Changes in noradrenaline- and serotonin-dependent intracellular signaling in senescent multipotent mesenchymal stromal cells

In this work, we studied how hormonal regulation of human adipose tissue stem cells changes during aging and how changes in hormonal regulation are associated with adipogenic differentiation of these cells. Postnatal adipose tissue stem cells — multipotent mesenchymal stromal cells (MSCs), were used as an object for studying hormonal regulation. We showed that both MSCs with induced replicative senescence and MSCs obtained from elderly donors have a reduced adipogenic potential. These cells have impaired mechanisms of regulation of adipogenic differentiation under noradrenaline and serotonin. The study of intracellular signaling cascades allowed us to establish that during senescence, MSCs exhibit reduced activation of both cAMP-dependent and phosphoinositide/calcium-dependent signaling cascades. Moreover, calcium responses to the addition of these hormones were delayed in time in MSCs with induced replicative aging. Thus, senescence leads to a decrease in the regulatory effect of hormones on the adipogenic differentiation of human MSCs.

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