Oliver Dreesen's talk was not recorded.
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Sophie BELLANGER
Nicotinamide: how to kill two birds with one stone and modulate skin ageing |
Abstract
Nicotinamide (NAM, aka niacinamide or Vitamin B3) is a NAD+ precursor that shows anti-aging effects on skin. It maintains epidermal homeostasis, improves barrier function and reduces fine wrinkles. However, when we started our studies, the underlying biochemical mechanisms were unclear. Therefore, we investigated the effects of NAM in both normal and photoaging conditions, focusing on human primary keratinocyte phenotypes and mechanistic pathways. In 3D organotypic skin models cultured in standard conditions, NAM inhibits differentiation of the upper epidermal layers while maintaining proliferation at the basal layer. In 2D culture, this is characterized by lower expression of early (keratins 10 and 13) and late (involucrin and filaggrin) epidermal differentiation markers, better proliferation, elevated clonogenicity and an increased proportion of keratinocyte stem cells. Regarding photoaging, UVB radiation and oxidative stress induce dose-dependent premature terminal differentiation and senescence of human primary keratinocytes, as well as inflammation. In 3D organotypics, the phenotype is characterized by thickening of the granular layer, but thinning of the epidermis overall. NAM limited premature differentiation, ameliorated senescence (as evidenced by the maintenance of lamin B1 levels) and reduces secretion of IL-6 and IL-8. Last but not least, our mechanistic studies pinpoint enhancement of DNA repair and maintenance of energy metabolism as two crucial mechanisms mediating the beneficial effects of NAM against (photo)aging.
Nicotinamide (NAM, aka niacinamide or Vitamin B3) is a NAD+ precursor that shows anti-aging effects on skin. It maintains epidermal homeostasis, improves barrier function and reduces fine wrinkles. However, when we started our studies, the underlying biochemical mechanisms were unclear. Therefore, we investigated the effects of NAM in both normal and photoaging conditions, focusing on human primary keratinocyte phenotypes and mechanistic pathways. In 3D organotypic skin models cultured in standard conditions, NAM inhibits differentiation of the upper epidermal layers while maintaining proliferation at the basal layer. In 2D culture, this is characterized by lower expression of early (keratins 10 and 13) and late (involucrin and filaggrin) epidermal differentiation markers, better proliferation, elevated clonogenicity and an increased proportion of keratinocyte stem cells. Regarding photoaging, UVB radiation and oxidative stress induce dose-dependent premature terminal differentiation and senescence of human primary keratinocytes, as well as inflammation. In 3D organotypics, the phenotype is characterized by thickening of the granular layer, but thinning of the epidermis overall. NAM limited premature differentiation, ameliorated senescence (as evidenced by the maintenance of lamin B1 levels) and reduces secretion of IL-6 and IL-8. Last but not least, our mechanistic studies pinpoint enhancement of DNA repair and maintenance of energy metabolism as two crucial mechanisms mediating the beneficial effects of NAM against (photo)aging.
Bio
Sophie Bellanger obtained her Ph.D. in 2004 from the Pasteur Institute, France. She discovered that the Human Papillomavirus (HPV) E2 protein, hitherto considered a viral tumor suppressor, induces chromosomal instability and participates in the oncogenic potential of HPV. She then moved to the Pierre and Marie Curie University to investigate the roles of B-type cyclins in re-replication control. She joined the Institute of Medical Biology in 2006 as a Research Fellow, where she later led HPV projects related to cell cycle checkpoints, metabolism and apoptosis. In 2013, she was appointed as an independent Project Leader to work on skin stem cells. She is now a Principal Investigator in A*SRL, where her team studies the pathways that regulate human primary keratinocyte proliferation, differentiation and senescence in 2D culture and 3D organotypic skin models. Her main areas of investigation are keratinocyte stem cells, (photo)aging and mechanisms of action of anti-aging molecules ranging from cell cycle and metabolism chemical/protein regulators to nutraceuticals.
Sophie Bellanger obtained her Ph.D. in 2004 from the Pasteur Institute, France. She discovered that the Human Papillomavirus (HPV) E2 protein, hitherto considered a viral tumor suppressor, induces chromosomal instability and participates in the oncogenic potential of HPV. She then moved to the Pierre and Marie Curie University to investigate the roles of B-type cyclins in re-replication control. She joined the Institute of Medical Biology in 2006 as a Research Fellow, where she later led HPV projects related to cell cycle checkpoints, metabolism and apoptosis. In 2013, she was appointed as an independent Project Leader to work on skin stem cells. She is now a Principal Investigator in A*SRL, where her team studies the pathways that regulate human primary keratinocyte proliferation, differentiation and senescence in 2D culture and 3D organotypic skin models. Her main areas of investigation are keratinocyte stem cells, (photo)aging and mechanisms of action of anti-aging molecules ranging from cell cycle and metabolism chemical/protein regulators to nutraceuticals.
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Oliver Dreesen
Cellular Senescence & Skin Ageing |
Abstract
Ageing is an inevitable consequence of life and the major risk factor for the development of chronic medical conditions, such as cardiovascular and neurodegenerative diseases and cancer. Cellular senescence is one of the most fundamental processes that determine cellular ageing in vitro and in vivo. Senescent cells are terminally growth arrested cells that can no longer contribute to tissue repair or regeneration. In addition, they secrete a multitude of factors that promote tissue inflammation and deterioration. Senescent cells accumulate with age in many tissues, at sites of pre-neoplastic lesions or age-related pathologies, such as impaired heart regeneration and in ageing skin. Removal of senescent cells (by genetic ablation or pharmacological intervention) alleviates age-associated conditions. However, a significant challenge has been the identification of biomarkers that facilitate the unequivocal detection and quantification of senescent cells, particularly in complex tissues in vivo. By studying cells from patients with premature aging syndromes, my laboratory identified downregulation of lamin B1 - an intermediate filament protein and structural component of the nuclear envelope - as a novel biomarker to detect senescent cells. In this talk, I will outline the characterization of lamin B1 as a senescence biomarker and highlight its utility in understanding how environmental conditions, such as UV-B exposure, or certain anti-aging interventions, may accelerate or prevent senescence and skin aging, respectively.
Ageing is an inevitable consequence of life and the major risk factor for the development of chronic medical conditions, such as cardiovascular and neurodegenerative diseases and cancer. Cellular senescence is one of the most fundamental processes that determine cellular ageing in vitro and in vivo. Senescent cells are terminally growth arrested cells that can no longer contribute to tissue repair or regeneration. In addition, they secrete a multitude of factors that promote tissue inflammation and deterioration. Senescent cells accumulate with age in many tissues, at sites of pre-neoplastic lesions or age-related pathologies, such as impaired heart regeneration and in ageing skin. Removal of senescent cells (by genetic ablation or pharmacological intervention) alleviates age-associated conditions. However, a significant challenge has been the identification of biomarkers that facilitate the unequivocal detection and quantification of senescent cells, particularly in complex tissues in vivo. By studying cells from patients with premature aging syndromes, my laboratory identified downregulation of lamin B1 - an intermediate filament protein and structural component of the nuclear envelope - as a novel biomarker to detect senescent cells. In this talk, I will outline the characterization of lamin B1 as a senescence biomarker and highlight its utility in understanding how environmental conditions, such as UV-B exposure, or certain anti-aging interventions, may accelerate or prevent senescence and skin aging, respectively.
Bio
After completing his undergraduate degree in Bern, Switzerland, Oliver Dreesen worked at the Pasteur Institute in Paris, the University of California, San Diego, and Lonza AG in Switzerland. He received his Ph.D. from the Rockefeller University in New York City, where he studied the structure and function of telomeres and telomerase in the protozoan parasite Trypanosoma brucei. In 2009, he joined the Institute of Medical Biology in Singapore to study telomeres during cellular reprogramming and in human genetic diseases. Dreesen was promoted to Project Leader in 2013, and to Principal Investigator and Head of the Laboratory for Cell Ageing in 2016. His team at the A*STAR Skin Research Labs (ASRL) investigates how perturbations at the nuclear lamina affect cell physiology and result in premature cellular senescence, human skin ageing and disease. He served as President of the Skin Research Society Singapore from 2019-2021
After completing his undergraduate degree in Bern, Switzerland, Oliver Dreesen worked at the Pasteur Institute in Paris, the University of California, San Diego, and Lonza AG in Switzerland. He received his Ph.D. from the Rockefeller University in New York City, where he studied the structure and function of telomeres and telomerase in the protozoan parasite Trypanosoma brucei. In 2009, he joined the Institute of Medical Biology in Singapore to study telomeres during cellular reprogramming and in human genetic diseases. Dreesen was promoted to Project Leader in 2013, and to Principal Investigator and Head of the Laboratory for Cell Ageing in 2016. His team at the A*STAR Skin Research Labs (ASRL) investigates how perturbations at the nuclear lamina affect cell physiology and result in premature cellular senescence, human skin ageing and disease. He served as President of the Skin Research Society Singapore from 2019-2021
Chairs
Srikala Raghavan, ASRL
Aishwarya Sridharan, ASRL
Srikala Raghavan, ASRL
Aishwarya Sridharan, ASRL