X-Message-Number: 25555
Date: Sat, 15 Jan 2005 12:24:10 -0800 (PST)
From: Doug Skrecky <>
Subject: trace episodic hydrogen peroxide as a life extender?

    [Episodic 20 mM H2O2 increased human skin cell longevity in vitro by 60%.
(ref #1) This intriguing result has not (yet) been followed up on with an
in vivo rodent longevity experiment. There was one study on house flies
which found that a steady state concentration of 10 mM H2O2 in drinking
water increased average lifespan by 9%. (ref #2) However 5 mM H2O2
reduced lifespan by 16%, and 100 mM H2O2 reduced it by 27%. Although 10
mM increased fly's glutathione by 98%, 5 mM actually decreased this by 8%.
    Perhaps it is just as well that a potential antiaging medication
commonly found in the house has been ignored. High doses of hydrogen
peroxide accelerate cellular senescence, and anyone taking very low
"hormetic" doses  of it to prevent aging would be playing Russian
roulette, with the philosophy that "what does not kill me makes me
stronger." Try terminalia chebula instead. This is a lot safer.]

(reference #1)
J Cell Biochem. 2004 Oct 15;93(3):588-97.
Slow-down of age-dependent telomere shortening is executed in human skin
keratinocytes by hormesis-like-effects of trace hydrogen peroxide or by
anti-oxidative effects of pro-vitamin C in common concurrently with
reduction of intracellular oxidative stress.
     The cellular life-span of cultivated human skin epidermis
keratinocytes NHEK-F was shown to be extended up to 150% of population
doubling levels (PDLs) by repetitive addition with two
autooxidation-resistant derivatives of ascorbic acid (Asc),
Asc-2-O-phosphate (Asc2P), and Asc-2-O-alpha-glucoside (Asc2G),
respectively, but to be not extended with Asc itself. In contrast,
hydrogen peroxide (H(2)O(2)) as dilute as 20 microM which was
non-cytotoxic to the keratinocytes, or at 60 microM being marginally
cytotoxic achieved the cellular longevity, unexpectedly, up to 160
and 120% of PDLs, respectively,  being regarded as a hormesis-like
stimulatory effect. The lifespan -extended cells that were administered
with Asc2P, Asc2G, or 20 microM H(2)O(2) were prevented from
senescence-induced symptoms such as PDL-dependent enlargement of a cell
size of 14.7 microm finally up to 17.4 microm upon Hayflick's limit-called
loss of proliferation ability as estimated with a channelizer, and
retained young cell morphological aspects such as thick and compact
shape and intense attachment to the culture substratum even upon advanced
PDLs, whereas other non-extended cells looked like thin or fibrous shape
and large size upon lower PDLs. The PDL-dependent shortening of telomeric
DNA of 11.5 kb finally down to 9.12-8.10 kb upon Hayflick's limit was
observed in common for each additive-given cells, but was decelerated in
the following order: 20 microM H(2)O(2) > Asc2P = Asc2G > 60 microM
H(2)O(2) > Asc = no additive, being in accord with the order of cell
longevity. Intracellular reactive oxygen species (ROS) was diminished by
Asc2P, Asc2G or 20 microM H(2)O(2), but not significantly by Asc or 60
microM H(2)O(2) as estimated by fluorometry using the redox indicator dye
CDCFH. There was no appreciable difference among NHEK keratinocytes that
were administered with or without diverse additives in terms of
telomerase activity per cell, which was 1.40 x 10(4)-4.48 x 10(4) times
lower for the keratinocytes than for HeLa cells which were examined as
the typical tumor cells. Thus longevity of the keratinocytes was suggested
to be achieved by slowdown of age-dependent shortening of telomeric DNA
rather than by telomerase; telomeres may suffer from less DNA lesions due
to the continuous and thorough repression of intracellular ROS, which was
realized either by pro-vitamin C such as Asc2P or Asc2G that exerted an
antioxidant ability more persistent than Asc itself or by 20 microM
H(2)O(2) which diminished intracellular ROS assumedly through a
hormesis-like effect.

(reference #2)
Exp Gerontol. 1988;23(3):211-6.
Effect of hydrogen peroxide administration on life span, superoxide
dismutase, catalase, and glutathione in the adult housefly, Musca domestica.
    The general objective of this study was to further elucidate the
relationship between oxidative stress and the aging process. H2O2 is
known to be a progenator of reactive oxygen species, such as hydroxyl
free radical, by various mechanisms involving, among others, a superoxide
anion radical-driven Fenton cycle, or splitting of the 0-0 bond by
hemoproteins. Effects of H2O2 administration on life span, activities of
superoxide dismutase, catalase, concentrations of endogenous H2O2, and
glutathione in the housefly are described. Adult male flies were given
various concentrations of H2O2, ranging from 0 to 100 mM H2O2, in their
drinking water. Life span was shortened by H2O2 intake except in 10 mM
H2O2 administrated flies, which exhibited the longest life span. Flies
administered 10 mM H2O2 also contained the highest concentration of
reduced glutathione (GSH). Superoxide dismutase and catalase activities
were not affected by H2O2 intake. Compensatory elevation in GSH may be
responsible for the increase in life span observed in 10 mM H2O2
administered flies.

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