Low-dose pesticide mixture induces accelerated mesenchymal stem cells aging.

The general population is chronically exposed to multiple environmental contaminants such as pesticides. We have previously demonstrated that human mesenchymal stem cells (MSC) exposed in vitro to low doses of a mixture of seven common pesticides showed a permanent phenotype modification with a specific induction of an oxidative stress-related senescence. Pesticide mixture also induced a shift in MSC differentiation towards adipogenesis. We thus hypothesized that common combination of pesticides may induce a premature aging of adult MSC.Our goal was to evaluate if the prolonged exposure to pesticide mixture could accelerate aging-related markers and in particular deteriorate the immunosuppressive properties of MSCs.MSC exposed to pesticide mixture, under long-term culture and obtained from aging donor were compared by bulk RNA sequencing analysis. Aging, senescence and immunomodulatory markers were compared. A functional profile modified were found with similarities with aging process.