Editors' ChoiceSepsis

Evading sepsis with exercise

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Science Translational Medicine  23 Aug 2017:
Vol. 9, Issue 404, eaao4211
DOI: 10.1126/scitranslmed.aao4211

Abstract

Aged mice preconditioned with a running routine were resistant to acute systemic sepsis compared with non-runner.

Young animals are often used in experimental biomedical studies examining diseases, medical procedures, and/or health complications normally associated with elderly patients, due to decreases in cost, biological variability, and time to publish when using young versus older animals. However, there are limitations to this approach, such as the research findings not being reproducible in older animals and ultimately not translatable for use in the clinic on elderly patients. Sepsis and systemic inflammation are examples of medical complications that have their highest prevalence in older patients, yet are often studied in younger animals. Previous works have shown survival in old rodents is greatly decreased compared with young rodents when given similar sepsis inducing procedures. Thus, research into the pathological intricacies of sepsis specific for the aged, and interventions to prevent or treat it, are needed.

In the recent study by Tyml et al., older mice equivalent in age to 65-year old humans were used to study both the pathophysiology of sepsis as well as its prevention through voluntary running exercise. They found increased systemic inflammatory marker myeloperoxidase in the lung and liver of these old mice when compared with historical data obtained from young mice. When given free and voluntary access to a running wheel for 2 months prior to the induction of sepsis, these old mice impressively ran an average of 7.5 km/day. This exercise preconditioning protected against sepsis induced acute inflammation, as determined by lessened myeloperoxidase, interleukin 6, and keratinocyte chemoattractant levels and decreased neutrophil infiltration in the lung and/or liver 7 hours post fecal injection. Additionally, sepsis-induced procoagulant responses were diminished in the running group, likely due to enhanced endothelial nitric oxide synthase expression in this group. In summary, the authors show that even at advanced ages, running exercise is effective as a preconditioning regimen against the development of sepsis-induced systemic inflammation and coagulation. Translating these findings in the clinic will require the development of a safe and effective exercise routine to be implemented in elderly populations.

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