MITOCHONDRIAL DNA ABNORMALITIES AND FIBER ATROPHY IN RHESUS MONKEY SKELETAL MUSCLE.
Damian Lee, Zhengjin Cao, Marisol Lopez and Judd M. Aiken.
University of Wisconsin, Madison, WI 53706.
Sarcopenia is characterized by the loss of muscle mass with age.
It contributes to a loss of strength and an increase in physical
frailty in aged individuals. One proposed mechanism of
sarcopenia is the age-related accumulation of mitochondrial
abnormalities. Muscle mass loss presents as a decrease in
muscle cross-sectional area which has been attributed to
reduced fiber number and fiber atrophy. Our studies suggest
that mitochondrial DNA (mtDNA) deletion mutations are linked
to fiber atrophy and fiber loss. Intra-fiber atrophy was
examined in rhesus monkey quadriceps muscle (vastus lateralis)
by measuring cross-sectional area of ETS abnormal fibers
throughout the length of muscle fibers both within the ETS
abnormal region and in phenotypically normal regions. We found
ETS abnormal fibers to exhibit considerable intrafiber atrophy.
The length of the ETS abnormal region and degree of atrophy
increased with age of the rhesus monkey. Laser capture
microdissection was used to isolate sections of ETS abnormal
fibers for PCR based analysis of mtDNA deletions. Within
individual abnormal fibers deleted mtDNA could only be
detected in the fiber segment that concomitantly displayed the
ETS abnormal phenotype and not in adjacent phenotypically
normal regions. The identical deletion was detected at different
points within the same ETS abnormal fiber supporting a clonal
origin of these deletions. These results suggest a causal role of
age-associated mtDNA deletion mutations in sarcopenia.
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