TY - JOUR
T1 - Update on the oxidative stress theory of aging
T2 - Does oxidative stress play a role in aging or healthy aging?
AU - Salmon, Adam B.
AU - Richardson, Arlan
AU - Pérez, Viviana I.
N1 - Funding Information:
This work was supported by NIH Training Grant T32 AG021890-05 ; NIH Grants R01AG015908 , R01AG023843 , P01AG19316 , P01AG020591 , and R37AG026557 ; an American Federation for Aging Research Senior Postdoctoral Grant; the Department of Veterans Affairs (Merit Grants and a Research Enhancement Award Program); and the San Antonio Nathan Shock Center of Excellence in the Basic Biology of Aging.
PY - 2010/3/1
Y1 - 2010/3/1
N2 - The oxidative stress theory of aging predicts that manipulations that alter oxidative stress/damage will alter aging. The gold standard for determining whether aging is altered is life span, i.e., does altering oxidative stress/damage change life span? Mice with genetic manipulations in their antioxidant defense system designed to directly address this prediction have, with few exceptions, shown no change in life span. However, when these transgenic/knockout mice are tested using models that develop various types of age-related pathology, they show alterations in progression and/or severity of pathology as predicted by the oxidative stress theory: increased oxidative stress accelerates pathology and reduced oxidative stress retards pathology. These contradictory observations might mean that (a) oxidative stress plays a very limited, if any, role in aging but a major role in health span and/or (b) the role that oxidative stress plays in aging depends on environment. In environments with minimal stress, as expected under optimal husbandry, oxidative damage plays little role in aging. However, under chronic stress, including pathological phenotypes that diminish optimal health, oxidative stress/damage plays a major role in aging. Under these conditions, enhanced antioxidant defenses exert an "antiaging" action, leading to changes in life span, age-related pathology, and physiological function as predicted by the oxidative stress theory of aging.
AB - The oxidative stress theory of aging predicts that manipulations that alter oxidative stress/damage will alter aging. The gold standard for determining whether aging is altered is life span, i.e., does altering oxidative stress/damage change life span? Mice with genetic manipulations in their antioxidant defense system designed to directly address this prediction have, with few exceptions, shown no change in life span. However, when these transgenic/knockout mice are tested using models that develop various types of age-related pathology, they show alterations in progression and/or severity of pathology as predicted by the oxidative stress theory: increased oxidative stress accelerates pathology and reduced oxidative stress retards pathology. These contradictory observations might mean that (a) oxidative stress plays a very limited, if any, role in aging but a major role in health span and/or (b) the role that oxidative stress plays in aging depends on environment. In environments with minimal stress, as expected under optimal husbandry, oxidative damage plays little role in aging. However, under chronic stress, including pathological phenotypes that diminish optimal health, oxidative stress/damage plays a major role in aging. Under these conditions, enhanced antioxidant defenses exert an "antiaging" action, leading to changes in life span, age-related pathology, and physiological function as predicted by the oxidative stress theory of aging.
KW - Aging
KW - Disease
KW - Free radicals
KW - Health span
KW - Life span
KW - Oxidative stress
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U2 - 10.1016/j.freeradbiomed.2009.12.015
DO - 10.1016/j.freeradbiomed.2009.12.015
M3 - Review article
C2 - 20036736
AN - SCOPUS:75149165994
SN - 0891-5849
VL - 48
SP - 642
EP - 655
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 5
ER -