Impairment of Renal and Hematopoietic Stem/Progenitor Cell Compartments in Frailty Syndrome: Link With Oxidative Stress, Plasma Cytokine Profiles, and Nuclear DNA Damage.

Silvia Bombelli, Chiara Grasselli, Paolo Mazzola, Valentina Veronesi, Ivana Morabito, Nicola Zucchini, Chiara M Scollo, Salvatore I Blanco, Sofia De Marco, Barbara Torsello, Federica Vitarelli, Laura Antolini, Cristina Bianchi, Valerio Leoni, Giuseppe Bellelli, Roberto A Perego

School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy. · pubmed

Paper

Abstract

Frailty is an age-related syndrome that drives multiple physiological system impairments in some older adults, and its pathophysiological mechanisms remain unclear. We evaluated whether frailty-related biological processes could impair stem cell compartments, specifically the renal stem compartment, given that kidney dysfunctions are frequent in frailty. A well-characterized in vitro nephrosphere model of human adult renal stem/progenitor cells has been instrumental to and was appropriate for verifying this hypothesis in our current research. Evaluating the effects of plasma from older individuals with frailty (frail plasma) on allogeneic renal stem/progenitor cells, we showed significant functional impairment and nuclear DNA damage in the treated cells of the renal stem compartment. The analysis of the frail plasma revealed mitochondrial functional impairment associated with the activation of oxidative stress and a unique inflammatory mediator profile in frail individuals. In addition, the plasma of frail subjects also contained the highest percentage of DNA-damaged autologous circulating hematopoietic progenitor/stem cells. The integration of both molecular and functional data obtained allowed us to discern patterns associated with frailty status, irrespective of the comorbidities present in the frail individuals. The data obtained converged toward biological conditions that in frailty caused renal and hematopoietic impairment of stem cells, highlighting the possibility of concomitant exhaustion of several stem compartments.

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Research summary

The paper investigates the biological mechanisms underlying frailty, an age-related syndrome, and its impact on stem cell compartments, specifically in the context of oxidative stress and DNA damage. This focus on the root causes of frailty and its implications for stem cell function is relevant to longevity research. However, while the findings contribute to understanding frailty and its biological underpinnings, they represent solid research with limited immediate implications for broader longevity strategies, thus warranting a score of 4.

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