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Aging kidney is associated with metabolic rewiring and epigenetic reprogramming
Pragney Deme1, Rhea Bhargava2, Heddwen L Brooks1
1Department of Physiology, Tulane University School of Medicine, 1430 Tulane Ave, New Orleans, LA, 70112, USA.
Geroscience
|January 7, 2026
Summary
Aging kidneys show altered metabolism and increased epimetabolites, impacting renal physiology. These changes are sex-specific, revealing a complex interplay between aging, metabolism, and epigenetics in kidney function.
Area of Science:
- Renal Physiology
- Metabolomics
- Epigenetics
- Aging Biology
Background:
- Renal aging involves complex metabolic and epigenetic changes.
- Sex-specific differences in aging renal disease are known but poorly understood.
- The intersection of renal metabolism, epigenetics, and aging requires further investigation.
Purpose of the Study:
- To investigate age- and sex-specific alterations in renal metabolic pathways.
- To examine the impact of aging on metabolite cofactors of epigenetic modifiers in the kidney.
- To elucidate the interplay between renal metabolomics and epigenetics during aging.
Main Methods:
- Kidney homogenates from young and aged sex-matched mice were analyzed using High-Performance Liquid Chromatography-Triple Time-of-Flight (HPLC-TripleTOF) liquid chromatography-mass spectrometry (LC-MS).
- Metabolite levels, including epimetabolites and epigenetic cofactor metabolites, were quantified.
- Sex-specific metabolic pathway analyses were performed.
Main Results:
- Aging kidneys exhibited increased glycolysis, reduced fatty acid oxidation, mitochondrial dysfunction, oxidative stress, and impaired waste clearance.
- Elevated levels of methylated and acetylated intermediate metabolites (epimetabolites) were observed in aged mice.
- Key epigenetic cofactor metabolites (acetyl-CoA, FAD, α-ketoglutarate) showed age-related alterations.
- Aged female mice displayed enhanced amino acid/tryptophan metabolism and reduced ammonia clearance compared to aged males.
Conclusions:
- Aging induces significant metabolic reprogramming in the kidney, characterized by increased epimetabolites.
- Age-related metabolic changes in the kidney are sex-specific.
- These findings highlight a crucial link between renal metabolomics, epigenetics, and sex-specific aging processes.
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