Fight Aging!

Heavy isotopes are variants of atoms with one or more extra neutrons. Only some configurations are stable, such as the deuterium in heavy water, hydrogen with an extra neutron, or carbon-14, containing two more neutrons than the standard carbon atom. The chemical properties of a heavy isotope are slightly different, usually too slight to matter: heavy water is the exception to the rule, as it is toxic in large amounts, while heavy carbon isotopes appear to have little to no effect on living organisms. In recent years it has been shown that raising short-lived species, those with quite plastic life spans, on a low dosage of heavy water appears to modestly slow aging. This may be because it grants greater resistance to oxidative damage for some important parts of cell's molecular machinery, but may also simply be a matter of hormesis, in that a low level of damage or toxicity triggers greater levels of cell maintenance and repair, leading to a net benefit. From a practical point of view, this, like all ways to modestly slow aging, is probably only of interest as a tool for those researchers attempting to map the biochemistry of aging. It isn't a path to rejuvenation.

In a recent effort to look for the intrinsic factors that cause aging, we have discovered a potential candidate. By examining the intracellular small-molecule metabolites in yeast cells undergoing aging, we found that as yeast cells age, the overall heavy isotopic content, such as that of carbon-13, nitrogen-15, and hydrogen-2 (deuterium) declines in the amino acids, an essential group of metabolites that serve as building blocks in protein biosynthesis and precursors in all living organisms. Moreover, supplementing heavy isotopes through nutritional uptake extends the lifespan of yeast by more than 80% in aging assays, likely via eliciting a dietary-restriction-like effect. If this observed trend represents a wide-spread phenomenon in the isotopic composition of the metabolome, proteome, and genome in other organisms as well, new perspectives on understanding aging and retarding the end of life may open up.

Before our observation of heavy isotope decline during organismal aging, deuterium-bearing heavy water has been shown to promote longevity or improve certain health aspects in several organisms, including fruit flies, rodents, and humans. In fruit flies, transient exposure to heavy water at juvenile stages extends lifespan, and the exposure does not affect the health and reproduction. However, a dosage of 50% heavy water shortens the lifespan, and the relative lifespan shortening by heavy water was ameliorated by temperature elevation from 10 to 30°C, suggesting a protective effect of heavy water on fruit fly survival in hot conditions where accelerated metabolic rate normally reduces longevity. Improved thermoresistance was indeed observed at the protein, cell, and organism levels in fruit flies upon heavy water treatment. Similarly, a driving factor in temperature-compensated effects by heavy water was observed to alter the phase relation in circadian oscillation. The heavy water effect is increasingly more pronounced with rising temperature. However, the mechanism is still unknown. The similarity in the biological responses between heavy water and low temperature also correlate well with the general observation that fruit flies and worms have longer lifespan, and retarded brain degeneration when maintained at low temperature.

Several functional studies have shown that deuterated polyunsaturated fatty acids, even supplied in a minor fraction (20-50%), can protect yeast and mammalian cells from reactive oxygen species (ROS) damage to mitochondria. In whole animals, 25% heavy water was able to normalize high blood pressure induced by high salt diet in rats, possibly through suppressing hypertension-related elevation in calcium uptake. These effects would surely extend lifespan. In yeast, we also showed that heavy water extends chronological lifespan in a dosage-dependent manner. This pro-longevity effect could be essentially abrogated by mild dietary restriction or mitochondrion removal. Heavy water also suppresses the endogenous ROS generation, which could ameliorate the background chemical damages from ROS and lead to long-term improvement in fitness and survival rate. All these protective effects indicate that heavy water functions as a metabolism modifier to promote longevity, a feature that could be amenable to implementation in the context of other well-known anti-aging interventions.

Link: http://onlinelibrary.wiley.com/doi/10.1002/bies.201600040/full