Sepsis triggered by endotoxinemia may impair cardiac function. A decline in tolerance to septic shock occurs with aging. This study addressed the hypothesis that aging negatively impairs expression of gelsolin, and axerts the regulatory effects on the water channel protein aquaporin-1 (AQP-1) and endotoxin-inducible nitric oxide synthase (iNOS). We explored whether the age-related gene changes are associated with the cardiac dysfunction induced by endotoxic stress exposure. Male mice at young (3-month) and old (12-month) ages received intraperitoneal injections of saline or lipopolysaccharide (LPS, 30mg/Kg). Cardiac performance and morphology were analyzed by echocardiography at baseline and 2 and 24 h after injection. At the end of treatment, the animals were sacrificed, and cardiac tissues were collected for assessing expression of gelsolin, AQP-1, iNOS, and transcription-3 (STAT3). LPS administration led to a decreased contractility while increasing cardiac dimensions in both young and old mice. LPS also markedly induced expression of gelsolin in both animal groups. However, compared to young mice, old mice showed compromised induction of gelsolin and cardiac performance in response to endotoxin. Meanwhile, the LPS-exposed old animals exhibited higher levels of AQP-1, iNOS, and phosphorylated STAT3. Gelsolin-null mice had increased expression of glycosylated AQP-1 and STAT3 phosphorylation as well as cardiac dysfunction. Thus, endotoxin administration induces expression of gelsolin, AQP-1 and pro-inflammatory genes, such as iNOS. Our data suggest that changed expression of gelsolin, AQP-1 and iNOS may contribute to dysfunction of hearts in aged subjects with septic endotoxinemia.