Infection and smoking are associated with decreased plasma concentration of the anti-aging protein, α-klotho^a

Abstract

Objective The objective of this study was to determine whether maternal plasma concentrations of soluble α-klotho are different between women with microbial invasion of the intra-amniotic cavity (MIAC) and those without MIAC among preterm labor and intact membranes (PTL) or preterm prelabor rupture of membranes (pPROM). Methods A cross-sectional study was conducted to include women in the following groups:1) PTL with MIAC (n=14); 2) PTL without MIAC (n=79); 3) pPROM with MIAC (n=30); and 4) pPROM without MIAC (n=33). MIAC was defined as a positive amniotic fluid culture for microorganisms (aerobic/anaerobic bacteria or genital mycoplasmas). Amniotic fluid samples were obtained within 48 hours from maternal blood collection. Plasma concentration of soluble α-klotho was determined by ELISA. Results 1) The median plasma concentration (pg/mL) of soluble α-klotho was significantly lower in patients with MIAC than in those without MIAC (787.0 vs. 1117.8; p <0.001); 2) Among patients with PTL, those with MIAC had a lower median plasma concentration (pg/mL) of soluble α-klotho than those without MIAC (787.0 vs. 1138.9; p=0.007); 3) Among patients with pPROM, those with MIAC had a lower median plasma concentration (pg/mL) of soluble α-klotho than those without MIAC (766.4 vs. 1001.6; p=0.045); 4) There was no significant difference in the median plasma concentration of soluble α-klotho between PPROM without MIAC and PTL without MIAC (1001.6 pg/mL vs. 1138.9 pg/mL, respectively; p=0.5); 5) After adjustment for potential confounders (maternal age, tobacco use, gestational age at venipuncture), soluble α-klotho remained significantly associated with MIAC (p= 0.02); and 6) Among patients without MIAC, smoking was significantly associated with a lower median plasma concentration soluble α-klotho than in non-smokers (794.2 pg/mL vs. 1382.0 pg/mL, respectively; p<0.001); however, this difference was not observed in patients with MIAC. Conclusions Intra-amniotic infection occurring at preterm gestations (regardless of membrane status) was associated with a decrease in maternal plasma concentrations of soluble α-klotho. Moreover, among patients without infection, the plasma concentration of soluble α-klotho was lower in smokers.

Soluble extracellular Klotho decreases sensitivity to cigarette smoke induced cell death in human lung epithelial cells

“…The authors correctly indicate that loss of KL expression due to age or disease may contribute to disease progression and loss of homeostatic functions. Interestingly, a recent study has identified a significant decrease in soluble KL levels in sera of smokers compared to non-smokers 51 . If the expression of KL decreases due to age and CS exposure, circulating KL would be significantly reduced in the lungs of susceptible COPD patients.…”

Chronic nicotine exposure reduces klotho expression and triggers different renal and hemodynamic responses inklotho-haploinsufficient mice

“…To our knowledge, this is the first time that nicotine exposure has been related to Klotho expression, although such an association has been postulated. Lam-Rachlin et al (14) demonstrated that, among pregnant women without microbial invasion of the amniotic cavity, the smokers had lower plasma levels of Klotho than did the nonsmokers. In patients with chronic obstructive pulmonary disease, smoking has been shown to induce an increase in the plasma levels of FGF23, without the expected corresponding decrease in phosphate levels, suggesting FGF23 resistance (25).…”

Neonatology oxidative status in preterm infants with premature preterm rupture of membranes and fetal inflammatuar response syndrome

“…Our result supports the thesis that oxidative stress is responsible for the premature aging of the fetal membranes, especially in PPROM occuring before 34 weeks of gestation. 13,14,26,27 The number of studies investigating whether FIRS is accompanied by oxidative stress is insufficient. A majority of the previous studies evaluated the relationship of histologic chorioamnionitis and microbial invasion of amniotic cavitiy (MIAC) with oxidative stress.…”