2-Deoxy-D-Glucose Feeding in Rats Mimics Physiologic Effects of Calorie Restriction

Summary: There's almost nothing interesting to say about 2-deoxy-D-glucose yet.

Interestingness: 1

Paper by Mark A Lane, Donald K Ingram and George S Roth in the Journal of Anti-Aging Medicine, Volume 1, Issue 4, Winter 1998.

(((The previous paper was about the effects of calorie restriction (CR). This one is by the same group of people, about a potential CR mimic (ie a substance that has similar effects to practicing CR). I assume there will be many more of these type of papers through the rest of the journal history)))

Since CR is unlikely to be taken up by a large proportion of the population, it'd be good to find substances that trigger the same effects. While the mechanism by which CR extends lifespan is unknown, there are many hypotheses, including reduced oxidative stress, elevated glucocorticoids, reduction in body temperature, and altered glucose metabolism. This study looks at this last one by introducing a substance into rats diet, 2-deoxy-D-glucose (2DG), that is a competitive inhibitor of glycolysis. 2DG is phosphorylated by hexokinase (((energy-consuming step))), but the process stops there (((no energy released))).

120 rats were split into four groups of 25 and one group of 20, the smaller group acting as a control, three other groups being fed 0.2, 0.4 and 0.6 percent 2DG, and the final group matched to consume only as much food as the group taking the smallest amount out of the rest (((to control for direct CR effects I think))). The study lasted 24 weeks and started when the rats were 6 weeks old.

Since four rats died in the first 5 weeks in the high dose group, the diet was modified to be one week of 0.6% 2DG intermixed with a week free of 2DG (((hack))). There was one death in each of the two other dose groups but they were not attributed to 2DG.

In all but two of the 2DG rats, autopsies of rats killed at the half way point and at the end of the study showed vacuoles in their heart (((holes of fluid?))). Food intake was slightly (5%) lower in the 2DG rats throughout the study. Weight was also a lot lower throughout in the higher 2DG dose rats, and in the pair matched (((about 10% from the graph))), and a little lower in the 0.4% group (((5% or so))), with very low variance. Temperature was also lower in the two higher dose groups (((by about 0.25 degrees from the graph, even though the text says 0.5 degrees))), but variance was higher. Finally, insulin levels were lower in the 0.4% dose group at both autopsy points (((by about 25% with respect to controls))), but no statistical effect on glucose (((but still a bit lower))).

(((0.6% kills, and 0.2% has no effect, and they all leave holes in the heart. The supposedly beneficial effects in the 0.4% group are not impressive (lower weight, slightly lower temperature, lower insulin) and were matched by the pair-matched group in all but temperature. Lifespan data would be nice, but until then there's nothing to see here)))


Abstract follows:

Calorie restriction (CR) extends the life span, slows the rate of aging, and delays the onset of many age-related diseases in short-lived laboratory species, primarily rodents. Although it is unknown if CR extends the life span in long-lived mammals, findings emerging from CR studies in rhesus monkeys agree with the extensive rodent literature that suggests this intervention can have beneficial effects in primates. Even if CR is shown to extend the life span in long-lived species, it is unlikely that the 30% to 40% reduction in intake used typically in this paradigm would become a widespread practice in humans. An alternative strategy may be to design interventions that "mimic" biologic effects of CR but do not significantly reduce food intake. The present study was designed to test the hypothesis that administration of a glucose analogue, 2-deoxy-D-glucose (2-DG) would mimic certain effects of CR. Specifically, we administered three doses (0.2%, 0.4%, and 0.6% w/w) of 2-DG in the diet to male Fischer-344 rats. Rats fed 0.4% 2-DG weighed slightly less than controls and exhibited significant reductions in body temperature and fasting serum insulin levels. Our findings suggest that it might be possible to design interventions to mimic certain metabolic effects, and perhaps other beneficial effects of CR such as life span extension and retardation of physiologic aging.