X-Message-Number: 26353 Date: Sat, 18 Jun 2005 13:13:36 -0700 (PDT) From: Doug Skrecky <> Subject: free radicals, mitochondria, & chromium picolinate Message #26339 From: Thomas Donaldson <> >To Doug Skrecky: > You begin your message with a statement which directly contradicts the > abstract of the paper you include in your message. What do you mean > here? > [For clarification regarding catalase mutants please see below.] > As a matter of fact, apparently production of antioxidant chemicals > has been compared across a few species. Humans apparently make > more per cell than do mice or rats (I'll get you the reference > if you want it). > [It is a myth that humans have more antioxidant chemicals. Human tissue is less well protected against free radicals than that of rat tissue. However you may have read that human tissue produces fewer free radicals in the first place, has greater repair, and is more resistant to free radical attack in general. Humans are a lot tougher, but this is not due to greater antioxidants.] Cardiovascular Research 1993;27:2052-2057 "Antioxidant defences in rat, pig, guinea pig, and human hearts: comparison with xanthine oxidoreductase activity" Abstract conclusions: Rat hearts are far better protected against H2O2 than the other three species. ... Human myocardium seems less protected against superoxide radicals. [A very considerable doubt about the free radical theory of aging has been raised by the following null result.] Physiol Genomics 16: 29-37 2003 "Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging" Quote from Abstract: The increased oxidative damage to DNA in the Sod2+/- mice is associated with a 100% increase in tumor incidence (the number of mice with tumors) in old Sod2+/- mice compared with the old WT mice. However, the life spans (mean and maximum survival) of the Sod+/- and WT mice were identical. ... Thus life-long reduction of MnSOD activity leads to increased levels of oxidative damage to DNA and increased cancer incidence but does not appear to affect aging. [On the flip side we have the following:] Science Epub May 5, 2005 "Extension of Murine Life Span by Overexpression of Catalase Targeted to Mitochondria" Note: Although the abstract did not mention this, the full report concluded that there was no statistically significant difference in lifespan in either peroxisome (PCAT) or nucleus (NCAT) transgenetic mice. Quote: "The lifespan extension in mitochondria (MCAT) transgenetic mice was less than that achieved by caloric restriction or dwarfism or that observed in other genetic models of delayed and decelerated aging." [So the question remains: Do free radicals have anything at all to do with aging? I do not have an answer, and I suspect neither does anybody else. However one could piece together a partial answer based on the existing data. If free radicals do have a major impact on aging, this would be in the mitochondrial compartment. In addition, there appears to be a theshold above which mitochondrial derived free radicals cease to directly affect aging processes. Whether reducing free radical generation in mitochondria below a theshold value can greatly slow aging processes in mammals, is a hypothesis that remains to be demonstrated. Apparently this does work in the fungus podospora anserina. However all the above may mean next to nothing. Here's why: The provocative results with chromium picolinate still remain to be accounted for. I thank Thomas for mailing a photocopy of this report from a defunct medical journal. (Advances in Scientific Research 1(1): 19-23) Chromium picolinate fed Long-Evans rats had a record median longevity of 1316 days, compared to 1041-1059 days for the two control groups fed chromium chloride, and chromium nicotinate respectively. Maximum longevity of 1441 days was likewise outstanding considering only ten animals were used. Control maximums were 1132-1154 days. My own radical interpretation is that the artificial diets that rodents have always been subjected to during longevity tests greatly shortened their lifespans by induction of hyperglycemia. Said diets notably lacked the insulin sensitising ingrediants to be found in "healthy" natural ingrediant diets. If the lifespan of rodents is always shortened by such maltreatment then this would throw into doubt every rodent longevity test that has ever been done. (Guess which ingrediant is the most common in rodent chow: apples, oranges, or white table sugar). One could start by red-flagging the effect of life long severe (44%) calorie restriction on Long-Evans rats. (J Appl Physiol 70(4): 1529-1535) Average survival for these animals was 1088 days and maximum survival was 1341 days. Both of these figures are significantly surpassed (1316, 1441 days) by those of fully fed animals given chromium picolinate. Long-Evans rats can live even longer than this. When female rats were fed sodium selenate average survival was just 1014 days, but maximum survival was 1830 days (over 5 years!). (J Nutr 101: 1531-1540) The significance of all this? A replication of the experiment with chromium picolinate with a larger number of animals is arguably the highest priority task for experimental gerontologists. If the provocative results already obtained are confirmed they would effectively render null and void virtually all other rodent longevity research. This would then have to be regarded as being contaminated by malnutrition related hyperglycemia. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=26353