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Differences in Extent of Age‐related Atrophy Between Muscles is Associated with Mitochondrial ROS Production But Not with PTP Sensitivity
Author(s) -
Picard Martin,
Ritchie Darmyn,
Wright Kathryn J,
Thomas Melissa M,
Taivassalo Tanja,
Hepple Russell T
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1114.1
Subject(s) - mitochondrion , atrophy , reactive oxygen species , muscle atrophy , medicine , mitochondrial ros , mptp , chemistry , endocrinology , mitochondrial permeability transition pore , sarcopenia , superoxide dismutase , superoxide , apoptosis , oxidative stress , biology , biochemistry , enzyme , programmed cell death , dopaminergic , dopamine
Increases in mitochondrial reactive oxygen species (ROS) and susceptibility to mitochondrial‐driven apoptosis are implicated in the decline of muscle mass with aging. However, whether these changes in mitochondrial function explain the differential atrophy between muscles has not been determined. We hypothesized that age‐related increases in mitochondrial ROS production and increases in sensitivity of the mitochondrial permeability transition pore (mPTP) to Ca 2+ would be greater in muscles with greater degree of atrophy. Methods We prepared permeabilized myofibers from four muscles of young adult and senescent Fisher344/BN rats: 1) mixed gastrocnemius (mGas; fast twitch); 2) extensor digitorum longus (EDL; fast twitch); 3) soleus (Sol; slow twitch); and 4) adductor longus (AL; slow twitch). We measured mitochondrial H 2 O 2 release, Ca 2+ retention capacity (CRC) and activity of antioxidant enzymes. Results Muscle mass was significantly lower in SEN than in YA mGas (−38%), EDL (−21%), and SOL (−21%), but was higher in AL (+45%). When expressed per O 2 flux, H 2 O 2 release under State 3 respiration was 52% higher with aging only in mGas (mGas > Sol > EDL > AL). Adjusting data for H 2 O 2 scavenging potential of antioxidant enzymes increased theoretical H 2 O 2 release from fast‐twitch muscles and decreased that of slow‐twitch muscles (mGas > EDL > Sol > AL). Time to mPTP opening was lower only in EDL (−37%) and mGas (−29%), whereas the amount of Ca 2+ necessary to trigger opening of the PTP was lower (−19%) only in EDL. Conclusion Mitochondrial H 2 O 2 release was greater in the mGas muscle exhibiting the highest degree of atrophy. However, mPTP sensitivity to Ca 2+ was not associated with degree of atrophy. Differences in mitochondrial ROS but not mPTP sensitivity may explain differential atrophy between muscles with aging.