Selenium supplementation inhibits IGF-1 signaling and confers methionine restriction-like healthspan benefits to mice

Abstract

Methionine restriction (MR) dramatically extends the healthspan of several organisms. Methionine-restricted rodents have less age-related pathology and increased longevity as compared with controls, and recent studies suggest that humans might benefit similarly. Mechanistically, it is likely that the decreased IGF-1 signaling that results from MR underlies the benefits of this regimen. Thus, we hypothesized that interventions that decrease IGF-1 signaling would also produce MR-like healthspan benefits. Selenium supplementation inhibits IGF-1 signaling in rats and has been studied for its putative healthspan benefits. Indeed, we show that feeding mice a diet supplemented with sodium selenite results in an MR-like phenotype, marked by protection against diet-induced obesity, as well as altered plasma levels of IGF-1, FGF-21, adiponectin, and leptin. Selenomethionine supplementation results in a similar, albeit less robust response, and also extends budding yeast lifespan. Our results indicate that selenium supplementation is sufficient to produce MR-like healthspan benefits for yeast and mammals.

Intermittent methionine restriction reduces IGF‐1 levels and produces similar healthspan benefits to continuous methionine restriction

“…show reduced insulin (but not glucose) levels in response to continuous MR (Plummer et al, 2021), a finding that is reproduced in the current study (Figure 4e). It is therefore notable that females undergoing the IMR2 regimen maintained relatively low blood glucose levels, the same as males undergoing either intermittent or continuous MR (Figure 2e).…”

“…While it is known that continuous MR both protects against liver steatosis and results in smaller sized livers (Ables et al, 2012 ; Malloy et al, 2013 ; Yang et al, 2019 ), we recently observed that another healthspan‐promoting dietary intervention ( i . e ., selenium supplementation) operates similarly in that it has a robust anti‐adiposity effect and produces smaller livers as compared with controls (Plummer et al, 2021 ). However, IMR only has the former activity, as liver mass was not significantly affected by this regimen (Figure 1g , Figure S3c ).…”

“…These experiments also differed from those performed for males with respect to the age of the animals. As we did previously for a study exploring the healthspan benefits of selenium supplementation (Plummer et al, 2021 ), we made use of adult females that were older (9 months old) than the males (5 months old) that featured in the above experiments. We favor this approach because we have observed that young female mice remain lean and metabolically healthy even when maintained on a high‐fat diet (not shown).…”

“…To the best of our knowledge, we show for the first time that IMR confers to male and female mice the beneficial metabolic effects previously reported for continuous MR. That is, as compared with control-fed mice, animals undergoing the more stringent of two IMR regimens (IMR2) benefit from reduced adipose tissue accumulation, protection against hepatosteatosis, improved glucose homeostasis, and altered circulating levels of IGF-1, FGF-21, leptin, and adiponectin. Despite a much shorter interventional period than continuous MR (only 3 days per week), not only is IMR capable of producing similar health benefits, but other aspects of this intervention are actually superior to classical MR. For example, while we have repeatedly observed that female mice have a somewhat limited response to continuous MR, with this intervention only partially improving their glucose homeostasis in the context of a high-fat diet (Plummer et al, 2021), IMR results in consistently low levels of both circulating glucose and insulin in both males and females. In addition, we find that the IMR regimen is fairly flexible, as similar healthspan benefits are produced whether the period of restriction is continuous (i.e., 3 contiguous days; IMR2) or interspersed with days of control feeding, as in the case of IMR2-A.…”

Multi-Functional Development and Utilization of Rapeseed: Comprehensive Analysis of the Nutritional Value of Rapeseed Sprouts

“…Rapeseed has diverse types of glucosinolates which vary greatly within rapeseed varieties, and thus rapeseed has great potential for genetic improvement [ 21 ]. Selenium, one of the essential elements for human body, is recognized as a “longevity element” [ 22 ]. Selenium-rich food is one of the main pathways for humans to obtain organic selenium.…”