Methionine restriction improves renal insulin signalling in aged kidneys

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.