Sepsis survivors suffer from additional morbidities, including higher disk 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; the
sepsis group received 15 mg/kg of bacterial
lipopolysaccharide i.p. After 48 hours, animals were sacrificed 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 days later in those patients who developed
sepsis. Telomere length was measured by quantitative PCR. Since oxidative stress is a known inducer of telomere shortening,
thiobarbituric acid reactive substances and
superoxide dismutase (SOD) activity were analyzed in order to evaluate oxidative stress burden. Induction of
endotoxemia in mice resulted in significant telomere shortening in spleen and kidney. Blood cells from patients that 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.