Counteracting diabetes-induced adipose tissue derived-stromal cell senescence.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Adipose tissue stromal cells (ADSCs) are prone to functional decline and senescence during metabolic disturbances. In diabetes mellitus (DM), the pathogenic microenvironment induces oxidative stress causing ADSCs to senesce. The senescence associated secretory phenotype (SASP) in turn drives disease progression. The pathogenesis of DM is thus both a cause and consequence of senescence. Therapeutically preventing the onset of senescence in ADSCs may play a significant role in preventing disease progression and directly impact the onset of comorbidities. The purpose of this study was to establish an in vitro model that mimic the DM micro-environment to use as a screening tool to assess the therapeutic efficacy of preventative and restorative agents. Exposing ADSCs (<passage 10) to a combination of high glucose, advanced glycation end products (AGE-BSA) and TNFα in culture for a period of 3 days induced senescence in 70 ± 4 % of cells (β-galactosidase assay). This coincided with increased ROS production, DNA damage (yH2Ax foci) and excessive release of SASP factors (IFNγ, TNFα, IL1β, IL8, IL6). Pretreatment of ADSCs as well as early intervention using either Metformin (50 μg/mL) or ascorbic acid 2 phosphate (AAP 0.6 mM) could prevent the onset of premature senescence. The expression of genes related to cell cycle (p21 cip1 , p16 INK4A ), apoptosis (p53), inflammation (TNFα, IL6, P

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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