Heavy Water Extends Yeast Lifespan

A few years ago a revolutionary new method to prevent oxidative damage to proteins was introduced by the Russian biochemist Mikhail Shchepinov. While we generally think that isotopes have identical chemical behavior, after all that’s what our high school teacher used to tell us, this is not fully correct. Isotopes do have subtle differences in chemical behavior such as bond strength. The bond formed by a heavier isotope is stronger. For example, the carbon-deuterium bond is about 5 to 10-fold stronger than the carbon-hydrogen bond. Deuterium is the heavier isotope of normal hydrogen. A previous study already demonstrated that free radical production is decreased in isolated rat mitochondria exposed to heavy water. 

Can heavy water increase lifespan?

In the new study published in npj Aging and Mechanisms of Disease researchers from Stanford University School of Medicine demonstrate that administration of heavy water to baker's yeast increases lifespan. This experiment was inspired by their observation that the amount of amino acids carrying heavy isotopes decreased with age. Such an age-related decline may also happen in other metabolites but due to technical limitations these authors could not study that. 

The researchers also tested the effect of heavy water administration on lifespan in three different longevity gene mutants (gpr1Δ, sir2Δ, and tor1Δ). Lifespan extension in these mutants was similar to wild type, showing that heavy water extends lifespan independent of these genes. On the other hand, heavy water only moderately extended the lifespan of yeast cells lacking mitochondrial DNA. Thus the mechanism by which heavy water extends lifespan is dependent on mitochondrial metabolism.

Reducing free radical production

The researchers also measured the production of free radicals in yeast cells grown in the presence of heavy water. The presence of heavy water resulted in a significant reduction in intracellular and in mitochondrial free radical production in all three yeast strains, confirming the hypothesis of Mikhail Shchepinov. It is however also possible that the reduction in free radical production is caused, not by ‘hardening’ cellular macromolecules to damage, but by reducing the metabolism of the cells. The researchers cite an old study that found no effect of heavy water on oxygen consumption by yeast cells. Furthermore, the yeast cells grown in heavy water had growth curves similar to control cells, excluding the possibility that heavy water causes an extreme reduction in energy metabolism. 

The authors also proposed a novel hypothesis on how heavy water could lead to life extension. As we saw earlier, heavy isotopes have a lower chemical reactivity. This means that hydrolysis reactions will be lower in heavy water.  

Image attribution: Sven Bulterijs, based on data from Li and Snyder (2016)

Image attribution: Sven Bulterijs, based on data from Li and Snyder (2016)

In 2013 Michael R. Rose and colleagues published a study in which they show that brief administration of low amounts of deuterium oxide (heavy water) to fruit flies extended their lifespan. It will be interesting to discover if mice fed deuterium oxide also live longer… 

The use of isotopically-reinforced molecules as therapeutics against age-related diseases such as Alzheimer’s disease is already being pursued by the pharmaceutical startup Retrotrope

Curiously, while some work on increasing the amount of deuterium as a strategy to improve health others have investigated the exact opposite. In a paper published in 1999 it was found that feeding deuterium-depleted water increased survival after radiation in ... Given that the harmful effects of radiation are caused by free radical damage to cellular components such as proteins and DNA it would make sense that deuterium-depleted water should worsen survival not improve it. So, much more research into the health effects of deuterium is needed.  

   

Bild W, Stefanescu I, Haulica I, Lupuşoru C, Titescu G, Iliescu R, Nastasa V (1999). Research concerning the radioprotective  and immunostimulating effects of deuterium-depleted water. Rom J Physiol 36(3-4): 205-218.

Pomytkin IA, Kolesova OE (2006). Relationship between natural concentration of heavy water isotopologs and rate of H2O2 generation by mitochondria. Bull Exp Biol Med 142(5): 570-572.   

Hammel SC, East K, Shaka AJ, Rose MR, Shahrestani P (2013). Brief early-life non-specific incorporation of deuterium extends mean life span in Drosophila melanogaster without affecting fecundity. Rejuvenation Res 16: 98-104. 

Li X, Snyder MP (2016). Yeast longevity promoted by reversing aging-associated decline in heavy isotope content. npj Aging and Mechanisms of Disease 2: 16004.