Sepsis induces telomere shortening: A potential mechanism responsible for delayed pathophysiological events in sepsis survivors?

Abstract

Sepsis survivors suffer from additional morbidities, including higher risk of readmissions, nervous system disturbances and cognitive dysfunction, and increased mortality, even several years after the initial episode of sepsis. In many ways, the phenotype of sepsis survivors resembles the phenotype associated with accelerated aging. Since telomere shortening is a hallmark of aging, we investigated whether sepsis also leads to telomere shortening. Male balb/c mice were divided into two groups: the control group received 100 μl of normal saline intraperitoneally (i.p.) and the sepsis group received 15 mg/kg of bacterial lipopolysac-charide i.p. After 48 h, animals were euthanized to collect blood, spleen and kidney. The human component of our study utilized blood samples obtained from patients in the trauma department and samples collected 7 d later in those patients who developed sepsis. Telomere length was measured by quantitative polymerase chain reaction. Since oxidative stress is a known inducer of telomere shortening, thiobarbituric acid-reactive substances and superoxide dismutase activity were analyzed to evaluate oxidative stress burden. Induction of endotoxemia in mice resulted in significant telomere shortening in spleen and kidney. Blood cells from patients who progressed to sepsis also exhibited a statistically significant reduction of telomere length. Endotoxemia in mice also induced an early-onset increase in oxidative stress markers but was not associated with a downregulation of telomerase protein expression. We conclude that endotoxemia and sepsis induce telomere shortening in various tissues and hypothesize that this may contribute to the pathogenesis of the delayed pathophysiological events in sepsis survivors.