PROGRESSION OF SARCOPENIA AND ASSOCIATED ELECTRON TRANSPORT SYSTEM ABNORMALITIES
E. A. Bua, S. H. McKiernan, M. Speleos and J. M. Aiken
University of Wisconsin
Department of Animal Health and Biomedical Sciences
1656 Linden Dr.
Madison, WI 53706
The involuntary loss of skeletal muscle mass and strength
with age, often referred to as sarcopenia, occurs between
25-70 years in humans. Sarcopenia is characterized by a
decrease in the muscle cross-sectional area with age due to
a reduction in muscle fiber number and/or fiber atrophy.
In addition to these age-related changes, an increase of
mitochondrial abnormalities (i.e. electron transport system
[ETS] abnormalities) with age has been demonstrated.
Our studies have suggested a link between mitochondrial
enzyme activity, mtDNA deletion mutations and fiber loss
with age.
The goal of this study was to define the progression of
sarcopenia and associated ETS abnormalities in muscles
from Fischer 344 x Brown Norway F1 rats with
age. Six groups of ad libitum fed rat (ages 18-, 21-, 24-,
27-, 30-, and 36-months) were used. The quadriceps muscles
were selected; rectus femoris [RF], vastus lateralis [VL],
vastus medialis [VM] and vastus intermedius [VI]. Total
body weight, individual muscle mass, fiber number and
muscle cross-sectional area (CSA) of each age group was
measured to define sarcopenia. Different patterns were
observed in terms of muscle mass changes: RF, VL and VM
muscle mass significantly decreased at 24- and 27-months
compared to 18-and 21-month, while VI muscle mass did not
change at any of the ages examined. While fiber number
at muscle mid-belly was similar within four muscles at 18-,
21-, 24-months, a significant decline was found in RF and
VL at 36-months. Tissue sections (10 microns thick) stained
for cytochrome c oxidase (COX) and succinate dehydrogenase
(SDH) activities were used to quantitate ETS abnormal
fibers (COX- and/or SDH++). COX-/SDH normal fibers were
present in middle-aged through very old aged rats in four
muscles examined, while COX-/SDH++ fibers were present only
in 36-month-old rats. Quantitation of the length of ETS
abnormal regions showed that COX-/SDH normal regions of
the fibers were smaller (30-240 microns) than the
COX-/SDH++ regions (100-680 microns). In addition,
only 5% of COX-/SDH normal fibers exhibited intra-fiber
atrophy, whereas 50% of COX-/SDH++ fibers examined were
atrophic.
This study suggests a progression from
COX normal/SDH normal to COX-/SDH normal to COX-/SDH++
phenotype and supports the causal role of mitochondrial
abnormalities in age-associated muscle fiber loss.
Key words:
sarcopenia, electron transport system abnormalities
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