Low Methionine Ingestion by Rats Extends Life Span

Orentreich Foundation for the Advancement of Science, Inc., Biomedical Research Station, Cold Spring-on-Hudson, NY 10516.
Journal of Nutrition (Impact Factor: 3.88). 03/1993; 123(2):269-74.
Source: PubMed


Dietary energy restriction has been a widely used means of experimentally extending mammalian life span. We report here that lifelong reduction in the concentration of a single dietary component, the essential amino acid L-methionine, from 0.86 to 0.17% of the diet results in a 30% longer life span of male Fischer 344 rats. Methionine restriction completely abolished growth, although food intake was actually greater on a body weight basis. Studies of energy consumption in early life indicated that the energy intake of 0.17% methionine-fed animals was near normal for animals of their size, although consumption per animal was below that of the much larger 0.86% methionine-fed rats. Increasing the energy intake of rats fed 0.17% methionine failed to increase their rate of growth, whereas restricting 0.85% methionine-fed rats to the food intake of 0.17% methionine-fed animals did not materially reduce growth, indicating that food restriction was not a factor in life span extension in these experiments. The biochemically well-defined pathways of methionine metabolism and utilization offer the potential for uncovering the precise mechanism(s) underlying this specific dietary restriction-related extension of life span.

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    • "This was also pointed out by Buffenstein[30]. Methionine restriction is one of the most powerful dietary regimens resulting in longer lifespan[31]. Interestingly , it has been reported that methionine restriction leads to a decrease in CBS protein levels[2]. Hence, low CBS activity in the naked mole-rat liver may be an adaptation to a low methionine diet. "
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    ABSTRACT: Hydrogen sulfide (H2S) is a gaseous signalling molecule involved in many physiological and pathological processes. There is increasing evidence that H2S is implicated in aging and lifespan control in the diet-induced longevity models. However, blood sulfide concentration of naturally long-lived species is not known. Here we measured blood sulfide in the long-lived naked mole-rat and five other mammalian species considerably differing in lifespan and found a negative correlation between blood sulfide and maximum longevity residual. In addition, we show that the naked mole-rat cystathionine β-synthase (CBS), an enzyme whose activity in the liver significantly contributes to systemic sulfide levels, has lower activity in the liver and is activated to a higher degree by S-adenosylmethionine compared to other species. These results add complexity to the understanding of the role of H2S in aging and call for detailed research on naked mole-rat transsulfuration.
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    • "Numerous studies have documented a contribution of methionine metabolism and its restriction to beneficial metabolic health including the extension of mammalian life span, the acquisition of resistance to diet-induced obesity, and the therapeutic efficacy of ketogenic diets (Kraus et al., 2014; Malloy et al., 2006; Orentreich et al., 1993; Pissios et al., 2013). In each of these cases, the biological mechanisms contributing to these outcomes are largely unknown. "
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    • "However, an important distinction between these dietary approaches is that dietary MR does not require restriction of food intake. Quite the contrary, animals on the MR diet develop hyperphagia but paradoxically gain significantly less weight than animals on the control diet [1]. Careful pair-feeding studies showed that dietary MR increased the energy costs of maintaining body weight and decreased the accumulation of fat [4], prima facie evidence that dietary MR impacts energy balance by increasing total energy expenditure (EE). "
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