Bioenergetics and permeability transition pore opening in heart subsarcolemmal and interfibrillar mitochondria: Effects of aging and lifelong calorie restriction

Tim Hofer, Stephane Servais, Arnold Young Seo, Emanuele Marzetti, Asimina Hiona, Shashank Jagdish Upadhyay, Stephanie Eva Wohlgemuth, Christiaan Leeuwenburgh

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

Loss of cardiac mitochondrial function with age may cause increased cardiomyocyte death through mitochondria-mediated release of apoptogenic factors. We investigated ventricular subsarcolemmal (SSM) and interfibrillar (IFM) mitochondrial bioenergetics and susceptibility towards Ca2+-induced permeability transition pore (mPTP) opening with aging and lifelong calorie restriction (CR). Cardiac mitochondria were isolated from 8-, 18-, 29- and 37-month-old male Fischer 344 × Brown Norway rats fed either ad libitum (AL) or 40% calorie restricted diets. With age, H2O2 generation did not increase and oxygen consumption did not significantly decrease in either SSM or IFM. Strikingly, IFM displayed an increased susceptibility towards mPTP opening during senescence. In contrast, Ca2+ retention capacity of SSM was not affected by age, but SSM tolerated much less Ca2+ than IFM. Only modest age-dependent increases in cytosolic caspase activities and cytochrome c levels were observed and were not affected by CR. Levels of putative mPTP-modulating components: cyclophilin-D, the adenine nucleotide translocase (ANT), and the voltage-dependent ion channel (VDAC) were not affected by aging or CR. In summary, the age-related reduction of Ca2+ retention capacity in IFM may explain the increased susceptibility to stress-induced cell death in the aged myocardium. © 2009 Elsevier Ireland Ltd. All rights reserved.
Lingua originaleEnglish
pagine (da-a)297-307
Numero di pagine11
RivistaMechanisms of Ageing and Development
Volume130
DOI
Stato di pubblicazionePubblicato - 2009

Keywords

  • Heart disease
  • Hypertrophy
  • Ischemia-reperfusion
  • Senescence

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