X-Message-Number: 10656 Date: Thu, 29 Oct 1998 07:02:40 -0500 From: Thomas Donaldson <> Subject: CryoNet #10650 - #10654 To Brin Deela To Brian Delaney: I gave a partial answer to Jan Coetzee on the question you ask. I too have read these various experiments. I am not impressed by the depth of thinking that lay behind them. (I'll add, too, that you have not disposed of the "developmental program" explanation simply by the observation that CR works after puberty. We develop after puberty, too. Some authors claim that even aging comes under that heading). So here are some MORE suggestions, just to add to those I gave for Jan Coetzee. We note that CR restriction causes the CR animal to have a variety of metabolic differences from a normal animal. You suggest, for instance, that improved glucose regulation plays an important role in the effects of CR. Well, the obvious experiment is to take a population of NON-calorie restricted animals and try with drugs (chromium picolinate comes to mind, but aminoguanidine is worth trying too. And a good search is likely to find still others). Do these drugs produce similar effects to that of CR? If not, why not? Among other questions such a hypothesis suggests is simply that of finding the point at which the improved glucose regulation occurs --- after all, our cells deal with glucose using quite complicated metabolic machinery, especially our brain cells. It may or may not be of interest here that chromium picolinate does cause an increase in lifespan. I did not list it among those drugs for which an experiment shows an increase in maximal lifespan because the experiment showing an increase only provided a table of the number of animals surviving 1000 days, experimental versus controls. That chromium PICOLINATE worked while 2 other forms of chromium did not is also interesting. The aim of such an experiment is not just to decide that CR causes better regulation of glucose metabolism, but to work out in much more detail just how it does that. For that matter, if we did find a drug which reproduced the lifespan effects of CR in adult mice, the next step would be to see what it did to prepubertal mice, too. If it doesn't cause the same effects there, then the hypothesis is faulty. CR most certainly causes lots of metabolic changes. The only way to work out exactly which of these is primary and which is secondary is NOT to work only with CR mice, but instead to produce similar changes by other methods and see just what they do to the treated animals. That can be done by drugs or genetic manipulation of the mice, both of which are very well developed techniques. Repeated repetition of CR experiments, in which some new variable is measured, just isn't going to tell us very much at all. Best and long long life, Thomas Donaldson Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=10656