title: Sepsis induces telomere shortening: a potential mechanism responsible for delayed pathophysiological events in sepsis survivors?
abstract: 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.
authors.affiliation: Departamento de Clínica Médica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: Naara Mendes
authors.initials: NM
authors.lastname: Oliveira
authors.affiliation: Departamento de Clínica Médica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil.|Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Ester C S
authors.initials: ECS
authors.lastname: Rios
authors.affiliation: Departamento de Clínica Médica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: Thais Martins
authors.initials: TM
authors.lastname: de Lima
authors.affiliation: Departamento de Clínica Médica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: Vanessa Jacob
authors.initials: VJ
authors.lastname: Victorino
authors.affiliation: Departamento de Clínica Médica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: Hermes
authors.initials: H
authors.lastname: Barbeiro
authors.affiliation: Departamento de Clínica Médica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: Fabiano
authors.initials: F
authors.lastname: Pinheiro da Silva
authors.affiliation: Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabo
authors.affiliation: Departamento de Clínica Médica, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: Francisco Garcia
authors.initials: FG
authors.lastname: Soriano
keywords: aging; endotoxemia; oxidative stress; sepsis; telomerase