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

Mantecon, Matthieu; Pelletier, Laura; Gorwood, Jennifer; Auclair, Martine; Atlan, Michaël; Fève, Bruno; Capeau, Jacqueline; Lagathu, Claire; Béréziat, Véronique

doi:10.1101/2020.10.05.326546

Cited by 1 publication

(1 citation statement)

References 45 publications

(52 reference statements)

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“…In particular, the multiple inflammatory cytokines being induced and subsequently orchestrating (during) cellular senescence were known to be modulated by metformin treatment, as metformin was shown to inhibit (the NF-KκB-dependent) SASP [19]. Besides the favorable influence of metformin on oxidative stress and inflammation, metformin was even shown to alleviate the aging-associated cellular senescence [20].…”

Section: Introductionmentioning

confidence: 99%

Metformin Protects against Radiation-Induced Acute Effects by Limiting Senescence of Bronchial-Epithelial Cells

Hansel

Barr

Schemann

et al. 2021

IJMS

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Radiation-induced damage to normal lung parenchyma remains a dose-limiting factor in thorax-associated radiotherapy (RT). Severe early and late complications with lungs can increase the risk of morbidity in cancer patients after RT. Herein, senescence of lung epithelial cells following RT-induced cellular stress, or more precisely the respective altered secretory profile, the senescence-associated secretory phenotype (SASP), was suggested as a central process for the initiation and progression of pneumonitis and pulmonary fibrosis. We previously reported that abrogation of certain aspects of the secretome of senescent lung cells, in particular, signaling inhibition of the SASP-factor Ccl2/Mcp1 mediated radioprotection especially by limiting endothelial dysfunction. Here, we investigated the therapeutic potential of a combined metformin treatment to protect normal lung tissue from RT-induced senescence and associated lung injury using a preclinical mouse model of radiation-induced pneumopathy. Metformin treatment efficiently limited RT-induced senescence and SASP expression levels, thereby limiting vascular dysfunctions, namely increased vascular permeability associated with increased extravasation of circulating immune and tumor cells early after irradiation (acute effects). Complementary in vitro studies using normal lung epithelial cell lines confirmed the senescence-limiting effect of metformin following RT finally resulting in radioprotection, while fostering RT-induced cellular stress of cultured malignant epithelial cells accounting for radiosensitization. The radioprotective action of metformin for normal lung tissue without simultaneous protection or preferable radiosensitization of tumor tissue might increase tumor control probabilities and survival because higher radiation doses could be used.

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Section: Introductionmentioning

confidence: 99%