RT Journal Article
SR Electronic
T1 Metformin alleviates aging-associated cellular senescence of human adipose stem cells and derived adipocytes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.05.326546
DO 10.1101/2020.10.05.326546
A1 Mantecon, Matthieu
A1 Le Pelletier, Laura
A1 Gorwood, Jennifer
A1 Auclair, Martine
A1 Atlan, Michael
A1 Fève, Bruno
A1 Capeau, Jacqueline
A1 Lagathu, Claire
A1 Béréziat, Véronique
YR 2020
UL http://biorxiv.org/content/early/2020/10/06/2020.10.05.326546.abstract
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.