Are the core statements of the free

Are the core statements of the free radical theory
of aging proven false?
The core statements of the free radical theory of aging are not
proven false, contrary to the speculation or conclusions made by a
number of authors [21–23], because these speculations are based
on inconclusive and often confusing research. Let us examine
some of the arguments:
(a) The failure of SOD mimics to extend the life span of some
species is not a valid argument, because the mimics discussed
[22,24] probably do not act as such in vivo and the wild-type
organisms have enough SOD to overwhelm the relatively
miniscule additive effect of the mimics. As already discussed,
superoxide by itself causes mostly metabolic slowdown.
(b) Many trials have concluded that antioxidant-rich diets do not
extend either life span or the overall health of control individuals!
It is indisputable that glutathione, ascorbate, and vitamin E act as
antioxidants and in different organisms they are either synthe-
sized or supplied by the normal diet. However, in the reactions
with radicals or ROS they are usually not irreparably modified but
subjected to one- or two-electron oxidations, and the products of
such oxidations are then reductively repaired. Hence, the rate-
limiting processes are those of this reductive reactivation and in
fact part of the adaptation to oxidative stress is due to upregula-
tion of those reductive reactivations. Supplements of ascorbate
and vitamin E will be oxidized rapidly, especially under oxidative
stress, because in that situation the processes of reductive
reactivation have problems with maintaining the normal level
of their reduced forms. Not surprisingly, vitamin supplementation
makes sense only in the cases of unbalanced diet and situations
in which vitamins are rapidly metabolized. Other natural com-
pounds of plant origin thought to act as ROS scavengers may
instead be agents that trigger beneficial adaptations toward
oxidative stress.
(c) Rather than being toxic, modestly elevated levels of oxidants
are proposed to be beneficial, extending life span, for exam-
ple, by acting as prosurvival signals [21–24]! As discussed in
point (b) above, this effect has been seen in very primitive
tiny animals living unnatural protected lifestyles on a suffi-
cient but potentially unbalanced and/or suboptimal diet, and
at the expense of their overall health. In fact, C. elegans prefers
Bacillus mycoides and Bacillus soli to E. coli as a source of food,
and the sole feeding of these bacteria to C. elegans results in
extended life span, probably by activating autophagic pro-
cesses [28]. Hence, triggering autophagic processes and/or
other beneficial adaptations lacking in animals living pro-
tected lifestyles may indeed be involved in the reported [23]
life-extending effects of mild to moderate oxidative stress.
An interesting and conclusive paper by Pickering et al. [29] has
just appeared in Free Radical Biology & Medicine. Thus in the
S.I. Liochev / Free Radical Biology and Medicine 60 (2013) 1–4
3
biologically relevant situation of chronic and especially repeated
stress, caused by low levels of administered hydrogen peroxide,
adaptation to stress was seen. These treatments led to a signifi-
cant decrease of the life span of fruit flies. That hydrogen peroxide
triggered adaptation toward oxidative stress but certainly did not
act as a life-extending (prosurvival) agent is in accordance with
the expectations of the traditional view.

Kết quả (Việt) 1:

Có những điều khoản cốt lõi của lý thuyết gốc tự dolão hóa đã được chứng minh sai?Những điều khoản cốt lõi của lý thuyết gốc tự do lão hóa khôngchứng minh sai, trái ngược với suy đoán hoặc kết luận được thực hiện bởi mộtsố của tác giả [21-23], bởi vì những suy đoán được dựanghiên cứu bất phân thắng bại và thường khó hiểu. Hãy để chúng tôi kiểm tradự tất cả hay một số các đối số:(a) sự thất bại của SOD bắt chước để kéo dài cuộc sống span của một sốloài không phải là một đối số hợp lệ, vì bắt chước các thảo luận[22,24] có lẽ không hành động như là như vậy tại vivo và loại hoangsinh vật có đủ SOD để áp đảo các tương đốitác dụng phụ gia rất nhỏ của các bắt chước. Như đã thảo luận,superoxide của chính nó gây ra chủ yếu là trao đổi chất chậm.(b) nhiều thử nghiệm đã kết luận rằng chế độ ăn giàu chất chống oxy hoá khôngkéo dài tuổi thọ hoặc sức khỏe tổng thể của cá nhân kiểm soát!Nó là không thể chối cãi rằng glutathione, ascorbate và vitamin E hoạt động nhưchất chống oxy hóa và trong sinh vật khác nhau, họ là một trong hai synthe -có kích thước hoặc được cung cấp bởi chế độ ăn uống bình thường. Tuy nhiên, trong các phản ứngvới gốc do hoặc ROS họ được thường không irreparably thay đổi nhưngmột hoặc hai điện tử oxidations, và các sản phẩm củaCác oxidations sau đó reductively sửa chữa. Do đó, tỷ lệ -hạn chế quá trình là những số này kích hoạt công và trongthực tế là một phần của thích ứng với stress oxy hóa là do upregula-tion của những reactivations công. Bổ sung ascorbateand vitamin E will be oxidized rapidly, especially under oxidativestress, because in that situation the processes of reductivereactivation have problems with maintaining the normal levelof their reduced forms. Not surprisingly, vitamin supplementationmakes sense only in the cases of unbalanced diet and situationsin which vitamins are rapidly metabolized. Other natural com-pounds of plant origin thought to act as ROS scavengers mayinstead be agents that trigger beneficial adaptations towardoxidative stress.(c) Rather than being toxic, modestly elevated levels of oxidantsare proposed to be beneficial, extending life span, for exam-ple, by acting as prosurvival signals [21–24]! As discussed inpoint (b) above, this effect has been seen in very primitivetiny animals living unnatural protected lifestyles on a suffi-cient but potentially unbalanced and/or suboptimal diet, andat the expense of their overall health. In fact, C. elegans prefersBacillus mycoides and Bacillus soli to E. coli as a source of food,and the sole feeding of these bacteria to C. elegans results inextended life span, probably by activating autophagic pro-cesses [28]. Hence, triggering autophagic processes and/orother beneficial adaptations lacking in animals living pro-tected lifestyles may indeed be involved in the reported [23]life-extending effects of mild to moderate oxidative stress.An interesting and conclusive paper by Pickering et al. [29] hasjust appeared in Free Radical Biology & Medicine. Thus in the
S.I. Liochev / Free Radical Biology and Medicine 60 (2013) 1–4
3
biologically relevant situation of chronic and especially repeated
stress, caused by low levels of administered hydrogen peroxide,
adaptation to stress was seen. These treatments led to a signifi-
cant decrease of the life span of fruit flies. That hydrogen peroxide
triggered adaptation toward oxidative stress but certainly did not
act as a life-extending (prosurvival) agent is in accordance with
the expectations of the traditional view.