Selenium: The Powerful Mineral that Protects Against Obesity and May Extend Lifespan

If you dig deep into your high school science memory bank, you may recall that every single protein that’s synthesized starts with an amino acid called methionine. But this protein building block is not only made by our cells, it is also found in meat, fish, and dairy products. 

Perhaps counterintuitively, given its importance in building proteins, restricting diets from methionine dramatically extends the healthspan of several organisms. Methionine-restricted rodents have less age-related pathology and increased longevity, and recent studies suggest that humans might benefit similarly. This is thought to happen through a decrease in cell signaling related to a compound called Insulin-Like Growth Factor 1 (IGF-1). So, is it possible that interventions that decrease IGF-1 signaling would also produce healthspan benefits like those seen with methionine restriction?

In an article published in eLife, Plummer and colleagues show that feeding mice a diet supplemented with selenium — a known inhibitor of IGF-1 signaling — results in a protection against diet-induced obesity. In yeast, selenium supplementation extended their lifespan.

“One of the goals of the aging field is the identification of simple interventions that promote human healthspan,” said Plummer and colleagues in the article. “While multiple dietary interventions have been identified, including methionine restriction, that promote mammalian healthspan, a pharmacologic intervention would arguably be preferable. Our results indicate that selenium supplementation is sufficient to produce methionine restriction-like healthspan benefits for yeast and mammals.”

Methionine restriction can postpone meeting your maker

It has been well established that methionine restriction can improve mammalian health- and lifespan. Among the varied benefits of methionine restriction to rodents, there is an improvement in metabolic health, marked by reduced white fat tissue accumulation, amelioration of liver steatosis (aka, ‘fatty liver disease’), and improved glycemic control. In fact, these metabolic benefits are so robust that methionine restriction provides complete protection against diet-induced obesity, which results from feeding animals a high-fat diet meant to approximate the human Western diet.

Research suggests that methionine-restricted humans are likely to receive similar healthspan benefits as rodents. As the vegan diet is naturally low in proteins and free amino acids, a methionine-restricted diet is technically feasible for humans. However, such a diet might not be practical for all individuals, and as a result, widespread adherence is likely to be problematic. Besides, consumption of a diet low in amino acids other than methionine and cysteine, both of which must be restricted for efficient methionine restriction, might result in undesirable side effects.

This begs the question: Is there an intervention that produced the benefits associated with methionine restriction (MR), but in the context of a normal, methionine-replete diet? An important clue for the identification and development of such an intervention that is effective in a methionine-replete context is the observation that there is a decrease in the circulating levels of the energy-regulating hormone IGF-1. What’s more is that decreased IGF-1 signaling mediates the health benefits of these regimens and, further, may actually be sufficient to extend healthspan.

It turns out that a powerful mineral called selenium dramatically reduces IGF-1 levels, which raises the possibility that, by doing so, it might also confer MR-like healthspan benefits. So, this is what Plummer and colleagues set out to test: whether selenium supplementation might confer methionine restriction-like benefits to mice by reducing circulating IGF-1 levels.

Shedding aging with selenium

The research team from Weill Cornell Medicine fed mice an otherwise normal high-fat diet containing sodium selenite and assessed whether, like methionine restriction, this intervention protects against diet-induced obesity. They measured circulating IGF-1 levels and assessed multiple other bodily parameters known to be altered by methionine restriction, as well as the ability of other selenium sources to support any benefits associated with sodium selenite supplementation.

Plummer and colleagues show that selenium supplementation alters IGF-1 levels and confers a variety of healthspan benefits typically associated with methionine restriction in mice. These mice had low levels of fat tissue accumulation, protection against fatty liver, and improved glycemic control. They also saw reductions in the levels of the hormone leptin, which controls food intake and energy expenditure.

These results were not only seen in complex, multi-cellular organisms like mice but were also replicated in yeast. Supplementing yeast with selenium produced major anti-aging benefits. They found that selenium supplementation resulted in a 62% extension of maximum lifespan in aged yeast compared to those that weren’t supplemented (21 days vs 13 days). Plummer and colleagues then wrapped up their research article by trying to pinpoint some of the ways the selenium was working its anti-aging magic in yeast.

How much selenium is enough to stock up on extra years?

So if short-term supplementation with selenium results in total protection against diet-induced obesity, what will happen in the long term? Plummer and colleagues expect that, in the long term, this intervention will also produce a methionine restriction-like extension of overall survival, as well as an amelioration of age-related pathologies. Should this prove to be the case, one can only hope that the pro-longevity pathways engaged by such interventions are sufficiently conserved that humans will receive similar benefits to mammalian counterparts.

“One of the major goals of aging research is to identify simple interventions that promote human healthspan,” notes senior author Jay Johnson, Senior Scientist at OFAS. “Here we present evidence that short-term administration of either organic or inorganic sources of selenium provides multiple health benefits to mice, the most notable of which being the prevention of diet-induced obesity. In the long term, we expect that supplementation with these compounds will also prevent age-related disease and extend the overall survival of mice. It is our hope that many of the benefits observed for mice will also hold true for humans.”

References: 

Plummer JD, Postnikoff SD, Tyler JK, Johnson JE. Selenium supplementation inhibits IGF-1 signaling and confers methionine restriction-like healthspan benefits to mice. Elife. 2021;10:e62483. Published 2021 Mar 30. doi:10.7554/eLife.62483