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Published on: August 9, 2013
Dietary methionine restriction modulates renal response and attenuates kidney injury in mice
Diana Cooke1, Amadou Ouattara1, Gene P Ables1
1Orentreich Foundation for the Advancement of Science, Cold Spring, New York, USA.
Abstract:
Methionine restriction (MR) extends the lifespan across several species, such as rodents, fruit flies, roundworms, and yeast. MR studies have been conducted on various rodent organs, such as liver, adipose tissue, heart, bones, and skeletal muscle, to elucidate its benefits to the healthspan; however, studies of the direct effect of MR on kidneys are lacking. To investigate the renal effects of MR, we used young and aged unilateral nephrectomized and 5/6 nephrectomized (5/6Nx) mice. Our studies indicated that MR mice experienced polydipsia and polyuria compared with control-fed counterparts. Urine albumin, creatinine, albumin-to-creatinine ratio, sulfur amino acids, and electrolytes were reduced in MR mice. Kidneys of MR mice up-regulated genes that are involved in ion transport, such as Aqp2, Scnn1a, and Slc6a19, which indicated a response to maintain osmotic balance. In addition, we identified renoprotective biomarkers that are affected by MR, such as clusterin and cystatin C. Of importance, MR attenuated kidney injury in 5/6Nx mice by down-regulating inflammation and fibrosis mechanisms. Thus, our studies in mice show the important role of kidneys during MR in maintaining osmotic homeostasis. Moreover, our studies also show that the MR diet delays the progression of kidney disease.-Cooke, D., Ouattara, A., Ables, G. P. Dietary methionine restriction modulates renal response and attenuates kidney injury in mice.
Insights
Methionine restriction (MR) in mice leads to changes in kidney function and reduces kidney injury. This dietary intervention helps maintain osmotic balance and may delay kidney disease progression.
Area of Science:
- Gerontology
- Nephrology
- Nutritional Science
Background:
- Methionine restriction (MR) is known to extend lifespan across various species.
- While MR's health benefits are studied in organs like the liver and heart, its direct impact on kidneys remains under-explored.
- Understanding MR's renal effects is crucial for its application in healthspan extension.
Purpose of the Study:
- To investigate the direct effects of methionine restriction on kidney function and injury in mice.
- To identify renal biomarkers and molecular pathways modulated by MR.
- To assess MR's renoprotective potential, particularly in the context of kidney disease.
Main Methods:
- Utilized young and aged mice with unilateral nephrectomy and 5/6 nephrectomy (5/6Nx) models.
- Compared physiological and urinary parameters between MR mice and control-fed mice.
- Analyzed gene expression related to ion transport and identified renoprotective biomarkers.
- Evaluated the impact of MR on inflammation and fibrosis markers in kidney injury models.
Main Results:
- MR mice exhibited polydipsia and polyuria, with reduced urine albumin, creatinine, and sulfur amino acids.
- Upregulation of ion transport genes (Aqp2, Scnn1a, Slc6a19) in MR kidneys suggests osmotic balance maintenance.
- Identified clusterin and cystatin C as MR-affected renoprotective biomarkers.
- MR significantly attenuated kidney injury in 5/6Nx mice by reducing inflammation and fibrosis.
Conclusions:
- Kidneys play a significant role in maintaining osmotic homeostasis during methionine restriction.
- Methionine restriction demonstrates renoprotective effects and can attenuate kidney injury.
- MR diet shows potential in delaying the progression of kidney disease.
