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Mitochondrial dysfunction and age

Conley, Kevin Ea,b,c; Marcinek, David Ja; Villarin, Jasona

Current Opinion in Clinical Nutrition & Metabolic Care: November 2007 - Volume 10 - Issue 6 - p 688–692
doi: 10.1097/MCO.0b013e3282f0dbfb
Nutrition and physiological function: Edited by Wim H.M. Saris

Purpose of review Mitochondrial dysfunction is commonly thought to result from oxidative damage that leads to defects in the electron transport chain (ETC). In this review, we highlight new research indicating that there are early changes in mitochondrial function that precede ETC defects and are reversible thereby providing the possibility of slowing the tempo of mitochondrial aging and cell death.

Recent findings Increased mitochondrial uncoupling – reduced adenosine triphosphate (ATP) produced per O2 uptake – and cell ATP depletion are evident in human muscle nearly a decade before accumulation of irreversible DNA damage that causes ETC defects. New evidence points to reduction in activators of biogenesis (e.g. PGC-1α) and to degradation of mitochondria allowing accumulation of molecular and membrane damage in aged mitochondria. The early dysfunction appears to be reversible based on improved mitochondrial function in vivo and elevated gene expression levels after exercise training.

Summary New molecular and in vivo findings regarding the onset and reversibility of mitochondrial dysfunction with age indicate the potential: 1) for diagnostic tools to identify patients at risk for severe irreversible defects later in life; and 2) of an intervention to delay the tempo of aging and improve the quality of life of the elderly.

aDepartment of Radiology, University of Washington Medical Center, Seattle, Washington, USA

bDepartment of Physiology & Biophysics, University of Washington Medical Center, Seattle, Washington, USA

cDepartment of Bioengineering, University of Washington Medical Center, Seattle, Washington, USA

Correspondence to Kevin E. Conley, PhD, Department of Radiology, Box 357115, University of Washington Medical Center, 1959 NE Pacific Street, Seattle, WA 98195, USA Tel: +1 206 543 3763; fax: +1 206 543 3495; e-mail: kconley@u.washington.edu

© 2007 Lippincott Williams & Wilkins, Inc.