Proteomic and biological analysis of metformin senomorphics effects on the mesenchymal stromal cells

ABSTRACT: Senotherapeutics are new drugs, which can modulate senescence phenomena within tissues and reduces the onset of age-related pathologies. Senotherapeutics are divided in senolytics and senomorphics. The senolytics kill selectively senescent cells, while the senomorphics may delay or block the onset of senescence. Metformin is used for treatment of diabetes since several decades. Recently, it has been evidenced that metformin may have anti-aging properties by preventing DNA damage and inflammation. We evaluated the senomorphics effect of metformin on the biology human adipose mesenchymal stromal cells (MSCs) treated for six weeks with therapeutic doses of metformin. The study was combined with proteome analysis of changes occurring in MSCs intracellular and secretome protein composition, this to identify molecular pathways associated with the observed biological phenomena. The metformin reduced the replicative senescence and cell death phenomena, which are associated with prolonged in vitro cultivation. The continuous metformin supplementation delayed/reduced the impairment of MSC functions as evidenced by the presence of specific pathways in metformin treated samples: i) the alpha-adrenergic signaling, which contributes to regulation of MSCs physiological secretory activity; the signaling pathway associated with MSCs detoxification activity; the aspartate degradation pathway for optimal energy production. The senomorphics function of metformin seemed related to its reactive oxygen species (ROS) scavenging activity. In metformin treated samples, the CEBPA, TP53 and USF1 transcription factors appeared implicated in the regulation of several factors (SOD1, SOD2, CAT, GLRX, GSTP1) involved in blocking ROS.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Stem Cell

SUBMITTER: Servet ÖZCAN  

LAB HEAD: Servet Özcan

PROVIDER: PXD028349 | Pride | 2022-02-15

REPOSITORIES: Pride