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bioRxiv · 10.1101/2020.10.05.326546

Metformin alleviates aging-associated cellular senescence of human adipose stem cells and derived adipocytes

Mantecon, M.·Le Pelletier, L.·Gorwood, J.·Auclair, M.·Atlan, M.·Feve, B.·Capeau, J.·Lagathu, C.·Bereziat, V.
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Abstract

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-stemcells (ASCs) from abdominal subcutaneous fat obtained from healthy normal-weight young (<25y) or older women (>60y). Aged-donor ASCs showed more intense features of aging (senescence, mitochondrial dysfunction, and oxidative stress) than young-donor ASCs. Oxidative stress and mitochondrial dysfunction occurred earlier in adipocytes derived from aged-donor than from young-donor ASCs, leading to insulin resistance and impaired adipogenesis. When aged-donor ASCs were treated with metformin, senescence, oxidative stress and mitochondrial dysfunction returned to the levels observed in young-donor ASCs. Furthermore, metformins prevention of senescence and dysfunction during ASC proliferation restored the cells adipogenic capacity and insulin sensitivity. This effect was mediated by the activation of AMP-activated-protein-kinase. We show here that targeting senescent ASCs from aged women with metformin may alleviate age-related dysfunction, insulin resistance, and impaired adipogenesis.

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Mantecon, M., Le Pelletier, L., Gorwood, J., Auclair, M., Atlan, M., Feve, B., Capeau, J., Lagathu, C., Bereziat, V.. 2020-10-06. Metformin alleviates aging-associated cellular senescence of human adipose stem cells and derived adipocytes. https://doi.org/10.1101/2020.10.05.326546

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