Purpose: Aging is a complex biological process that begins at the cellular level, disrupting energy homeostasis. This study investigated the role of Sirt3, major mitochondrial deacetylase involved in metabolic pathways, in sex-dependent changes in energy homeostasis during aging in kidney of Sirt3 WT and KO mice.

Methods: Enzymatic activity, lipid peroxidation, protein carbonylation with Western blot and metabolomic analyses were performed to assess physiological and metabolic parameters

Results: Higher Sirt3 expression in male WT mice leads to increased vulnerability to its deficiency, as reflected in the shorter lifespan of male KO mice. This is further supported by distinct metabolomic clustering in male KO mice, highlighting significant metabolic disruptions. Male-specific declines in metabolites such as creatine, phosphorylcholine, trimethylamine-N-oxide, and L-carnitine, along with reduced trifunctional multienzyme complex subunit β (HADHB) expression, point to impaired fatty acid metabolism and mitochondrial dysfunction.

Conclusions: The findings emphasize the sex-specific function of Sirt3 in regulating mitochondrial activity, energy metabolism, and oxidative stress in the murine kidney, with male mice exhibiting a greater reliance on Sirt3 for metabolic stability.

Purpose: This study aimed to investigate the association between paraoxonase 1 (PON1) activity phenotypes and redox status parameters, while evaluating the role of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) as a predictor of mortality and cardiovascular risk in patients undergoing chronic haemodialysis (HD).
Methods: This study cohort comprised patients with end-stage renal disease (ESRD). PON1 paraoxonase (POase) and arylesterase (ARE) activities, alongside a comprehensive redox profile, were determined spectrophotometrically. TNF-α concentrations were quantified via ELISA. PON1 phenotypes (QQ, QR, RR) were assigned using the POase/ARE ratio and the antimodal method. Survival analysis was performed using the Kaplan-Meier method.
Results: The RR phenotype was the most prevalent among HD patients (43.2%) and was significantly associated with the highest levels of oxidative stress, specifically elevated total oxidative status (TOS) and advanced oxidation protein products (AOPP) (p < 0.001). TNF-α concentrations were significantly higher in patients who died during the study compared to survivors (5.22 vs. 3.45 pg/mL, p = 0.050). Kaplan-Meier analysis confirmed that TNF-α levels > 5 pg/mL are a significant predictor of shorter survival (log-rank = 4.21, p = 0.040). Elevated TNF-α directly correlated with dyslipidemia progression and a higher atherosclerosis index.
Conclusions: The PON1 RR phenotype and elevated TNF-α concentrations (> 5 pg/mL) serve as critical biomarkers of oxidative and inflammatory status in HD patients. Their synergistic interaction contributes to accelerated atherogenesis and increased mortality, highlighting their utility in clinical risk stratification.