Guest essay by Eric Worrall
What do we miss out on because the world wastes so much money and attention on climate? Imagine if some of that squandered money was spent on other fields such as medical research, such as the following accidental discovery, which if developed offers the possibility of longer life and superhuman athletic prowess.
Born to run; the story of the PEPCK-Cmus mouse
Richard W. Hanson and Parvin Hakimi
In order to study the role of the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (EC 184.108.40.206) (PEPCK-C) in skeletal muscle, PEPCK-Cmus mice were created by introducing the cDNA for the enzyme, linked to the human α-skeletal actin gene promoter, into their germ line. Two founder lines generated by this procedure were bred together, creating a line of mice that have 9.0 units/g skeletal muscle, as compared to 0.080 units/g in muscle from control animals. The mice were more active than controls in their cages and could run for up to 5 km, at a speed of 20 m/min without stopping (control mice run for 0.2 km at the same speed). Male PEPCK-Cmus mice are extremely aggressive, as well as hyperactive. During strenuous exercise, they use fatty acids as a fuel more efficiently than do controls and produce far less lactate than do control animals, perhaps due to the greatly increased number of mitochondria in their skeletal muscle. PEPCK-Cmus mice also store up to five-times more triglyceride in their skeletal muscle, but have only marginal amounts of triglyceride in their adipose tissue depots, despite eating 60% more than controls. The concentration of leptin and insulin the blood of 8 to 12 month of PEPCK-Cmus mice is far lower than noted in the blood of control animals of the same age. These mice live longer than controls and the females remain reproductively active for as long as 35 months. The possible reasons for the profound alteration in activity and longevity caused the introduction of a simple metabolic enzyme into the skeletal muscle of the mice will be discussed.
One undesirable side effect was the mice were more aggressive. This was a major concern for the scientists who conducted the study. But the study mice were seriously souped up. The researchers wanted to understand the effect of the PEPCK-C modification, so they didn’t mess about, they increased levels of PEPCK-C to over 100x natural levels.
There are obvious questions – for example, would 10x natural levels, or even 2x natural levels, produce health benefits without the aggression?
This startling discovery occurred in 2008. Since then, as far as I know it has remained a laboratory curiosity. I’m not aware of any effort to find a way to turn this startling discovery into a therapeutic treatment, for people suffering the effects of old age.
The researchers point out some difficulties with turning this metabolic tweak into a therapeutic treatment, for example they don’t think that current gene therapies would be effective in modifying adult cells, currently the modification has to be applied in-vitro to embryos. But these are surely problems to be solved, we shouldn’t simply accept them as insurmountable obstacles.
Because if this modification could be realised as a treatment which could be applied to humans, it could have a remarkable effect on human health. Eat as much as you want, live like an athletic 20 year old until the very end of your life, a lifespan many decades longer than we currently enjoy.
All this from one small change. How many other small beneficial changes to metabolism are potentially available, just waiting for some researcher to stumble across them?
The answer to the question, what is the opportunity cost of climate waste? The answer is it costs us our life – decades of healthy, active life we could have had, if the money squandered on climate was directed towards something useful.
The following video shows just how dramatic the impact of the PEPCK-C modified metabolism is – two mice on a treadmill, one with the modification, one without.