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Metformin alleviates stress-induced cellular senescence of aging human adipose stromal cells and the ensuing adipocyte dysfunction

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 (<25 years)...

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Autores principales: Le Pelletier, Laura, Mantecon, Matthieu, Gorwood, Jennifer, Auclair, Martine, Foresti, Roberta, Motterlini, Roberto, Laforge, Mireille, Atlan, Michael, Fève, Bruno, Capeau, Jacqueline, Lagathu, Claire, Bereziat, Veronique
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526089/
https://www.ncbi.nlm.nih.gov/pubmed/34544550
http://dx.doi.org/10.7554/eLife.62635
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author Le Pelletier, Laura
Mantecon, Matthieu
Gorwood, Jennifer
Auclair, Martine
Foresti, Roberta
Motterlini, Roberto
Laforge, Mireille
Atlan, Michael
Fève, Bruno
Capeau, Jacqueline
Lagathu, Claire
Bereziat, Veronique
author_facet Le Pelletier, Laura
Mantecon, Matthieu
Gorwood, Jennifer
Auclair, Martine
Foresti, Roberta
Motterlini, Roberto
Laforge, Mireille
Atlan, Michael
Fève, Bruno
Capeau, Jacqueline
Lagathu, Claire
Bereziat, Veronique
author_sort Le Pelletier, Laura
collection PubMed
description 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 (<25 years) or older women (>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.
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spelling pubmed-85260892021-10-21 Metformin alleviates stress-induced cellular senescence of aging human adipose stromal cells and the ensuing adipocyte dysfunction Le Pelletier, Laura Mantecon, Matthieu Gorwood, Jennifer Auclair, Martine Foresti, Roberta Motterlini, Roberto Laforge, Mireille Atlan, Michael Fève, Bruno Capeau, Jacqueline Lagathu, Claire Bereziat, Veronique eLife Cell Biology 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 (<25 years) or older women (>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. eLife Sciences Publications, Ltd 2021-09-21 /pmc/articles/PMC8526089/ /pubmed/34544550 http://dx.doi.org/10.7554/eLife.62635 Text en © 2021, Le Pelletier et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Le Pelletier, Laura
Mantecon, Matthieu
Gorwood, Jennifer
Auclair, Martine
Foresti, Roberta
Motterlini, Roberto
Laforge, Mireille
Atlan, Michael
Fève, Bruno
Capeau, Jacqueline
Lagathu, Claire
Bereziat, Veronique
Metformin alleviates stress-induced cellular senescence of aging human adipose stromal cells and the ensuing adipocyte dysfunction
title Metformin alleviates stress-induced cellular senescence of aging human adipose stromal cells and the ensuing adipocyte dysfunction
title_full Metformin alleviates stress-induced cellular senescence of aging human adipose stromal cells and the ensuing adipocyte dysfunction
title_fullStr Metformin alleviates stress-induced cellular senescence of aging human adipose stromal cells and the ensuing adipocyte dysfunction
title_full_unstemmed Metformin alleviates stress-induced cellular senescence of aging human adipose stromal cells and the ensuing adipocyte dysfunction
title_short Metformin alleviates stress-induced cellular senescence of aging human adipose stromal cells and the ensuing adipocyte dysfunction
title_sort metformin alleviates stress-induced cellular senescence of aging human adipose stromal cells and the ensuing adipocyte dysfunction
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526089/
https://www.ncbi.nlm.nih.gov/pubmed/34544550
http://dx.doi.org/10.7554/eLife.62635
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