The Basic Biology of Aging at the University of Washington
Kevin Conley, Ph.D.

Biosketch Information
Email: kconley@u.washington.edu

This research focuses on the decline in mitochondrial function with age under resting (state 4) and exercising or maximal (state 3) conditions. Muscle is one of the largest organs of the body and its decline with age has profound impacts on the function of elderly individuals. Our goal is to understand the cellular basis for this loss of muscle function. This research focuses on novel approaches and methods involving magnetic resonance and optics in mouse hindlimb to characterize mitochondrial functional changes with age in mouse muscle in vivo. These methods allow us the unprecedented ability to quantitatively measure oxidative phosphorylation using simultaneous determinations of respiration and phosphorylation rate of muscle in vivo.

Our first aim is to test a hypothesis: the leakiness of mitochondria increases with age as measured by a decrease in ATP synthesized per O2 consumed (lower ATP/O2). Our second aim tests another hypothesis: the decline in mitochondrial oxidative capacity with age parallels the loss of respiratory chain enzyme activity (e.g., cytochrome oxidase). The tools developed here will provide techniques for studying in vivo muscle and organ function in transgenic and mouse models of disease. The experiments themselves point the way for targeted in vitro work to discern the basis of the in vivo functional changes found in aging muscle.

Dr. Conley is Professor of Departments of Radiology and Physiology & Biophysics and Adjunct Professor of Bioengineering. He has served on: Scientific Review Board, American Heart Association, 1996-present; National Scientific Advisory Council, American Federation for Aging Research, 1997-present; NIH study sections (ad hoc reviewer), Molecular, Cellular and Developmental Neurosciences; Respiratory and Applied Physiology; Metabolism, 2000-01.

Selected Relevant Publications
Conley KE, Jubrias SA, Esselman PE. Oxidative capacity and aging in human muscle. J Physiol 526:203-210, 2000.

Conley KE, Esselman PE, Jubrias SA, Cress ME, Inglin B, Mogadam C, Schoene RS. Aging, muscle properties and maximum O2 uptake rate in humans. J Physiol 526:211-217, 2000.

Kemper WF, Lindstedt SL, Hartzler LK, Hicks JW, Conley KE. Shaking-up glycolysis: sustained, high lactate flux during aerobic rattling. Proc Natl Acad Sci USA 98:723-728, 2001.

Jubrias, SA, Esselman PC, Price LB, Cress ME, Conley KE. Large energetic adaptations of elderly muscle to resistance and endurance training. J Appl Physiol 90:1663-1670, 2001.

Conley, KE, Kemper WF, Crowther GJ. Limits to sustainable muscle performance: interaction of glycolysis and respiration. J Exp Biol 204:3185-3194, 2001.

Lindstedt SL, Conley KE. Human aerobic performance: too much ado about limits to VO2. J Exp Biol 204:3195-3199, 2001.

Crowther, GJ, Kemper WF, Carey MF, Conley KE. The control of glycolysis in contracting skeletal muscle. I. Turning it on. Am J Physiol Endocinol Metab 282:E67-E73, 2002.

Crowther, GJ, Kemper WF, Carey MF, Conley KE. The control of glycolysis in contracting skeletal muscle. II. Turning it off. Am J Physiol Endocinol Metab 282:E74-E79, 2002. Moon BR, Hopp JJ, Conley KE. Getting more for less: Mechanical trade-offs allow force and work to increase without increasing cost in rattlesnake tailshaker muscle. J Exp Biol 205:667-675, 2002.