The paradoxical role of thioredoxin on oxidative stress and aging.
In spite of intensive study, there is still controversy about the free radical or oxidative stress theory of aging, particularly in mammals. Our laboratory has conducted the first detailed studies on the role of thioredoxin (Trx) in the cytosol (Trx1) and in mitochondria (Trx2) on oxidative stress and aging using unique mouse models either overexpressing or down-regulating Trx1 or Trx2. The results generated from our lab and others indicate that: (1) oxidative stress and subsequent changes in signaling pathways could have different pathophysiological impacts at different stages of life; (2) changes in redox-sensitive signaling controlled by levels of oxidative stress and redox state could play more important roles in pathophysiology than accumulation of oxidative damage; (3) changes in oxidative stress and redox state in different cellular compartments (cytosol, mitochondria, or nucleus) could play different roles in pathophysiology during aging, and their combined effects show more impact on aging than changes in either oxidative stress or redox state alone; and (4) the roles of oxidative stress and redox state could have different pathophysiological consequences in different organs/tissues/cells or pathophysiological conditions. To critically test the role of oxidative stress on aging and investigate changes in redox-sensitive signaling pathways, further study is required.
Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, United States.
Geneva M
GM
Cunningham
Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, United States.
Madeline G
MG
Roman
Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, United States.
Lisa C
LC
Flores
Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, United States; Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, United States.
Gene B
GB
Hubbard
Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, United States; Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, United States; Geriatric Research and Education Clinical Center, Audie L. Murphy VA Hospital South Texas Veterans Health Care System, San Antonio, TX 78229, United States.
Adam B
AB
Salmon
Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, United States.
Yiqiang
Y
Zhang
Department of Epidemiology & Biostatistics, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, United States.
Jonathan
J
Gelfond
Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, United States; Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, United States; Research Service, Audie L. Murphy VA Hospital South Texas Veterans Health Care System, San Antonio, TX 78229, United States; Geriatric Research and Education Clinical Center, Audie L. Murphy VA Hospital South Texas Veterans Health Care System, San Antonio, TX 78229, United States. Electronic address: Ikeno@uthscsa.edu.
Yuji
Y
Ikeno
D000375:Aging; D000818:Animals; D015536:Down-Regulation; D006801:Humans; D008136:Longevity; D018384:Oxidative Stress; D013879:Thioredoxins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation
D013879:Thioredoxins
Aging; Cancer; Knockout mouse; Oxidative stress; Thioredoxin; Transgenic mouse