Kidney Week

Abstract: TH-PO0262

Male and Female Rats Display Divergent Renal Mitochondrial Bioenergetics in Aging

Session Information

• Hypertension and CVD: Mechanisms
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1601 Hypertension and CVD: Basic

Authors

• Schibalski, Ryan, Augusta University Medical College of Georgia, Augusta, Georgia, United States

Ryan Schibalski

• Spires, Denisha R., Augusta University Medical College of Georgia, Augusta, Georgia, United States

Denisha R. Spires, PhD

• Cherezova, Alena, Augusta University Medical College of Georgia, Augusta, Georgia, United States

Alena Cherezova, MS

• Jones, Adam C., Augusta University Medical College of Georgia, Augusta, Georgia, United States

Adam C. Jones

• Christopher, Courtney J., The University of Tennessee Knoxville Department of Chemistry, Knoxville, Tennessee, United States

Courtney J. Christopher

• Abais-Battad, Justine M., Augusta University Medical College of Georgia, Augusta, Georgia, United States

Justine M. Abais-Battad, PhD

• Campagna, Shawn R., The University of Tennessee Knoxville Department of Chemistry, Knoxville, Tennessee, United States

Shawn R. Campagna, PhD

• Ilatovskaya, Daria, Augusta University Medical College of Georgia, Augusta, Georgia, United States

Daria Ilatovskaya, MS, PhD

Background

Aging is associated with mitochondrial dysfunction and a decline in sex hormone levels. Females are generally protected from renal diseases until menopause; however, there is a gap in knowledge regarding the role of sex hormones in renal mitochondrial bioenergetics during aging. We hypothesized that testosterone and estrogen differentially regulate renal mitochondrial bioenergetics and metabolic pathways, with gonadectomies exacerbating mitochondrial dysfunction.

Methods

Male and female Sprague Dawley (SD) rats were assigned into groups (n=6-10/group), and gonadectomy or sham surgery was performed before 4 wks of age. At 3 and 12 months of age kidneys were perfused, and cortical tissues were collected for mitochondrial isolations. Spectrofluorimetry was used to measure mitochondrial membrane potential (ΔΨm) and H₂O₂ production using TMRM and Amplex Red. Metabolic profiles of renal cortices were generated using UHPLC-HRMS; metabolites were identified in El-MAVEN using exact mass and retention time with an in-house library. MetaboAnalyst 6.0 (cutoff fold change 1.1, p<0.05) and OriginPro were used for analysis (two-way ANOVA with Holm-Sidak).

Results

Renal mitochondrial ΔΨm displayed similar values at 3 months across all groups. At 12 months we report lower ΔΨm in males vs females (p<0.001); male gonadectomy increased ΔΨm (p=0.3). Cortical H₂O₂ was higher in females than in males at all timepoints (p<0.001), whereas ovariectomy lowered H₂O₂ at 12 months of age (p<0.001). Orchiectomy in males resulted in higher H₂O₂ production (p<0.001) at both ages. Metabolomics demonstrated divergent metabolic preferences at 3 months of age (females use TCA cycle, while males rely on the polyamine biosynthetic pathway; 55 metabolites were differentially abundant, including nucleotides/nucleosides and amino acid pathways). Gonadectomies reduced that number to 4 (AMP/dGMP, Riboflavin, Methionine Sulfoxide, FAD, p<0.05). At 12 months of age, there were 15 differently abundant metabolites in the shams, while only folate was different in the gonadectomized groups.

Conclusion

Our data established the impact of sex hormones on mitochondrial bioenergetics and will help elucidate sex-specific metabolism related targets that can mitigate the effects of aging on kidney function.

Funding

• Other NIH Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025mxh7wdbe