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Racial similarities and differences in gene expression related to aging – the Multidecade and Ethnicity Study
3778
3445
New biological insights into skin aging around the eye Michael Flagler, PhD, Procter & Gamble, Mason, OH, United States; Karen Osorio, PhD, Procter & Gamble, Mason, OH, United States; Joe Kaczvinsky, PhD, Procter & Gamble, Cincinnati, OH, United States; Anna Dowdy, MS, Procter & Gamble, Cincinnati, OH, United States; Rosemarie Osborne, PhD, Procter & Gamble, Cincinnati, OH, United States; Heather Rocchetta, PhD, Procter & Gamble, Mason, OH, United States; Bradley Jarrold, MS, Procter & Gamble, Mason, OH, United States; Makio Tamura, Procter & Gamble, Mason, OH, United States; Raghu Kainkaryam, Procter & Gamble, Mason, OH, United States; Steven Zhao, Procter & Gamble, Mason, OH, United States
Racial similarities and differences in gene expression related to aging e the Multidecade and Ethnicity Study Rosemarie Osborne, PhD, The Procter & Gamble Company, Mason, OH, United States; Makio Tamura, PhD, The Procter & Gamble Company, Mason, OH, United States; Bradley Jarrold, MS, The Procter & Gamble Company, Mason, OH, United States; Emily Conley, PhD, 23andMe, Mountain View, CA, United States; Joyce Tung, PhD, 23andMe, Mountain View, CA, United States; Charles Bascom, PhD, The Procter & Gamble Company, Mason, OH, United States; Robert Isfort, PhD, The Procter & Gamble Company, Mason, OH, United States; Heather Rocchetta, PhD, The Procter & Gamble Company, Mason, OH, United States; Maria AloraPalli, MD, Harvard Medical School & Massachusetts General Hospital, Boston, MA, United States; Alexa Kimball, MD, Harvard Medical School & Massachusetts General Hospital, Boston, MA, United States We have reported previously the progressive, age-related changes in gene expression that occur in the skin of white women (Fitzpatrick I-III with majority Northern European ancestry confirmed by genotyping) from 20 to 70 years old in the Multi-decade & Ethnicity (MDE) Study. In order to understand similarities and differences associated with skin aging across different ethnicities, we evaluated also African American women in the age groups of 20-24, 40-44, and 60-64 years old (Fitzpatrick grades of V and VI, majority West African ancestry), with approximately 25 volunteers in each age decile. Skin samples were obtained from both photoexposed (face, outer forearm) and photoprotected (buttocks) body sites. The degree of photoaging was confirmed by histological assessment of elastosis, which was marked in photoexposed skin of 40+ year old white women, but relatively absent in African American skin. RNA was extracted from either full thickness or laser capture microdissected skin samples, and transcriptomics profiling was conducted using Affymetrix HG-U219 gene arrays with bioinformatics focused on gene set enrichment analysis of skin-related biological processes. Facial epidermis significantly decreased in thickness with age in white women, along with decreased expression of genes related to barrier formation. In African American women, epidermal thickness was constant with age with little effect on gene expression related to barrier formation. Proteasome and protein degradation activity increased with age in facial epidermis of white but not African American women; this may reflect increased degradation of damaged cellular components with aging in the white skin. Cellular senescence increased markedly with age in white women in both epidermis and dermis, especially in photoexposed body sites, and also increased in African American women but to a lesser extent. These results suggest that certain aging processes, such as cellular senescence may be common across races, and processes related to barrier formation and proteasome activity may change with age in ethnicspecific patterns; this is being evaluated further in the skin of Chinese and Hispanic women.
Skin aging in the area around the eye is highly associated with the overall perception of facial aging. Some of the aging phenotypes of skin around the eye are unique from other sites on the face, and include such diverse manifestations as fine lines, deep wrinkles, puffiness, dark circles, and sagging. We hypothesize that the biological processes underlying the signs of aging around the eye are different than those that occur at other facial sites. The objective of this work was to gain insights into the sources and etiologies of the visual differences observed with skin aging around the eye compared to other facial sites. To accomplish this, we performed two large human clinical studies in which subjects were recruited for specific eye area phenotypes. Tissue samples were collected from multiple periorbital locations (upper and lower eye lids, Crow’s feet and under eye), as well as other facial sites for comparison. Biological sampling was coupled with measures of skin appearance and with measures of skin functional properties, enabling correlation of molecular changes to visual and physical properties of the skin. Gene chip analysis (AffyMetrix HG-U219 gene arrays) of isolated dermis from multiple facial biopsy sites were analyzed using a signature of 400 consensus genes, the expression levels of which have been demonstrated to be universal indicators of dermal aging independent of epithelial tissue source or body site (GenEx Age model). The results indicated that the skin around the eye ages earlier than other sites on the face by this measure. In support of this finding, the skin around the eye exhibited lower elasticity than other facial sites, as determined by cutometry. Understanding the biological pathways specific to aging of features around the eye will enable development of specific solutions to proactively address these features. Supported 100% by Procter & Gamble.
Supported 100% by The Procter & Gamble Company.
3717 Pattern of nonsteroidal antiinflammatory drugeinduced cutaneous adverse drug eruption in the elderly Papapit Tuchinda, MD, Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Leena Chularojanamontri, MD, Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Pattriya Chanyachailert, MD, Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Kowit Jongjarearnprasert, MS, Department of Pharmacy, Siriraj Hospital, Mahidol University, Bangkok, Thailand; Panadda Uthaitas, MS, Department of Pharmacy, Siriraj Hospital, Mahidol University, Bangkok, Thailand; Kanokvalai Kulthanan, MD, Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
ARTS, HISTORY, & HUMANITIES OF DERMATOLOGY 3398 Dermatologic ailments in the white House Stephanie Mlacker, University of Miami, Miami, FL, United States; Adam Aldahan, University of Miami, Miami, FL, United States; Vidhi Shah, University of Miami, Miami, FL, United States; Keyvan Nouri, MD, University of Miami, Miami, FL, United States
Methods: A retrospective analysis was conducted involving elderly patients age 60 years and older with cutaneous ADRs suspected from NSAIDs from 2004 to 2014. Demographic data, concurrent medications, clinical course of cutaneous ADRs and possible causative drug were analyzed. Results: One hundred and one patients were included in the study. The mean age was 67.5 years and the cutaneous ADRs occurred in more women (65%) than men (35%). Etoricoxib was the most common suspected drug. Single and multiple NSAIDs reactors were identified in 91.1% and 8.9%, respectively. Angioedema with and without urticaria was the most common cutaneous ADRs in the elderly (39.6%) followed by maculopapular rash (18.8%). Forty one patients (40.6%) were categorized as serious ADRs. Almost all of the patients who developed serious reactions (97.5%) were diagnosed as angioedema with or without urticaria including anaphylaxis. Conclusion: Age-related pharmacokinetics alteration may predispose to severe ADRs from NSAIDs. This study could promote rational drug used and awareness of NSAIDs-induced ADRs in elderly patients.
American history encompasses a wide spectrum of dermatologic pathology that has affected past Presidents of the United States and their families. America’s founding father, George Washington, developed a ‘‘malignant carbuncle’’ on his left hip during his first year as president, requiring incision and drainage. James Madison developed frostbite on his nose after campaigning outside for the First Congress in 1788. A few days after delivering the Gettysburg Address, Abraham Lincoln developed ‘‘dusky red spots about the forehead,’’ which after spreading to his face and extremities, evolved into an acneiform appearance, coinciding with a smallpox epidemic. One of America’s Civil War heroes, Ulysses Grant, developed a cancerous growth at the base of his tongue in 1884; this occurred after many years of heavy drinking and smoking, inevitably leading to his unfavorable demise. Similarly, Grover Cleveland developed a malignancy on the left side of his jaw, involving the soft palate, and underwent a secret operation for its removal in 1893. In 1892, Rutherford B. Hayes developed dermatitis, involving his hands and face secondary to his exposure to poison ivy while pruning trees. Franklin D. Roosevelt’s pigmented nevus, located above his left eyebrow, no longer appeared in photographs after 1943, leading people to believe that it had been removed. The importance of this subtlety was noted after the president’s fatal seizure in 1945, raising questions regarding melanoma as the possible culprit. John F. Kennedy was diagnosed with Addison’s disease in 1947, years before serving as president. Although Kennedy exuded vitality with his youthful, tanned-like appearance, the hyperpigmentation of his face was actually a manifestation of his autoimmune condition. Lyndon Johnson underwent a clandestine procedure in 1967 in order to remove a basal cell carcinoma from his left ankle. Similarly, Ronald Reagan had basal cell carcinomas removed both during, and in the years following his presidency; moreover, his daughter, Maureen Reagan, subsequently passed away due to systemic melanoma metastases. Finally, it is well known that Bill Clinton has long suffered from rosacea and additionally received treatment for actinic keratosis and basal cell carcinoma. As revealed throughout American history, dermatology can indeed have an impact on anyone’s life, including the lives of prominent political leaders.
Commercial support: None identified.
Commercial support: None identified.
Background: Elderly people are commonly prescribed with polypharmacy due to multiple medical conditions which are associated with the risks for drug hypersensitivity. In addition, pharmacodynamics and pharmacokinetics alterations, including decreasing hepatic drug clearance and the decline of renal function, are also capable of contributing to the particularly risk for adverse drug reactions (ADRs) in elderly. Nonsteroidal antiinflammatory drugs (NSAIDs) are one of the most commonly prescribed medications, and about half of NSAID prescriptions are for elderly patients. However, the clinical knowledge of NSAID-induced cutaneous ADRs in elderly is limited. Objective: The aim of this study was to determine the association between the patient histories, clinical course, and causative NSAIDs drugs which contributed to cutaneous ADRs in the elderly.
AB28
J AM ACAD DERMATOL
MAY 2016
3445
New biological insights into skin aging around the eye Michael Flagler, PhD, Procter & Gamble, Mason, OH, United States; Karen Osorio, PhD, Procter & Gamble, Mason, OH, United States; Joe Kaczvinsky, PhD, Procter & Gamble, Cincinnati, OH, United States; Anna Dowdy, MS, Procter & Gamble, Cincinnati, OH, United States; Rosemarie Osborne, PhD, Procter & Gamble, Cincinnati, OH, United States; Heather Rocchetta, PhD, Procter & Gamble, Mason, OH, United States; Bradley Jarrold, MS, Procter & Gamble, Mason, OH, United States; Makio Tamura, Procter & Gamble, Mason, OH, United States; Raghu Kainkaryam, Procter & Gamble, Mason, OH, United States; Steven Zhao, Procter & Gamble, Mason, OH, United States
Racial similarities and differences in gene expression related to aging e the Multidecade and Ethnicity Study Rosemarie Osborne, PhD, The Procter & Gamble Company, Mason, OH, United States; Makio Tamura, PhD, The Procter & Gamble Company, Mason, OH, United States; Bradley Jarrold, MS, The Procter & Gamble Company, Mason, OH, United States; Emily Conley, PhD, 23andMe, Mountain View, CA, United States; Joyce Tung, PhD, 23andMe, Mountain View, CA, United States; Charles Bascom, PhD, The Procter & Gamble Company, Mason, OH, United States; Robert Isfort, PhD, The Procter & Gamble Company, Mason, OH, United States; Heather Rocchetta, PhD, The Procter & Gamble Company, Mason, OH, United States; Maria AloraPalli, MD, Harvard Medical School & Massachusetts General Hospital, Boston, MA, United States; Alexa Kimball, MD, Harvard Medical School & Massachusetts General Hospital, Boston, MA, United States We have reported previously the progressive, age-related changes in gene expression that occur in the skin of white women (Fitzpatrick I-III with majority Northern European ancestry confirmed by genotyping) from 20 to 70 years old in the Multi-decade & Ethnicity (MDE) Study. In order to understand similarities and differences associated with skin aging across different ethnicities, we evaluated also African American women in the age groups of 20-24, 40-44, and 60-64 years old (Fitzpatrick grades of V and VI, majority West African ancestry), with approximately 25 volunteers in each age decile. Skin samples were obtained from both photoexposed (face, outer forearm) and photoprotected (buttocks) body sites. The degree of photoaging was confirmed by histological assessment of elastosis, which was marked in photoexposed skin of 40+ year old white women, but relatively absent in African American skin. RNA was extracted from either full thickness or laser capture microdissected skin samples, and transcriptomics profiling was conducted using Affymetrix HG-U219 gene arrays with bioinformatics focused on gene set enrichment analysis of skin-related biological processes. Facial epidermis significantly decreased in thickness with age in white women, along with decreased expression of genes related to barrier formation. In African American women, epidermal thickness was constant with age with little effect on gene expression related to barrier formation. Proteasome and protein degradation activity increased with age in facial epidermis of white but not African American women; this may reflect increased degradation of damaged cellular components with aging in the white skin. Cellular senescence increased markedly with age in white women in both epidermis and dermis, especially in photoexposed body sites, and also increased in African American women but to a lesser extent. These results suggest that certain aging processes, such as cellular senescence may be common across races, and processes related to barrier formation and proteasome activity may change with age in ethnicspecific patterns; this is being evaluated further in the skin of Chinese and Hispanic women.
Skin aging in the area around the eye is highly associated with the overall perception of facial aging. Some of the aging phenotypes of skin around the eye are unique from other sites on the face, and include such diverse manifestations as fine lines, deep wrinkles, puffiness, dark circles, and sagging. We hypothesize that the biological processes underlying the signs of aging around the eye are different than those that occur at other facial sites. The objective of this work was to gain insights into the sources and etiologies of the visual differences observed with skin aging around the eye compared to other facial sites. To accomplish this, we performed two large human clinical studies in which subjects were recruited for specific eye area phenotypes. Tissue samples were collected from multiple periorbital locations (upper and lower eye lids, Crow’s feet and under eye), as well as other facial sites for comparison. Biological sampling was coupled with measures of skin appearance and with measures of skin functional properties, enabling correlation of molecular changes to visual and physical properties of the skin. Gene chip analysis (AffyMetrix HG-U219 gene arrays) of isolated dermis from multiple facial biopsy sites were analyzed using a signature of 400 consensus genes, the expression levels of which have been demonstrated to be universal indicators of dermal aging independent of epithelial tissue source or body site (GenEx Age model). The results indicated that the skin around the eye ages earlier than other sites on the face by this measure. In support of this finding, the skin around the eye exhibited lower elasticity than other facial sites, as determined by cutometry. Understanding the biological pathways specific to aging of features around the eye will enable development of specific solutions to proactively address these features. Supported 100% by Procter & Gamble.
Supported 100% by The Procter & Gamble Company.
3717 Pattern of nonsteroidal antiinflammatory drugeinduced cutaneous adverse drug eruption in the elderly Papapit Tuchinda, MD, Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Leena Chularojanamontri, MD, Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Pattriya Chanyachailert, MD, Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Kowit Jongjarearnprasert, MS, Department of Pharmacy, Siriraj Hospital, Mahidol University, Bangkok, Thailand; Panadda Uthaitas, MS, Department of Pharmacy, Siriraj Hospital, Mahidol University, Bangkok, Thailand; Kanokvalai Kulthanan, MD, Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
ARTS, HISTORY, & HUMANITIES OF DERMATOLOGY 3398 Dermatologic ailments in the white House Stephanie Mlacker, University of Miami, Miami, FL, United States; Adam Aldahan, University of Miami, Miami, FL, United States; Vidhi Shah, University of Miami, Miami, FL, United States; Keyvan Nouri, MD, University of Miami, Miami, FL, United States
Methods: A retrospective analysis was conducted involving elderly patients age 60 years and older with cutaneous ADRs suspected from NSAIDs from 2004 to 2014. Demographic data, concurrent medications, clinical course of cutaneous ADRs and possible causative drug were analyzed. Results: One hundred and one patients were included in the study. The mean age was 67.5 years and the cutaneous ADRs occurred in more women (65%) than men (35%). Etoricoxib was the most common suspected drug. Single and multiple NSAIDs reactors were identified in 91.1% and 8.9%, respectively. Angioedema with and without urticaria was the most common cutaneous ADRs in the elderly (39.6%) followed by maculopapular rash (18.8%). Forty one patients (40.6%) were categorized as serious ADRs. Almost all of the patients who developed serious reactions (97.5%) were diagnosed as angioedema with or without urticaria including anaphylaxis. Conclusion: Age-related pharmacokinetics alteration may predispose to severe ADRs from NSAIDs. This study could promote rational drug used and awareness of NSAIDs-induced ADRs in elderly patients.
American history encompasses a wide spectrum of dermatologic pathology that has affected past Presidents of the United States and their families. America’s founding father, George Washington, developed a ‘‘malignant carbuncle’’ on his left hip during his first year as president, requiring incision and drainage. James Madison developed frostbite on his nose after campaigning outside for the First Congress in 1788. A few days after delivering the Gettysburg Address, Abraham Lincoln developed ‘‘dusky red spots about the forehead,’’ which after spreading to his face and extremities, evolved into an acneiform appearance, coinciding with a smallpox epidemic. One of America’s Civil War heroes, Ulysses Grant, developed a cancerous growth at the base of his tongue in 1884; this occurred after many years of heavy drinking and smoking, inevitably leading to his unfavorable demise. Similarly, Grover Cleveland developed a malignancy on the left side of his jaw, involving the soft palate, and underwent a secret operation for its removal in 1893. In 1892, Rutherford B. Hayes developed dermatitis, involving his hands and face secondary to his exposure to poison ivy while pruning trees. Franklin D. Roosevelt’s pigmented nevus, located above his left eyebrow, no longer appeared in photographs after 1943, leading people to believe that it had been removed. The importance of this subtlety was noted after the president’s fatal seizure in 1945, raising questions regarding melanoma as the possible culprit. John F. Kennedy was diagnosed with Addison’s disease in 1947, years before serving as president. Although Kennedy exuded vitality with his youthful, tanned-like appearance, the hyperpigmentation of his face was actually a manifestation of his autoimmune condition. Lyndon Johnson underwent a clandestine procedure in 1967 in order to remove a basal cell carcinoma from his left ankle. Similarly, Ronald Reagan had basal cell carcinomas removed both during, and in the years following his presidency; moreover, his daughter, Maureen Reagan, subsequently passed away due to systemic melanoma metastases. Finally, it is well known that Bill Clinton has long suffered from rosacea and additionally received treatment for actinic keratosis and basal cell carcinoma. As revealed throughout American history, dermatology can indeed have an impact on anyone’s life, including the lives of prominent political leaders.
Commercial support: None identified.
Commercial support: None identified.
Background: Elderly people are commonly prescribed with polypharmacy due to multiple medical conditions which are associated with the risks for drug hypersensitivity. In addition, pharmacodynamics and pharmacokinetics alterations, including decreasing hepatic drug clearance and the decline of renal function, are also capable of contributing to the particularly risk for adverse drug reactions (ADRs) in elderly. Nonsteroidal antiinflammatory drugs (NSAIDs) are one of the most commonly prescribed medications, and about half of NSAID prescriptions are for elderly patients. However, the clinical knowledge of NSAID-induced cutaneous ADRs in elderly is limited. Objective: The aim of this study was to determine the association between the patient histories, clinical course, and causative NSAIDs drugs which contributed to cutaneous ADRs in the elderly.
AB28
J AM ACAD DERMATOL
MAY 2016