TY - JOUR
T1 - Ischemia/reperfusion unveils impaired capacity of older adults to restrain oxidative insult
AU - Davies, Sean S.
AU - Traustadóttir, Tinna
AU - Stock, Anthoney A.
AU - Ye, Fei
AU - Shyr, Yu
AU - Harman, S. Mitchell
AU - Roberts, L. Jackson
N1 - Funding Information:
We acknowledge the Vanderbilt CRC nursing staff, for their assistance in conducting these studies, and Chris Bodine, Tamjeed Ahmed, William Zackert, and Tom Nguyen for their technical assistance in the biochemical analysis. We also thank James May and Fiona Harrison for their assistance in performing the ascorbate assays. This research was supported in part by MERIT Grant GM42056 to L.J.R. from NIH/NIGMS and Vanderbilt CTSA Grant 1UL1RR024975 from NCRR/NIHM01. Experiments completed at KLRI were supported by a grant from the Aurora Foundation to T.T. and S.M.H.
PY - 2009/10/1
Y1 - 2009/10/1
N2 - Age independently predicts poor outcome in a variety of medical settings, including sepsis, trauma, severe burns, and surgery. Because these conditions are associated with oxidative stress, we hypothesized that the capacity to constrain oxidative insult diminishes with age, leading to more extensive oxidative damage during trauma. To test this hypothesis, we used suprasystolic inflation of an arm blood pressure cuff to safely induce localized forearm ischemia/reperfusion (I/R) and quantified plasma F2-isoprostane (IsoP) levels in serial blood samples. Before I/R, IsoP levels were similar in young (20-33 years) and older adults (62-81 years). After I/R challenge, the magnitude and duration of increased IsoP levels was significantly greater in older adults. Because aging is associated with declining levels of sex hormones that contribute to the regulation of antioxidant enzyme expression, we then examined the response to I/R in older women receiving hormone replacement therapy and found that these women did not manifest the amplified IsoP response found in untreated older women. These findings demonstrate that aging impairs the ability to restrain oxidative damage after an acute insult, which may contribute to the increased vulnerability of older adults to traumatic conditions and establishes a useful method to identify effective interventions to ameliorate this deficiency.
AB - Age independently predicts poor outcome in a variety of medical settings, including sepsis, trauma, severe burns, and surgery. Because these conditions are associated with oxidative stress, we hypothesized that the capacity to constrain oxidative insult diminishes with age, leading to more extensive oxidative damage during trauma. To test this hypothesis, we used suprasystolic inflation of an arm blood pressure cuff to safely induce localized forearm ischemia/reperfusion (I/R) and quantified plasma F2-isoprostane (IsoP) levels in serial blood samples. Before I/R, IsoP levels were similar in young (20-33 years) and older adults (62-81 years). After I/R challenge, the magnitude and duration of increased IsoP levels was significantly greater in older adults. Because aging is associated with declining levels of sex hormones that contribute to the regulation of antioxidant enzyme expression, we then examined the response to I/R in older women receiving hormone replacement therapy and found that these women did not manifest the amplified IsoP response found in untreated older women. These findings demonstrate that aging impairs the ability to restrain oxidative damage after an acute insult, which may contribute to the increased vulnerability of older adults to traumatic conditions and establishes a useful method to identify effective interventions to ameliorate this deficiency.
KW - Aging
KW - Free radicals
KW - Hormone replacement therapy
KW - Ischemia/reperfusion
KW - Isoprostanes
KW - Lipid peroxidation
KW - Oxidative injury
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U2 - 10.1016/j.freeradbiomed.2009.07.005
DO - 10.1016/j.freeradbiomed.2009.07.005
M3 - Article
C2 - 19596063
AN - SCOPUS:69249229459
SN - 0891-5849
VL - 47
SP - 1014
EP - 1018
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 7
ER -