![]() These observations indicate the high impact of extrinsic aging on cellular functions and the process of endogenous (bone) regeneration. These results were validated in an in vivo model of compromised bone healing, which demonstrated significant increase regeneration in aged animals following oral antioxidant administration. Conversely, reduction of oxidative stress levels in vitro markedly improved MSC function. Proteome analysis and further cellular investigations strongly suggest that serum from aged animals not only changes expression of proteins related to mitochondria, unfolded protein binding or involved in stress responses, it also significantly enhances intracellular reactive oxygen species production and leads to the accumulation of oxidatively damaged proteins. We demonstrate that culture of mesenchymal stromal cells (MSCs) in serum from aged Sprague–Dawley rats negatively affects their survival and differentiation ability. ![]() Here, we hypothesized that this decline is primarily due to cell non-autonomous (extrinsic) aging mediated by the systemic environment. ![]() Even tissues capable of complete regeneration, such as bone, show an age-related reduction in their healing capacity. ![]()
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