Metformin reduces ageing adipose senescence
| Autor: | Matthieu Mantecon, Michael Atlan, Claire Lagathu, Véronique Béréziat, Laura Pelletier, Roberta Foresti, Bruno Fève, Mireille Laforge, Martine Auclair, Jennifer Gorwood, Roberto Motterlini, Jacqueline Capeau |
|---|---|
| Přispěvatelé: | Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Endocrinologie, diabétologie et endocrinologie de la reproduction [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), HAL-SU, Gestionnaire, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN] |
| Rok vydání: | 2021 |
| Předmět: |
AMPK
Aging senescence Endocrinology Diabetes and Metabolism [SDV]Life Sciences [q-bio] Adipose tissue AMP-Activated Protein Kinases medicine.disease_cause chemistry.chemical_compound 0302 clinical medicine Endocrinology Adipocyte Adipocytes oxidative stress Biology (General) Cells Cultured Cellular Senescence 0303 health sciences General Neuroscience General Medicine Middle Aged Metformin Mitochondria [SDV] Life Sciences [q-bio] Adipose Tissue Adipogenesis Medicine Female medicine.drug Research Article Human Senescence medicine.medical_specialty Stromal cell QH301-705.5 Science adipose stromal cells General Biochemistry Genetics and Molecular Biology adipogenesis 03 medical and health sciences Young Adult Insulin resistance Internal medicine medicine Humans Hypoglycemic Agents 030304 developmental biology General Immunology and Microbiology business.industry Cell Biology medicine.disease chemistry Ageing Stromal Cells business Mitochondrial dysfunction 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | eLife eLife, Vol 10 (2021) eLife, eLife Sciences Publication, 2021, 10, ⟨10.7554/eLife.62635⟩ eLife, 2021, 10, ⟨10.7554/eLife.62635⟩ |
| ISSN: | 1759-5037 2050-084X |
| Popis: | Aging is associated with central fat redistribution and insulin resistance. To identify age-related adipose features, we evaluated the senescence and adipogenic potential of adipose-derived stromal cells (ASCs) from abdominal subcutaneous fat obtained from healthy normal-weight young (60 years). Increased cell passages of young-donor ASCs (in vitro aging) resulted in senescence but not oxidative stress. ASC-derived adipocytes presented impaired adipogenesis but no early mitochondrial dysfunction. Conversely, aged-donor ASCs at early passages displayed oxidative stress and mild senescence. ASC-derived adipocytes exhibited oxidative stress, and early mitochondrial dysfunction but adipogenesis was preserved. In vitro aging of aged-donor ASCs resulted in further increased senescence, mitochondrial dysfunction, oxidative stress, and severe adipocyte dysfunction. When in vitro aged young-donor ASCs were treated with metformin, no alteration was alleviated. Conversely, metformin treatment of aged-donor ASCs decreased oxidative stress and mitochondrial dysfunction resulting in decreased senescence. Metformin’s prevention of oxidative stress and of the resulting senescence improved the cells’ adipogenic capacity and insulin sensitivity. This effect was mediated by the activation of AMP-activated protein kinase as revealed by its specific inhibition and activation. Overall, aging ASC-derived adipocytes presented impaired adipogenesis and insulin sensitivity. Targeting stress-induced senescence of ASCs with metformin may improve age-related adipose tissue dysfunction. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink