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 yea...
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eLife Sciences Publications Ltd
2021
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oai:doaj.org-article:6426a1846c5b47f480f27f4a3ce2239c2021-11-24T12:27:20ZMetformin alleviates stress-induced cellular senescence of aging human adipose stromal cells and the ensuing adipocyte dysfunction10.7554/eLife.626352050-084Xe62635https://doaj.org/article/6426a1846c5b47f480f27f4a3ce2239c2021-09-01T00:00:00Zhttps://elifesciences.org/articles/62635https://doaj.org/toc/2050-084XAging 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.Laura Le PelletierMatthieu ManteconJennifer GorwoodMartine AuclairRoberta ForestiRoberto MotterliniMireille LaforgeMichael AtlanBruno FèveJacqueline CapeauClaire LagathuVeronique BereziateLife Sciences Publications Ltdarticlesenescenceadipose stromal cellsadipogenesisoxidative stressmetforminAMPKMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
senescence adipose stromal cells adipogenesis oxidative stress metformin AMPK Medicine R Science Q Biology (General) QH301-705.5 |
| spellingShingle |
senescence adipose stromal cells adipogenesis oxidative stress metformin AMPK Medicine R Science Q Biology (General) QH301-705.5 Laura Le Pelletier Matthieu Mantecon Jennifer Gorwood Martine Auclair Roberta Foresti Roberto Motterlini Mireille Laforge Michael Atlan Bruno Fève Jacqueline Capeau Claire Lagathu Veronique Bereziat Metformin alleviates stress-induced cellular senescence of aging human adipose stromal cells and the ensuing adipocyte dysfunction |
| 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. |
| format |
article |
| author |
Laura Le Pelletier Matthieu Mantecon Jennifer Gorwood Martine Auclair Roberta Foresti Roberto Motterlini Mireille Laforge Michael Atlan Bruno Fève Jacqueline Capeau Claire Lagathu Veronique Bereziat |
| author_facet |
Laura Le Pelletier Matthieu Mantecon Jennifer Gorwood Martine Auclair Roberta Foresti Roberto Motterlini Mireille Laforge Michael Atlan Bruno Fève Jacqueline Capeau Claire Lagathu Veronique Bereziat |
| author_sort |
Laura Le Pelletier |
| title |
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_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_sort |
metformin alleviates stress-induced cellular senescence of aging human adipose stromal cells and the ensuing adipocyte dysfunction |
| publisher |
eLife Sciences Publications Ltd |
| publishDate |
2021 |
| url |
https://doaj.org/article/6426a1846c5b47f480f27f4a3ce2239c |
| work_keys_str_mv |
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