Geriatric Skin Research Articles

Evaluation of Clinical Knowledge Regarding Geriatric Skin Conditions among Thai Physicians

Objective: Assess the knowledge of common geriatric skin conditions in Thai physicians.Materials and Methods: This retrospective study was conducted among Thai physicians attending annual dermatology courses by the Dermatological Society of Thailand from 2016 to 2019. Data was assessed based on knowledge of diagnosis and management of common geriatric skin conditions.Results: A total of 197 participants, mainly general practitioners, were included. The highest percentage of correct diagnoses were benign erythematous, eczematous lesions (35.5%, senile purpura; 36.0%, xerotic eczema), and malignant diseases (35.5%, basal cell carcinoma; 27.4%, squamous cell carcinoma; 11.7%, subungual melanoma; 24.4%, acral lentiginous melanoma). In contrasts, the lowest percentage of correct diagnosis were premalignant diseases (0.5%, arsenical keratosis; 4.6%, actinic keratosis; 1.0% Bowen’s disease) and benign hypopigmented lesion (0.5%, stellate pseudoscar; 7.6%, idiopathic guttate hypomelanosis). Harmful treatment with systemic antifungal therapy was used in subungual melanoma (58.0%). Harmful management of senile comedone, subungual melanoma and acral lentiginous melanoma was significantly found in physicians given the incorrect diagnosis. (p = 0.027, p <0.001, p = 0.014, respectively).Conclusion: Most physicians recognized malignant lesions, benign erythematous or eczematous diseases in elderly skin. Surprisingly, almost all physicians couldn’t diagnose premalignant lesions and benign hypopigmented lesions.

Wounding Therapies for Prevention of Photocarcinogenesis.

The occurrence of non-melanoma skin cancer (NMSC) is closely linked with advanced age and ultraviolet-B (UVB) exposure. More specifically, the development of NMSC is linked to diminished insulin-like growth factor-1 (IGF-1) signaling from senescent dermal fibroblasts in geriatric skin. Consequently, keratinocyte IGF-1 receptor (IGF-1R) remains inactive, resulting in failure to induce appropriate protective responses including DNA repair and cell cycle checkpoint signaling. This allows UVB-induced DNA damage to proliferate unchecked, which increases the likelihood of malignant transformation. NMSC is estimated to occur in 3.3 million individuals annually. The rising incidence results in increased morbidity and significant healthcare costs, which necessitate identification of effective treatment modalities. In this review, we highlight the pathogenesis of NMSC and discuss the potential of novel preventative therapies. In particular, wounding therapies such as dermabrasion, microneedling, chemical peeling, and fractionated laser resurfacing have been shown to restore IGF-1/IGF-1R signaling in geriatric skin and suppress the propagation of UVB-damaged keratinocytes. This wounding response effectively rejuvenates geriatric skin and decreases the incidence of age-associated NMSC.

Histopathological spectrum of skin lesions in the elderly: Experience from a tertiary hospital in Southeast Nigeria

Background: There are only a few epidemiological studies published on skin disorders in the elderly within the Nigerian context and none from the Southeast Region of the country. In addition, none of these studies has considered the pattern and frequency of histopathologically diagnosed geriatric skin lesions. Hence, we attempted to determine the frequency as well as the age and gender distributions of histologically diagnosed dermatological diseases in geriatric population from skin biopsies submitted to the histopathology department of a tertiary care hospital in Southeast Nigeria. Materials and Methods: This is a cross-sectional retrospective hospital-based study involving all skin biopsies of patients 60 years and above, received at the Department of Histopathology, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria, from January 2004 to December 2019. Results: During the study period, 751 skin biopsies were received in the histopathology department. Of these, 142 were from patients who were older than 60 years. Thus, the overall share of geriatric patients was 18.9%. The mean age at presentation was 71.1 ± 8.6 years. The M: F was 1:1, and most of the patients belonged to the age group of 60–69 years (69 cases, 48.6%). The mean age of the male patients was 72.1 ± 9.5 years. In the female patients, it was 70.1 ± 7.5 years. The most common disease category was neoplasms (91, 64.1%). Most neoplasms were malignant. There were 67/142 (47.2%) malignant lesions. The most common was Squamous cell carcinoma (SCC) (30 cases) which is 21.1% of all geriatric skin biopsies and 44.8% of malignant skin biopsies. This is closely followed by melanoma (29 cases). Conclusion: Malignant neoplasms, benign neoplasms, and papulosquamous disorders are the three most common histologically diagnosed skin lesions in our geriatric population. The most common skin malignancies in this group of patients are SCC and malignant melanoma.

Geriatrics skin & homoeopathy

Skin is the largest gland of the body & it is the largest cover of the body. Here, the article deals with the skin of the geriatrics. The skin of the geriatrics is also a special area for Homoeopathy. Skin & Homoeopathy are intricately related as the fundamental cause of diseases as per Homoeopathy is the ‘Psoric miasm’ which manifest in the skin in the initial stages. Later, under favourable circumstances, it proceeds to affect the physical & mental aspects of the body through functional disturbances. Since the late 2019, the addition of COVID 19 to the plethora of geriatrics skin further emphasises the importance of the current article. The current article examines the contribution of Homoeopathy to deal with the clinical issues related to the geriatrics skin. The article traces the clinical aspects in its major forms & its implications on other aspects of the body. Thereafter, it deals with the subject of the changing face of the pattern of symptoms of geriatrics skin through the dimension of how, why, when, where and whom of these therapeutic patterns. Following that the burden of the geriatric care is explained through the social & economic impacts that it has exerted while perpetuating demographic issues. Taking cue from one of the elaborate & established books in the Homoeopathic world, it deals with what Homoeopathy had offered, is offering & the potential to offer in the future to deal with this important area of geriatric skin in normal times and as well as during the ongoing COVID pandemic.

Creatine and Nicotinamide Prevent Oxidant-Induced Senescence in Human Fibroblasts.

Dermal fibroblasts provide structural support by producing collagen and other structural/support proteins beneath the epidermis. Fibroblasts also produce insulin-like growth factor-1 (IGF-1), which binds to the IGF-1 receptors (IGF-1Rs) on keratinocytes to activate signaling pathways that regulate cell proliferation and cellular responses to genotoxic stressors like ultraviolet B radiation. Our group has determined that the lack of IGF-1 expression due to fibroblast senescence in the dermis of geriatric individuals is correlated with an increased incidence of skin cancer. The present studies tested the hypothesis that pro-energetics creatine monohydrate (Cr) and nicotinamide (NAM) can protect normal dermal human fibroblasts (DHF) against experimentally induced senescence. To that end, we used an experimental model of senescence in which primary DHF are treated with hydrogen peroxide (H2O2) in vitro, with senescence measured by staining for beta-galactosidase activity, p21 protein expression, and senescence associated secretory phenotype cytokine mRNA levels. We also determined the effect of H2O2 on IGF-1 mRNA and protein expression. Our studies indicate that pretreatment with Cr or NAM protects DHF from the H2O2-induced cell senescence. Treatment with pro-energetics post-H2O2 had no effect. Moreover, these agents also inhibited reactive oxygen species generation from H2O2 treatment. These studies suggest a potential strategy for protecting fibroblasts in geriatric skin from undergoing stress-induced senescence, which may maintain IGF-1 levels and therefore limit carcinogenesis in epidermal keratinocytes.

Randomized controlled trial of fractionated laser resurfacing on aged skin as prophylaxis against actinic neoplasia.

BACKGROUNDThe loss of insulin-like growth factor 1 (IGF-1) expression in senescent dermal fibroblasts during aging is associated with an increased risk of nonmelanoma skin cancer (NMSC). We tested how IGF-1 signaling can influence photocarcinogenesis during chronic UVB exposure to determine if fractionated laser resurfacing (FLR) of aged skin, which upregulates dermal IGF-1 levels, can prevent the occurrence of actinic keratosis (AK) and NMSC.METHODSA human skin/immunodeficient mouse xenografting model was used to test the effects of a small molecule inhibitor of the IGF-1 receptor on chronic UVB radiation. Subsequently, the durability of FLR treatment was tested on a cohort of human participants aged 65 years and older. Finally, 48 individuals aged 60 years and older with considerable actinic damage were enrolled in a prospective randomized clinical trial in which they underwent a single unilateral FLR treatment of one lower arm. Numbers of AKs/NMSCs were recorded on both extremities for up to 36 months in blinded fashion.RESULTSXenografting studies revealed that chronic UVB treatment with a topical IGF-1R inhibitor resulted in a procarcinogenic response. A single FLR treatment was durable in restoring appropriate UVB response in geriatric skin for at least 2 years. FLR resulted in sustained reduction in numbers of AKs and decreased numbers of NMSCs in the treated arm (2 NMSCs) versus the untreated arm (24 NMSCs).CONCLUSIONThe elimination of senescent fibroblasts via FLR reduced the procarcinogenic UVB response of aged skin. Thus, wounding therapies are a potentially effective prophylaxis for managing high-risk populations.TRIAL REGISTRATIONClinicalTrials.gov (NCT03906253).FUNDINGNational Institutes of Health, Veterans Administration.

Dermatoses among patients aged 60 years and above attending a tertiary referral center: A cross-sectional study from North Kerala

Objectives: With the rise in life expectancy at birth, geriatric population contributes to a significant proportion of those seeking medical aid. Skin problems in the elderly are very common and vary according to region and ethnicity. It is essential for dermatologists to have a better understanding of the pathophysiology of geriatric skin disorders to formulate quality management guidelines. This study was undertaken to document the frequency and the clinical pattern of various physiological and pathological changes in the elderly skin. Materials and Methods: A cross-sectional study was carried out in 200 consecutive patients aged 60 years and above and who attended the Dermatology outpatient clinic of a tertiary referral center in North Kerala. A pre-set pro forma was used to document the patient characteristics, the comorbidities, the medications used, and the clinical findings. Results: All the study participants (100%) had one or more dermatoses. The age of the study population ranged from 60 to 89 years (mean 67.7 ± 6.2 years). This was a female preponderant study with a female to male ratio of 1.4:1. Hypertension (36%), hyperlipidemia (27%) and diabetes mellitus (26%) were the common comorbidities observed. Graying of hair was the most common physiological change, followed by wrinkling. Pruritus was the most common presenting complaint (136, 68%). Statistically significant association was noted between xerosis and generalized pruritus. Fungal infections (30.5%) outnumbered other infections and infestations. Changes of severe photoaging were less frequent. One patient had skin malignancy (basal cell carcinoma). Significant association was noted between photoaging and male sex, smoking, and sun exposure. Limitations: Study conducted in a tertiary referral center not reflecting the status in the community was the major limitation. Conclusion: Photoaging and skin cancers are less frequent in darker skin type. Healthy lifestyle, nutritious diet, frequent application of emollient, better skin care, and judicious use of sunscreen can delay the process of cutaneous aging. More prospective studies in different population groups may go a long way in improving the current knowledge about the less known aspects of geriatric dermatoses.

Age and insulin-like growth factor-1 impact PCNA monoubiquitination in UVB-irradiated human skin

Nonmelanoma skin cancers occur primarily in individuals over the age of 60 and are characterized by an abundance of ultraviolet (UV) signature mutations in keratinocyte DNA. Though geriatric skin removes UV photoproducts from DNA less efficiently than young adult skin, it is not known whether the utilization of other prosurvival but potentially mutagenic DNA damage tolerance systems such as translesion synthesis (TLS) is altered in older individuals. Using monoubiquitination of the replicative DNA polymerase clamp protein PCNA (proliferating cell nuclear antigen) as a biochemical marker of TLS pathway activation, we find that UVB exposure of the skin of individuals over the age of 65 results in a higher level of PCNA monoubiquitination than in the skin of young adults. Furthermore, based on previous reports showing a role for deficient insulin-like growth factor-1 (IGF-1) signaling in altered UVB DNA damage responses in geriatric human skin, we find that both pharmacological inhibition of the IGF-1 receptor (IGF-1R) and deprivation of IGF-1 potentiate UVB-induced PCNA monoubiquitination in both human skin ex vivo and keratinocytes in vitro. Interestingly, though the TLS DNA polymerase Pol eta can accurately replicate the major photoproducts induced in DNA by UV radiation, we find that it fails to accumulate on chromatin in the absence of IGF-1R signaling and that this phenotype is correlated with increased mutagenesis in keratinocytes in vitro. Thus, altered IGF-1/IGF-1R signaling in geriatric skin may predispose epidermal keratinocytes to carry out a more mutagenic form of DNA synthesis following UVB exposure.

Pattern of Skin Diseases in Geriatric Population: Our Year-Long Experience from Nepal.

Introduction:The average life span has increased by about two decades in Nepal in last 30 years. With increasing longevity, geriatric health care is gaining much more importance. The statistical data regarding the geriatric skin disorders in Nepalese population is limited. The aim of this study to look for the patterns of skin diseases in the geriatric population of Nepal.Methodology:This is a retrospective, descriptive study where we reviewed the database of patients visiting the dermatology outpatient department of multispeciality teaching hospital in Nepal from August 2016 to July 2017. All patients from the age of 60 and above were included in the study. Data was analyzed using SPSS version 20. Chi square test was done where relevant.Result:Total of 918 patients were included in the study with mean age of 69 years. Most common presentation was that of dermatitis (32.2%) which was followed by infectious condition (29.4%), pruritus (7.4%), psoriasis (4.6%), urticaria (3.9%), miliaria (3.9%) and others. Among the dermatitis, 23% of the patients had hand or feet eczema and 23% had sebohrreic dermatitis. Variability according to weather was noticed with in presentation of sebohrreic dermatitis, dermatophytic infections, miliaria and herpes zoster.Conclusion:This study concludes that dermatitis, infections and pruritus are the most significant dermatological morbidities in our population. It highlights the need of zoster vaccine for our elderly population as it is not a part of the routine vaccination scheme in Nepal.

Dermatologic Lesions in Geriatric Patient with Diabetes Mellitus

Introduction: In geriatrics, there are changes in structure and function results in histopathological, physiological and clinical skin changes. The conditions can cause morbidity and decreases the quality of life of patients. This study was the first study that provide the characteristics of geriatric skin disorders in Dr. Mohammad Hoesin Hospital Palembang.
 Methods: This study was descriptive observational with cross-sectional design using total sampling method performed among patients in Geriatric Outpatient Clinic, Dermatology and Venereology Outpatient Clinic and geriatric inpatient room in Dr. Mohammad Hoesin Hospital on July-September 2019.
 Results: Physiological skin changes in geriatrics include xerosis cutis (13,95%), seborrheic keratosis (13,17%), guttate hypomelanosis (8,5%), senile lentigen (6,97%), freckle (2,32%), periorbital hyperpigmentation (1,55%), senile purpura (0,77%) and poikiloderma civatte (0,77%). The most skin disorder found were lichen simplex chronicus (11,1%), pressure ulcers (9,25%), senile pruritus (8,32%), asteatotic dermatitis (6.47%) and candidiasis (3,7%). The most common comorbid condition were diabetes mellitus in 16 patients (22,5%), CVD in 7 patients (9,9%), hypertension in 6 patients (8,5%), AKI in 6 patients (8,5 %), and HHD in 4 patients (5,6%). Diabetes mellitus was significantly associated with xerosis cutis (p = 0,0007), senile pruritus (p = 0,015), and guttate hypomelanosis (p = 0,016).
 Conclusion: The most physiological skin changes found in geriatric patients in Dr. Mohammad Hoesin Hospital were xerosis cutis, seborrheic keratosis, and guttate hypomelanosis, while skin disorder were lichen simplex chronicus, pressure ulcer, and senile pruritus. Diabetes mellitus was significantly associated with skin disorders.

637 Age and insulin-like growth factor-1 (IGF-1) status impact translesion synthesis (TLS) pathway activation in human keratinocytes and skin epidermis

Several studies have indicated that UV-induced DNA photoproducts are removed from epidermal genomic DNA at a slower rate in geriatric skin than in young adult skin. Such a situation may result in a greater need for the translesion synthesis (TLS) pathway of DNA replication, in which specialized DNA polymerases are recruited to sites of DNA damage to replicate across DNA adducts in either an error-free or error-prone manner. Here we show that skin epidermis from geriatric individuals (>65 years of age) exhibits higher levels of mono-ubiquitinated PCNA, a biochemical marker of TLS pathway activation, than the skin of young adults (aged 21-29) following exposure to 700 J/m2 of UVB light.

628 Evidence that wounding of geriatric skin which upregulates IGF-1 levels protects against both abnormal carcinogenic UVB responses as well as from the development of non-melanoma skin cancer

628 Evidence that wounding of geriatric skin which upregulates IGF-1 levels protects against both abnormal carcinogenic UVB responses as well as from the development of non-melanoma skin cancer

Insulin-like Growth Factor-1 Impacts p53 Target Gene Induction in UVB-irradiated Keratinocytes and Human Skin.

The tumor suppressor protein p53 limits mutagenesis in response to ultraviolet-B (UVB) light exposure by activating the transcription of genes that mitigate the damaging effects of UVB radiation on DNA. Because most nonmelanoma skin cancers (NMSCs) occur in older individuals, it is important to understand the process of mutagenesis in the geriatric skin microenvironment. Based on previous studies demonstrating that geriatric skin expresses lower levels of the growth factor insulin-like growth factor-1 (IGF-1) than young adult skin, a role for IGF-1 in the regulation of p53 target genes was investigated in both human keratinocytes in vitro and human skin explants ex vivo. The products of the p53 target genes p21 and DNA polymerase eta (pol η) were found to be increased by UVB exposure in both experimental systems, and this induction was observed to be partially abrogated by depriving keratinocytes of IGF-1 in vitro or by the treatment of keratinocytes in vitro and human skin explants with an IGF-1 receptor antagonist. Because p21 and pol η function to limit mutagenic DNA replication following UVB exposure, these results suggest that NMSC risk in geriatric populations may be due to age-dependent decreases in IGF-1 signaling that disrupt p53 function in the skin.

Wounding with a microneedling device corrects the inappropriate ultraviolet B radiation response in geriatric skin.

Non-melanoma skin cancer primarily affects geriatric patients as evidenced by the fact that only 20% of these cancers are diagnosed in patients under the age of 60years. Of importance, geriatric skin responds to procarcinogenic ultraviolet B radiation (UVB) in a manner that permits the establishment of tumor cells. Recent studies have indicated that wounding of geriatric skin with fractionated resurfacing lasers and dermabrasion upregulates fibroblast production of insulin-like growth factor-1 (IGF-1) and normalizes the procarcinogenic acute UVB response consisting of basal keratinocytes proliferating while still harboring unrepaired DNA damage. The present studies tested the ability of wounding with a commercially available microneedling device to upregulate IGF-1 levels and normalize the geriatric UVB response. Geriatric volunteers were treated with a microneedling device on buttock skin and 3months later the IGF-1 levels and UVB responses tested in wounded vs control skin. Wounding via microneedling upregulated IGF-1 and resulted in lower levels of basal keratinocytes proliferating with unrepaired DNA damage. The ability of microneedling to protect against the formation of UVB-damaged proliferating keratinocytes indicates the potential of this wounding modality to reduce aging-associated non-melanoma skin cancer.

Gene Expression Changes In Young and Geriatric Skin

Gene Expression Changes In Young and Geriatric Skin

759 Protection of geriatric skin from abnormal procarcinogenic UVB responses by dermal wounding strategies which upregulate IGF-1 levels

UVB irradiation causes specific DNA-damage to keratinocytes that can lead to cancer-causing mutations if they are allowed to persist in proliferating cells. Previously, we demonstrated that the activation status of the insulin-like growth factor-1 receptor (IGF-1R) regulates the cellular response of keratinocytes to UVB exposure, both in vitro and in vivo. Briefly, geriatric skin is deficient in IGF-1 expression resulting in an aberrant IGF-1R-dependent UVB response consisting of basal keratinocytes proliferating while still harboring unrepaired DNA damage (Ki-67- and thymine dimer-co-expressing cells). This abnormal UVB response contributes to the development of aging-associated squamous cell carcinoma. As the dermal fibroblast is the source of IGF-1 in skin, and aging results in senescent fibroblasts which produce less IGF-1, we have used wounding strategies which enhance IGF-1 expression in an attempt to normalize the abnormal, pro-carcinogenic geriatric UVB response. Here we demonstrate that localized wounding of geriatric skin with fractionated laser resurfacing (FLR) or topical use of a dermaroller device results in decreased numbers of senescent fibroblasts and increased levels of IGF-1. Moreover, acute UVB treatment of previously wounded skin results in decreased numbers of basal keratinocytes co-expressing thymine dimers and the proliferative antigen Ki-67, in comparison to UVB-treated control (not wounded) skin. Long-term studies reveal that the wounding effect induced by FLR appears to be durable, in that we note statistically increased levels of IGF-1 mRNA and decreased numbers of basal keratinocytes expressing both thymine dimers and Ki-67 in geriatric subjects at one and two years post-treatment. These studies suggest that wounding procedures could protect geriatric skin from the abnormal pro-carcinogenic UVB response associated with aging.

Effectiveness of Fractionated Laser Resurfacing to Protect Geriatric Skin From Actinic Neoplasia

Effectiveness of Fractionated Laser Resurfacing to Protect Geriatric Skin From Actinic Neoplasia

Impact of Age and Insulin-Like Growth Factor-1 on DNA Damage Responses in UV-Irradiated Human Skin.

The growing incidence of non-melanoma skin cancer (NMSC) necessitates a thorough understanding of its primary risk factors, which include exposure to ultraviolet (UV) wavelengths of sunlight and age. Whereas UV radiation (UVR) has long been known to generate photoproducts in genomic DNA that promote genetic mutations that drive skin carcinogenesis, the mechanism by which age contributes to disease pathogenesis is less understood and has not been sufficiently studied. In this review, we highlight studies that have considered age as a variable in examining DNA damage responses in UV-irradiated skin and then discuss emerging evidence that the reduced production of insulin-like growth factor-1 (IGF-1) by senescent fibroblasts in the dermis of geriatric skin creates an environment that negatively impacts how epidermal keratinocytes respond to UVR-induced DNA damage. In particular, recent data suggest that two principle components of the cellular response to DNA damage, including nucleotide excision repair and DNA damage checkpoint signaling, are both partially defective in keratinocytes with inactive IGF-1 receptors. Overcoming these tumor-promoting conditions in aged skin may therefore provide a way to lower aging-associated skin cancer risk, and thus we will consider how dermal wounding and related clinical interventions may work to rejuvenate the skin, re-activate IGF-1 signaling, and prevent the initiation of NMSC.

Insulin-like Growth Factor 1 Receptor Signaling Is Required for Optimal ATR-CHK1 Kinase Signaling in Ultraviolet B (UVB)-irradiated Human Keratinocytes

UVB wavelengths of light induce the formation of photoproducts in DNA that are potentially mutagenic if not properly removed by the nucleotide excision repair machinery. As an additional mechanism to minimize the risk of mutagenesis, UVB-irradiated cells also activate a checkpoint signaling cascade mediated by the ATM and Rad3-related (ATR) and checkpoint kinase 1 (CHK1) kinases to transiently suppress DNA synthesis and cell cycle progression. Given that keratinocytes in geriatric skin display reduced activation of the insulin-like growth factor 1 receptor (IGF-1R) and alterations in DNA repair rate, apoptosis, and senescence following UVB exposure, here we used cultured human keratinocytes in vitro and skin explants ex vivo to examine how IGF-1R activation status affects ATR-CHK1 kinase signaling and the inhibition of DNA replication following UVB irradiation. We find that disruption of IGF-1R signaling with small-molecule inhibitors or IGF-1 withdrawal partially abrogates both the phosphorylation and activation of CHK1 by ATR and the accompanying inhibition of chromosomal DNA synthesis in UVB-irradiated keratinocytes. A critical protein factor that mediates both ATR-CHK1 signaling and nucleotide excision repair is replication protein A, and we find that its accumulation on UVB-damaged chromatin is partially attenuated in cells with an inactive IGF-1R. These results indicate that mutagenesis and skin carcinogenesis in IGF-1-deficient geriatric skin may be caused by defects in multiple cellular responses to UVB-induced DNA damage, including through a failure to properly suppress DNA synthesis on UVB-damaged DNA templates.

Insulin-like growth factor-1 receptor regulates repair of ultraviolet B-induced DNA damage in human keratinocytes in vivo

The activation status of the insulin-like growth factor-1 receptor (IGF-1R) regulates the cellular response of keratinocytes to ultraviolet B (UVB) exposure, both in vitro and in vivo. Geriatric skin is deficient in IGF-1 expression resulting in an aberrant IGF-1R-dependent UVB response which contributes to the development of aging-associated squamous cell carcinoma. Furthermore, our lab and others have reported that geriatric keratinocytes repair UVB-induced DNA damage less efficiently than young adult keratinocytes. Here, we show that IGF-1R activation influences DNA damage repair in UVB-irradiated keratinocytes. Specifically, in the absence of IGF-1R activation, the rate of DNA damage repair following UVB-irradiation was significantly slowed (using immortalized human keratinocytes) or inhibited (using primary human keratinocytes). Furthermore, inhibition of IGF-1R activity in human skin, using either ex vivo explant cultures or in vivo xenograft models, suppressed DNA damage repair. Primary keratinocytes with an inactivated IGF-1R also exhibited lower steady-state levels of nucleotide excision repair mRNAs. These results suggest that deficient UVB-induced DNA repair in geriatric keratinocytes is due in part to silenced IGF-1R activation in geriatric skin and provide a mechanism for how the IGF-1 pathway plays a role in the initiation of squamous cell carcinoma in geriatric patients.