Abstract: TH-PO954
Mary1 Increases Adenosine Triphosphate and Decreases Collagen-1 in Renal Cortices of Aged Mice
Session Information
- Geriatric Nephrology: Innovations and Insights
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Geriatric Nephrology
- 1300 Geriatric Nephrology
Authors
- Mcalister, Kai W., The University of Arizona College of Pharmacy, Tucson, Arizona, United States
- Janda, Jaroslav, The University of Arizona College of Pharmacy, Tucson, Arizona, United States
- Victor Santiago Raj, Paul, The University of Arizona College of Pharmacy, Tucson, Arizona, United States
- Thompson, Austin D., The University of Arizona College of Pharmacy, Tucson, Arizona, United States
- Schnellmann, Rick G., The University of Arizona College of Pharmacy, Tucson, Arizona, United States
Background
Kidney disease remains a leading cause of death in the United States and its prevalence is on the rise. One of the greatest risk factors for the development of kidney disease is aging. Unfortunately, little is known regarding prevention of the debilitating effects of renal aging.
Renal aging is characterized by increased mitochondrial dysfunction and fibrogenic mediators, which have been linked to various metabolic and renal impairments, such as diabetes, obesity, cardiovascular disease, and chronic inflammation.
Mary1 is an experimental therapeutic that induces mitochondrial biogenesis (MB) and restores renal function in a mouse model of AKI. We hypothesized that treatment with Mary1 may decrease markers of renal dysfunction during aging.
Methods
Mice were divided into three groups: 1) young (10-week-old) mice treated with vehicle control [saline + 0.1% DMSO], 2) aged (25-month-old) mice treated with vehicle control, and 3) aged mice treated with Mary1 [0.3 mg/kg] (n=6-8/group). Each group was further divided into subgroups and treated for 1) 3 weeks or 2) 16 weeks. Following treatment, kidneys were harvested, and cortical tissue was used for immunoblotting and RT-PCR.
Results
For the 3-week treatment group, Mary1-treated aged mice exhibited a 35% reduction in renal cortical collagen-1 mRNA, and a 61% reduction in collagen-1 protein compared to vehicle-treated aged mice. For the 16-week group, Mary1-treated aged mice exhibited a 46% reduction in renal cortical collagen-1 mRNA, and a 35% reduction in collagen-1 protein compared to vehicle-treated aged mice.
Additionally, Mary1 treatment increased renal cortical ATP by 73% compared to aged mice that received vehicle, reaching levels comparable to that in young mice in the 3-week treatment group. While Mary1-treated aged mice exhibited a 33% increase in renal cortical collagen-1 mRNA, there was a persistent 35% reduction in collagen-1 protein compared to vehicle-treated aged mice in the 16-week group.
Conclusion
These results show the therapeutic potential of Mary1 in ameliorating age-related renal cortical mitochondrial dysfunction and fibrosis. Further research is needed to determine the mechanism by which Mary1 achieves these therapeutic effects.
Funding
- Veterans Affairs Support