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.

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