Methionine restriction delays aging-related urogenital diseases in male Fischer 344 rats

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Dietary methionine restriction (MR) has been found to enhance longevity across many species. We hypothesized that MR might enhance longevity in part by delaying or inhibiting age-related disease processes. To this end, male Fischer 344 rats were fed control (CF, 0.86% methionine) or MR (0.17% methionine) diets throughout their life until sacrifice at approximately 30 months of age, and histopathology was performed to identify the incidence and progression of two important aging-related pathologies, namely, chronic progressive nephropathy (CPN) and testicular tumorigenesis. Although kidney pathology was observed in 87% CF rats and CPN in 62% of CF animals, no evidence of kidney disease was observed in MR rats. Consistent with the absence of renal pathology, urinary albumin levels were lower in the MR group compared to controls throughout the study, with over a six-fold difference between the groups at 30 months of age. Biomarkers associated with renal disease, namely, clusterin, cystatin C, and β-2 microglobulin, were reduced following 18 months of MR. A reduction in testicular tumor incidence from 88% in CF to 22% in MR rats was also observed. These results suggest that MR may lead to metabolic and cellular changes providing protection against age-related diseases.

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Authors would like to thank Dr. Abraham Rivenson, at American Health Foundation, Valhalla, NY for performing the histopathological examination on rat tissues in a blinded manner.


We dedicate this paper to the memory of Norman Orentreich, MD. Dr. Orentreich was the first to describe methionine restriction as a means to extend lifespan and promote healthy aging. His commitment to the study of aging continues to inspire us as we move forward in our research.

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Correspondence to Raghu Sinha or John P. Richie Jr.

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Komninou, D., Malloy, V.L., Zimmerman, J.A. et al. Methionine restriction delays aging-related urogenital diseases in male Fischer 344 rats. GeroScience (2019).

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  • Aging
  • Nephropathy
  • Metabolic changes
  • Methionine restriction
  • Testicular cancer