation, neutrophil migration and lymphoid aggregates, collagen distribution, laryngeal glandular structures and biochemical analysis of laryngeal tissues [malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant status (TAS)] were determined. ResultsIn the M+RT group, the first day and the 30th weight differences were significantly increased when compared with the RT group (p=0.050). Inflammation, neutrophil migration, lymphoid aggregate, disorganized collagen distribution and loss of glandular tissues were found statistically more in the RT group than in the C group (p<0.05). MDA and TOS levels were in the M + RT group exhibited better values than they did in the RT group (p<0.05). TAS levels was markedly increased in the M + RT group than in the RT group (p<0.001). ConclusionAdministration of melatonin to rats prior receiving laryngeal radiation, decreases the level of oxidative stress markers and increases the level of anti-oxidative markers.

Detergent-Free Decellularization of Notochordal Cell-Derived Matrix Yields a Regenerative, Injectable, and Swellable Biomaterial

Porcine notochordal cell-derived matrix (NCM) has anti-inflammatory and regenerative effects on degenerated intervertebral discs. For its clinical use, safety must be assured. The porcine DNA is concerning because of (1) the transmission of endogenous retroviruses and (2) the inflammatory potential of cell-free DNA. Here, we present a simple, detergent-free protocol: tissue lyophilization lyses cells, and matrix integrity is preserved by limiting swelling during decellularization. DNA is digested quickly by a high nuclease concentration, followed by a short washout. Ninety-four percent of DNA was removed, and there was no loss of glycosaminoglycans or collagen. Forty-three percent of the total proteins remained in the decellularized NCM (dNCM). dNCM stimulated as much GAG production as NCM in nucleus pulposus cells but lost some anti-inflammatory effects. Reconstituted pulverized dNCM yielded a soft, shear-thinning biomaterial with a swelling ratio of 350% that also acted as an injectable cell carrier (cell viability >70%). dNCM can therefore be used as the basis for future biomaterials aimed at disc regeneration on a biological level and may restore joint mechanics by creating swelling pressure within the intervertebral disc.

From the Cochrane library: Hygiene and emollient interventions for maintaining skin integrity in older people in hospital and residential care settings

To the Editor: Given the rapidly growing aging population utilizing hospital and residential care settings, which is expected to quadruple over the next 40 years,1 interventions for maintaining skin integrity among older people are of increasing importance. Loss of collagen and elastin throughout aging causes increased rates of xerosis, skin fissuring, and pruritus, which diminish the quality of life and morbidity2; therefore, maintaining skin integrity in older people is essential for ensuring health and well-being, while preventing conditions such as pressure ulcers and avoiding extended wound care.

Skin Anti-Aging Potential of Ipomoea pes-caprae Ethanolic Extracts on Promoting Cell Proliferation and Collagen Production in Human Fibroblasts (CCD-986sk Cells).

Collagen loss in the skin dermis is a major cause of age-related changes to the skin. Natural phytochemical substances are desirable for the prevention of skin aging and the formation of wrinkles. Ipomoea pes-caprae (IPC) has been utilized for nutritional and therapeutic purposes, and its extract contains collagenase inhibitory activity while causing no cytotoxicity. The purpose of this study was to examine the impact of IPC extracts on cell proliferation and collagen production in human fibroblasts (CCD-986sk cells). IPC leaves were macerated in 70% and 95% ethanol and the chemical composition of the resulting extracts (IPC70 and IPC95) were determined using high performance liquid chromatography (HPLC). The bioactivity of IPC extracts was examined in CCD-986sk cells, including antioxidant capacity, inhibition of collagenase, effects on cell proliferation and collagen production, as well as wound healing using an in vitro scratch test. Changes in expression of collagen type I (COL1A1), tumor growth factor beta 1 (TGFB1), and beta-fibroblast growth factor (FGF2) genes were also evaluated. The antioxidant and collagenase inhibitory properties of IPC extracts were associated with 3,5-di-caffeoylquinic acid, chlorogenic acid, and ferulic acid. IPC extracts at noncytotoxic concentrations significantly increased cell proliferation, collagen production, and wound healing. These effects appear linked to the upregulation of COL1A1, TGFB1, and FGF2 genes. The bioactivity of the IPC70 extract was greater than that for IPC95. This is useful in cosmeceutical applications for human skin aging. Our findings indicate that IPC extracts have the potential for use in skin anti-aging cosmeceutical preparations.

618 Macrophage depletion preserves dermal collagen in UVB exposed mice

We previously reported that anti-TNFα antibodies (etanercept) block UVB-induced recruitment of neutrophils and macrophages (MΦ) into the dermis in mice. Paradoxically, etanercept accelerates loss of dermal collagen. To examine the role of MΦ in dermal collagen alteration during UVB exposure, we depleted MΦ in mice. C57BL/6J mice were treated with (0.15 ml) of Clophosome-A-Clodronate Liposomes (CCL) i.p. twice, 5 and 3 days before UVB exposure. We had 4 groups- sham, sham+CCL, UVB- and UVB+CCL-treated mice.

A non-retinol retinoic acid receptor-γ (RAR-γ/NR1B3) selective agonist, tectorigenin, can effectively inhibit the ultraviolet A-induced skin damage.

Long-term ultraviolet (UV) exposure can cause inflammation, pigmentation and photoaging. All-trans retinoic acid (ATRA/tretinoin) is a commonly used retinoic acid receptor (RAR) agonist in the clinical treatment of UV-induced skin problems. However, the use of such drugs is often accompanied by systemic adverse reactions caused by nonspecific activation of RARs. Therefore, this study was designed to screen for a novel RAR-γ-selective agonist with high safety. Molecular docking, dynamic simulation and Biacore were used to screen and identify novel RAR-γ-selective agonists. RT-PCR, ELISA, western blotting, immunofluorescence staining, flow cytometry and proteomic analysis were used to detect the effects of these novel RAR-γ selective agonists on UVA-induced inflammation and photoaging cell models. UVA-induced mouse models were used to evaluate the effects of tectorigenin on skin repair, ageing and inflammation. Tectorigenin is a novel RAR-γ-selective agonist, which inhibits UV-induced oxidative damage, inflammatory factor release and matrix metalloproteinase (MMP) production. Tectorigenin can also reverse the UVA-induced loss of collagen. The results of the signalling pathway research showed that tectorigenin mainly affects the MAPK/JNK/AP-1 pathway. In animal experiments, tectorigenin showed better anti-inflammatory and anti-photoaging effects, and caused less skin irritation than ATRA. Nano-particle loaded tectorigenin significantly improved the utilization of tectorigenin. Tectorignen is a non-retinol RAR-γ-selective agonist that can inhibit UV-induced skin damage and could be developed as a safe pharmaceutical component for the prevention of photoaging and skin inflammation.

Loss of core-fucosylation of SPARC impairs collagen binding and contributes to COPD

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease with high morbidity and mortality worldwide. Although several mechanisms to account for deleterious immune effects were proposed, molecular description for the underlying alveolar structural alterations for COPD is lacking. Here, silencing of α1,6-fucosyltransferase (Fut8), the enzyme for core-fucosylation and highly expressed in lung stem cells, resulted in alveolar structural changes in lung organoids, recapitulating COPD. Site-specific mass spectrometry analysis demonstrated that the secreted protein acidic and rich in cysteine (SPARC), which binds collagen, contains a core-fucosylation site in its VCSNDNcfK glycopeptide. Biacore assay showed markedly reduced collagen binding of SPARC lacking core fucosylation. Molecular dynamics analysis revealed that core fucosylation of SPARC-induced dynamic conformational changes in its N-glycan, allowing terminal galactose and N-acetylglucosamine to interact with K150, P261 and H264 residues, thereby promoting collagen binding. Site-specific mutagenesis of these residues also resulted in low affinity for collagen binding. Moreover, loss of collagen and decline of core fucosylation were observed in COPD lung tissues. These findings provide a new mechanistic insight into the role of core fucosylation of SPARC in cell–matrix communication and contribution to the abnormal alveolar structures in COPD.

ARTERIAL STIFFNESS ASSESSMENT IN DIABETIC PATIENTS IN A CARDIOLOGY CLINIC

Objective: Arterial stiffness is a complex phenomenon characterized by decreased compliance of the great arteries. In diabetes, the arterial wall undergoes a series of biomechanical changes, which can result in arterial stiffness. The mechanisms of these structural and functional arterial alterations in diabetes include insulin resistance, collagen accumulation due to inadequate enzymatic glycation, endothelial and autonomic nervous system dysfunction. Increased arterial stiffness is a marker of cardiovascular risk in diabetic patients. We aimed to evaluate the arterial stiffness of diabetic pateients in a private cardiology clinic Design and method: We evaluated 46 patients in cardiology service, who underwent central pressure assessment with the Mobil O’Graph device. All additional information about the patients conditions were taken from their medical records. Results: A total of 46 patients underwent the examination, being 26 of them women (56%), with a mean age of 58.93 years (+-35). Of these patients, 22 (47.8%) were diabetic, reported by their medical records. The mean central systolic pressure of diabetic patients was 142.9mmHg (+-35.1) and the central diastolic pressure was 86.9mmHg (+-19.9). The mean pulse wave velocity was 9.68 (+-5.31), with 11 (50%) above the normal value, according to the Brazilian Guideline of Hypertension 2020. Conclusions: As seen in the analyzed patients, diabetic patients are at high risk for an increase in arterial stiffness. This is possibly because the mechanisms that cause changes in endothelial collagen loss, such as advanced glycation end products and the inhibitor of formation of these products, aminoguanidine, are exacerbated in diabetic patients. The importance of assessing arterial stiffness, through pulse wave velocity, in diabetic patients is evident.

Bio-orthogonal Click Chemistry Methods to Evaluate the Metabolism of Inflammatory Challenged Cartilage after Traumatic Overloading.

During traumatic joint injuries, impact overloading can cause mechanical damage to the cartilage. In the following inflammation phase, excessive inflammatory cytokines (e.g., interleukin-1β (IL-1β)) can act on chondrocytes, causing over-proliferation, apoptosis, and extracellular matrix (ECM) degradation that can lead to osteoarthritis. This study investigated the combined effects of traumatic overloading and IL-1β challenge on the metabolic activities of chondrocytes. Bovine cartilage explants underwent impact overloading followed by IL-1β exposure at a physiologically relevant dosage (1 ng/mL). New click chemistry-based methods were developed to visualize and quantify the proliferation of in situ chondrocytes in a nondestructive manner without the involvement of histological sectioning or antibodies. Click chemistry-based methods were also employed to measure the ECM synthesis and degradation in cartilage explants. As the click reactions are copper-free and bio-orthogonal, i.e., with negligible cellular toxicity, cartilage ECM was cultured and studied for 6 weeks. Traumatic overloading induced significant cell death, mainly in the superficial zone. The high number of dead cells reduced the overall proliferation of chondrocytes as well as the synthesis of glycosaminoglycan (GAG) and collagen contents, but overloading alone had no effects on ECM degradation. IL-1β challenge had little effect on cell viability, proliferation, or protein synthesis but induced over 40% GAG loss in 10 days and 61% collagen loss in 6 weeks. For the overloaded samples, IL-1β induced greater degrees of degradation, with 68% GAG loss in 10 days and 80% collagen loss in 6 weeks. The results imply a necessary immediate ease of inflammation after joint injuries when trauma damage on cartilage is present. The new click chemistry methods could benefit many cellular and tissue engineering studies, providing convenient and sensitive assays of metabolic activities of cells in native three-dimensional (3D) environments.

MO379: Collagen-Derived Peptides in CKD: A Link to Fibrosis

Abstract BACKGROUND AND AIMS Collagen is a major component of the extracellular matrix (ECM) and has an essential role in the onset and progression of fibrosis and chronic kidney disease (CKD). Collagen alpha-1(I) (col1a1) is the most abundant collagen type in humans and the involvement of col1a1in CKD onset and progression is well established. We aimed to assess in detail the association of urinary col1a1 fragments with the progression of CKD and ageing. METHOD About 5000 urinary peptidomic datasets from healthy participants and CKD patients were retrieved from the ‘Human Urinary Proteome Database’. Inclusion criteria were age &amp;gt;18 years and eGFR being available. Urinary col1a1 fragments were identified and their abundance and correlation with eGFR and age were investigated. RESULTS Of 707 specific col1a1 peptides, 63 were significantly and highly positively associated with eGFR, while only six peptides showed a significant and strong negative association. A similar tendency was observed for ageing, where the abundance of most of the 244 peptides significantly associated with age, decreased with increasing age. The ten most significantly correlated peptides associated with eGFR corrected for age or age in a cohort matched for eGFR are listed in the table. CONCLUSION The results show a strong association between the reduced abundance of urinary collagen peptides and loss of kidney function as well as ageing. The data suggest that the col1a1 peptides indicate reduced degradation of collagen in CKD and aging. The results further suggest that fibrosis, potentially also of other organs, may be the consequence of attenuation of collagen degradation, and not increased synthesis.

Antiaging Effects of a Poly Herbal Extract in Comparison with Vitamin E on Aging Induced Mice

Background: Herbal medicine has been used from antient times to defy aging as cleopatra used several herbs as a drink or topically and pomegranate was a main herb used in her system, it was named the fruit of immortality. Combining three herbs into one preparation is recommended to increase medicinal benefits while reducing toxicity and to obtain a synergistic effect. In this study we have found that a polyherbal (Apium graveolens, Carthamus tinctorius, Punica granatum) extract from Iraqi origin have gave a stronger effect than vitamin E. Aim: The aim of this study was to evaluate the effect of the poly herbal extract in vitro as an antiaging and antioxidant agent in comparison with vitamin E, which is considered as one of the most potent anti aging agents. Materials and methods: forty mice were orally treated and divided into 4 groups ( all were induced with D- Galactose for aging accept the positive control): the first group was positive control, the second was negative control while the third group was treated with vitamin E, and the last group with the polyherbal extract. Later a number of biochemical tests were conducted to evaluate its effectiveness including; test of catalase, GSH-PX, GHS and oxidative stress parameters Results: Our research showed that treated groups with the herbal extract showed great results compared the group treated with vitamin E. Lower levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) were shown to be associated with reduced levels of MMP-1 upregulation, collagen loss, and increased levels of Nrf2 nuclear accumulation. The polyherbal extract we found, upregulated Nrf2 and reduced ROS production and oxidative damage by D- Galactose. Conclusion: According to the results of our research, the polyherbal extract may be a promising candidate for the prevention of aging signs induced by the intake of D- Galactose. The antioxidant action of vitamin E (VE) makes it an essential nutrient and an important antioxidant to defy aging. Deficit (VED) of VE leads to central nervous system, reproductive and immunological disorders leading to aging. However, this study showed that the polyherbal extract we used gave much better results than vitamin E in preventing aging signs. Keywords: Biochemical analysis, Apium graveolens, Carthamus tinctorious, Punica granatum, Antiaging

Structural characterization and anti-photoaging activity of a polysaccharide from Sargassum fusiforme

In this study, a purified algal polysaccharide (P1) was isolated from Sargassum fusiforme and its structural characteristics and anti-photoaging activity were studied. Results showed that P1 had a molecular weight of 289 kDa and was mainly composed of mannuronic acid, guluronic acid and fucose with molar ratio of 7.67:2.35:1.00. The backbone of P1 was →4)-β-ManA-(1→4)-α-GulA-(1→4)-β-ManA-(1→4)-β-ManA-(1→4)-α-GulA-(1→4)-β-ManA-(1→3,4)-β-ManA-(1→ with a terminal group of α-Fucp-(1→ linked to O-3 position of →3,4)-β-ManA-(1→. In addition, P1 could inhibit the expressions of MMPs (MMP-1, MMP-3 and MMP-9) in the UVB-irradiated HaCaT cells, indicating that P1 could reduce collagen loss caused by UVB irradiation. It also reduced the contents of ROS and inflammatory factors (TNF-α, IL-6 and IL-1β), indicating that P1 could reduce the oxidative stress and inflammation response. Thus, Sargassum fusiforme polysaccharide P1 could be used as a potential functional food to relieve skin photoaging.

Protective Effect of Djulis (Chenopodium formosanum) Extract against UV- and AGEs-Induced Skin Aging via Alleviating Oxidative Stress and Collagen Degradation.

Skin aging is a complex process involving photoaging and glycation stress, which share some fundamental pathways and have common mediators. They can cause skin damage and collagen degradation by inducing oxidative stress and the accumulation of reactive oxygen species (ROS). Chenopodium formosanum (CF), also known as Djulis, is a traditional cereal in Taiwan. This study investigated the protection mechanisms of CF extract against ultraviolet (UV) radiation and advanced glycation end products (AGEs)-induced stress. The results indicated that CF extract had strong antioxidant and free radical scavenging effects. It could reduce UV-induced intracellular ROS generation and initiate the antioxidant defense system by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in human skin fibroblasts. CF extract modulated mitogen-activated protein kinase (MAPK) and transformed growth factor-beta (TGF-β) signaling pathways to alleviate oxidative stress-induced skin aging. Moreover, the results revealed that CF extract not only promoted collagen synthesis but also improved aging-induced collagen degradation. CF extract attenuated AGEs-induced ROS production and the upregulation of receptor for AGEs (RAGE). The overall results suggest that CF extract provides an effective anti-aging strategy by preventing skin damage from oxidative stress and collagen loss with potent antioxidant, anti-photoaging, and antiglycation activities.

TANTALUM OXIDE NANOPARTICLES FOR CONTRAST ENHANCED COMPUTED TOMOGRAPHY IMAGING OF CARTILAGE

Purpose: Contrast-enhanced computed tomography (CECT) allows detection of changes in cartilage structure and function via use of a contract agent, which diffuses into cartilage. The aim of this study is to investigate potential of a novel nanoparticle contrast agent for computed tomography (CT) diagnosis of osteoarthritis. An early indicator of cartilage degeneration is the loss of collagens and proteoglycans (PG) leading to enhanced tissue permeability and decreased tissue mechanical integrity.

Application of Nonsurgical Modalities in Improving Facial Aging.

Objective This review aims to summarize different kinds of applications of minimally invasive surgery in improving facial aging to provide a comprehensive and accurate introduction on the issue of esthetic treatment of facial skin. Overview. In the twentieth century, facial rejuvenation has become a new beauty trend. Facial cosmetology has entered a period of antiaging and rejuvenation therapies and microplastic surgery. The pursuit of beauty has promoted the development of minimally invasive plastic surgery. This review introduces the possible causes of facial aging and its related topics with a focus on facial injectable drugs, such as botulinum toxin, main filler materials (hyaluronic acid, calcium hydroxyapatite, poly L-lactic acid, collagen, autologous fat, and polymethyl methacrylate), and some current antiwrinkle technologies, such as thread lift and radiofrequency rhytidectomy. Conclusions Despite the difference in mechanisms of action, each technique can address facial aging involving the loss of collagen, displacement and enlargement of fat, and muscle relaxation. Combinations of these treatments can provide patients with reasonable, comprehensive, and personalized treatment plans.

Age-Related Downregulation of CCN2 Is Regulated by Cell Size in a YAP/TAZ-Dependent Manner in Human Dermal Fibroblasts: Impact on Dermal Aging

CCN2, a member of the CCN family of matricellular proteins, is a key mediator and biomarker of tissue fibrosis. We previously reported that CCN2 is significantly reduced in aged human dermis, which contributes to dermal aging through the downregulation of collagen production, the major structural protein in the skin. In this study, we investigated the underlying mechanisms of the age-related downregulation of CCN2 in human skin dermal fibroblasts. Dermal fibroblasts isolation and laser-capture microdissection‒coupled RT-PCR from human skin confirmed that age-related reduction of CCN2 expression is regulated by epigenetics. Mechanistic investigation revealed that age-related reduction of CCN2 is regulated by impaired dermal fibroblast spreading/cell size, which is a prominent feature of aged dermal fibroblasts in vivo. Gain-of-function and loss-of-function analysis confirmed that age-related downregulation of CCN2 is regulated by YAP/TAZ in response to reduced cell size. We further confirmed that restoration of dermal fibroblast size rapidly reversed the downregulation of CCN2 in a YAP/TAZ-dependent manner. Finally, we confirmed that reduced YAP/TAZ nuclear staining is accompanied by loss of CCN2 in aged human skin in vivo. Our data reveal a mechanism by which age-related reduction in fibroblast spreading/size drives YAP/TAZ-dependent downregulation of CCN2 expression, which in turn contributes to loss of collagen in aged human skin.