X-Message-Number: 25661
Date: Thu, 3 Feb 2005 20:41:58 -0800 (PST)
From: Doug Skrecky <>
Subject: EC-SOD & aging

[Experiments in a test tube have to be taken with a grain of salt.]

J Biol Chem. 2003 Feb 28;278(9):6824-30. Epub 2002 Dec 09
Extracellular superoxide dismutase is a major antioxidant in human
fibroblasts and slows telomere shortening.
  There is good evidence that telomere shortening acts as a biological
clock in human fibroblasts, limiting the number of population doublings a
culture can achieve. Oxidative stress also limits the growth potential of
human cells, and recent data show that the effect of mild oxidative
stress is mediated by a stress-related increased rate of telomere
shortening. Thus, fibroblast strains have donor-specific antioxidant
defense, telomere shortening rate, and growth potential. We used
low-density gene expression array analysis of fibroblast strains with
different antioxidant potentials and telomere shortening rates to identify
gene products responsible for these differences. Extracellular
superoxide dismutase was identified as the strongest candidate, a
correlation that was confirmed by Northern blotting. Over-expression of
this gene in human fibroblasts with low antioxidant capacity increased
total cellular superoxide dismutase activity, decreased the intracellular
peroxide content, slowed the telomere shortening rate, and elongated the
life span of these cells under normoxia and hyperoxia. These results
identify extracellular superoxide dismutase as an important antioxidant
gene product in human fibroblasts, confirm the causal role of oxidative
stress for telomere shortening, and strongly suggest that the
senescence-like arrest under mild oxidative stress is telomere-driven.

[Why do humans grey with age? - hmmm]

Photochem Photobiol. 2004 Dec;80(3):579-82
Protective Effect of Superoxide Dismutase Against Hair Graying in a Mouse
Model paragraph sign.
  Oxygen free radicals play a role in the aging process, and the
protective effect of various antioxidants has been intensively studied,
in particular for cutaneous aging. Besides hereditary factors, free
radical-mediated damage to melanocytes of the hair follicle has been
considered as a mechanism for aging of the hair. It was the aim of this
study to evaluate the role of photosensitization reactions for hair
graying and to demonstrate potential protective effects of superoxide
dismutase (SOD). Mice with black hair were depilated with the fingertips
on a surface of 6 x 2.5 cm on both sides of the dorsum. The right side
received five applications of a SOD-containing gel before exposure to
psoralen (concentration 0.5 mg/mL) plus UV-A (365 nm, 4 J/cm(2)). The
left side was pretreated in the same way with a gel free of SOD. When the
hair started growing again, the SOD-protected side was covered with black
hair, whereas the hair on the vehicle-treated side was gray or white in
27 of the 30 animals studied. The 0.01% SOD concentration was as
protective as the 0.1% concentration. Heat-inactivated SOD, applied in
another five animals, was not protective. Using fluorescent labeling of
the SOD with fluorescein isothiocyanate, epifluorescence microscopy and
digital imaging processing, we show that SOD applied to the skin surface
penetrates through the follicular appendages, as well as through the
unbroken stratum corneum. Our findings suggest that superoxide radicals,
generated by interaction of UV-A light with the sensitizer, initiated the
formation of secondary products with well-known DNA-damaging effects,
such as lipid peroxidation products and tumor necrosis factor alpha. SOD
prevented the damage to melanocyte DNA by dismutating superoxide.
Photosensitization may be another mechanism for hair graying, which can be
influenced by antioxidants. Given the large number of exogenous and
endogenous sensitizers, this mechanism deserves further study for human
hair graying.

[Superoxide scavenging may account for the effect of terminalia chebula,
uncaria sinensis, or epimedium flavonoids on telomeres.]

Phytother Res. 2004 Sep;18(9):737-41.
Cytoprotective effect on oxidative stress and inhibitory effect on
cellular aging of Terminalia chebula fruit.
  The ethanol extract from the fruit of Terminalia chebula (Combretaceae)
exhibited significant inhibitory activity on oxidative stress and the
age-dependent shortening of the telomeric DNA length. In the peroxidation
model using t-BuOOH, the T. chebula extract showed a notable
cytoprotective effect on the HEK-N/F cells with 60.5 +/- 3.8% at a
concentration of 50 microg/ml. In addition, the T. chebula extract
exhibited a significant cytoprotective effect against UVB-induced
oxidative damage. The life-span of the HEK-N/F cells was elongated by 40%
as a result of the continuous administration of 3 microg/ml of the T.
chebula extract compared to that of the control. These observations were
attributed to the inhibitory effect of the T. chebula extract on the
age-dependent shortening of the telomere, length as shown by the Southern
blots of the terminal restriction fragments (TRFs) of DNA extracted from
subculture passages.

J Ethnopharmacol. 2004 Dec;95(2-3):127-32.
Cytoprotective effect on oxidative stress and inhibitory effect on
cellular aging of Uncaria sinensis Havil.
  The ethanol extract from the hooks and stems of Uncaria sinensis Havil
(Rubiaceae) exhibited significant inhibitory activity on oxidative stress
and the age-dependent shortening of the telomeric DNA length. In the
peroxidation model using t-BuOOH, the Uncaria sinensis extract showed a
notable cytoprotective effect on the HEK-N/F cells with 65.0 +/- 3.0% of
cell viability when compared with control cells at a concentration of 50
microg/ml. In addition, the Uncaria sinensis extract exhibited a
significant cytoprotective effect against UVB-induced oxidative damage.
The life-span of the HEK-N/F cells was elongated by 201% as a result of
the continuous administration of 3 microg/ml of the Uncaria sinensis
extract compared to that of the control. These observations were
attributed to the inhibitory effect of the Uncaria sinensis extract on
the age-dependent shortening of the telomere length as shown by the
Southern blots of the terminal restriction fragments (TRFs) of DNA
extracted from subculture passages.


Zhongguo Zhong Xi Yi Jie He Za Zhi. 2004 Dec;24(12):1094-7.
[Experimental study on effect of epimedium flavonoids in protecting
telomere length of senescence cells HU]
  OBJECTIVE: To investigate the mechanism of senescence delay of human
diploid fibroblast (2BS) and protecting telomere length by epimedium
flavonoids (EF). METHODS: The drug sera of EF were used to treat the 2BS.
The population doublings of 2BS cells were observed, the mRNA expression
of p16 gene were determined by fluorescence real-time quantitative RT-PCR,
the telomerase activation of 2BS cells were determined by TRAP-Hyb, the
total retinoblastoma (Rb) and phosphorated Rb protein content were
detected by ELISA, the telomere length of 2BS cells were determined by
telomere restriction fragment (TRF) Southern blot assay. RESULTS: EF
could significantly extend the population doublings of 2BS cells, the
expression of p16 mRNA was decreased and the content of phosphorated Rb
protein were increased by EF. The telomere lengthening of 2BS cells were
improved by EF, but the telomerase was not activated. CONCLUSION: In
senescence human fibroblasts 2BS cells, p16 gene mRNA expression
increased, content of phosphorated Rb protein decreased and the telomere
length of 2BS shortened, EF might delay the aging of cells through
inhibiting the p16 gene expression, promoting the production of
phosphorated Rb protein and to protect the length of telomere, but not
activating the telomerase.

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