Principal Investigator and Helen P. Rumbel Professor for Healthy Aging Research, Linus Pauling Institute
Professor, Department of Biochemistry and Biophysics
335 Linus Pauling Science Center
541-737-5083 / 541-737-5077 (Fax)
Our research seeks to identify the mode of action of two “age-essential” micronutrients, lipoic acid (LA) and acetyl-Lcarnitine (ALCAR).
Our work has shown that ALCAR and LA improve two of the most important cellular lesions of aging: the inability to respond to oxidative and toxicological challenges and the loss of mitochondrial function. We are currently exploring why these stress response mechanisms decline with age and are particularly focusing on cellular signaling pathways that LA may induce to activate Nrf2-mediated gene expression.
Mitochondria may be the “Achilles’ heel” of cellular aging because their dysfunction adversely affects conversion of dietary fuels into useful energy, dysregulates cellular calcium levels, increases oxidative stress, and limits tissue renewal. Another goal of my laboratory is to determine whether these age-essential micronutrients can improve human health by maintaining mitochondrial function.
Thomas NO, Shay KP, Kelley AR, Butler JA, Hagen TM. (2016) Glutathione maintenance mitigates age-related susceptibility to redox cycling agents. Redox Biol 10:45-52.
Smith EJ, Shay KP, Thomas NO, Butler JA, Finlay LF, Hagen TM. (2015) Age-related loss of hepatic Nrf2 protein homeostasis: Potential role for heightened expression of miR-146a. Free Radic Biol Med 89:1184-1191.
Keith D, Finlay L, Butler J, Gómez L, Smith E, Moreau R, Hagen T. (2014) Lipoic acid entrains the hepatic circadian clock and lipid metabolic proteins that have been desynchronized with advanced age. Biochem Biophys Res Commun 450:324-329.
Michels AJ, Hagen TM, Frei B. (2013) Human genetic variation influences vitamin C homeostasis by altering vitamin C transport and antioxidant enzyme function. Annu Rev Nutr 33:45-70.
Keith DJ, Butler JA, Bemer B, Dixon B, Johnson S, Garrard M, Sudakin DL, Christensen JM, Pereira C, Hagen TM. (2012) Age and gender dependent bioavailability of R- and R,S-α-lipoic acid: a pilot study. Pharmacol Res 66:199-206.