PT  - JOURNAL ARTICLE
AU  - Mantecon, Matthieu
AU  - Le Pelletier, Laura
AU  - Gorwood, Jennifer
AU  - Auclair, Martine
AU  - Atlan, Michael
AU  - Fève, Bruno
AU  - Capeau, Jacqueline
AU  - Lagathu, Claire
AU  - Béréziat, Véronique
TI  - Metformin alleviates aging-associated cellular senescence of human adipose stem cells and derived adipocytes
AID  - 10.1101/2020.10.05.326546
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.10.05.326546
4099  - http://biorxiv.org/content/early/2020/10/06/2020.10.05.326546.short
4100  - http://biorxiv.org/content/early/2020/10/06/2020.10.05.326546.full
AB  - 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, metformin’s 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.