Methionine restriction improves renal insulin signalling in aged kidneys
Louise Grant1, Emma K Lees2, Laura A Forney3
1Institute of Medical Sciences, University of Aberdeen, College of Life Sciences and Medicine, Foresterhill Health Campus, Aberdeen, UK.
Abstract:
Dietary methionine restriction (MR) leads to loss of adiposity, improved insulin sensitivity and lifespan extension. The possibility that dietary MR can protect the kidney from age-associated deterioration has not been addressed. Aged (10-month old) male and female mice were placed on a MR (0.172% methionine) or control diet (0.86% methionine) for 8-weeks and blood glucose, renal insulin signalling, and gene expression were assessed. Methionine restriction lead to decreased blood glucose levels compared to control-fed mice, and enhanced insulin-stimulated phosphorylation of PKB/Akt and S6 in kidneys, indicative of improved glucose homeostasis. Increased expression of lipogenic genes and downregulation of PEPCK were observed, suggesting that kidneys from MR-fed animals are more insulin sensitive. Interestingly, renal gene expression of the mitochondrial uncoupling protein UCP1 was upregulated in MR-fed animals, as were the anti-ageing and renoprotective genes Sirt1, FGF21, klotho, and β-klotho. This was associated with alterations in renal histology trending towards reduced frequency of proximal tubule intersections containing vacuoles in mice that had been on dietary MR for 190days compared to control-fed mice, which exhibited a pre-diabetic status. Our results indicate that dietary MR may offer therapeutic potential in ameliorating the renal functional decline related to ageing and other disorders associated with metabolic dysfunction by enhancing renal insulin sensitivity and renoprotective gene expression.
Insights
Dietary methionine restriction in mice improved kidney function and insulin sensitivity, potentially protecting against age-related decline and metabolic dysfunction. This dietary change enhanced key protective genes and improved glucose homeostasis.
Area of Science:
- Gerontology
- Metabolic research
- Renal physiology
Background:
- Dietary methionine restriction (MR) is known to extend lifespan and improve metabolic health.
- The impact of MR on age-associated kidney deterioration remains unaddressed.
- Metabolic dysfunction contributes to kidney disease and aging.
Purpose of the Study:
- To investigate the effects of dietary methionine restriction on kidney function and insulin sensitivity in aging mice.
- To assess the potential renoprotective effects of MR against age-related kidney changes.
- To explore the molecular mechanisms underlying MR's impact on renal health.
Main Methods:
- Aged male and female mice were fed either a methionine-restricted (0.172% methionine) or control (0.86% methionine) diet for 8 weeks.
- Assessed blood glucose levels, renal insulin signaling pathways (PKB/Akt, S6 phosphorylation), and gene expression.
- Analyzed renal histology for age-related changes and evaluated expression of key metabolic, anti-aging, and renoprotective genes (UCP1, Sirt1, FGF21, klotho, β-klotho).
Main Results:
- Methionine restriction significantly decreased blood glucose levels and enhanced insulin signaling in the kidneys.
- MR increased the expression of lipogenic genes and decreased PEPCK, indicating improved renal insulin sensitivity.
- Upregulation of anti-aging and renoprotective genes (Sirt1, FGF21, klotho, β-klotho) and UCP1 was observed in MR-fed mice.
- Histological analysis showed a trend towards reduced kidney damage in MR-fed mice compared to controls, which exhibited pre-diabetic signs.
Conclusions:
- Dietary methionine restriction enhances renal insulin sensitivity and upregulates key renoprotective and anti-aging genes.
- MR may offer therapeutic potential for mitigating age-related kidney decline and metabolic dysfunction.
- These findings suggest MR could be a valuable strategy for preserving kidney function during aging.
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