Abstract
With age, musclemassandintegrity are progressively lost leaving the elderly frail,weakandunable to independently care for themselves. Defined as sarcopenia, this age-related muscle atrophy appears to be multifactorial but its definite cause is still unknown. Mitochondrial dysfunction has been implicated in this process. Using a novel transgenic mousemodel ofmitochondrialDNA(mtDNA) double-strand breaks (DSBs) that presents a premature aging-like phenotype, we studied the role of mtDNA damage in muscle wasting. We caused DSBs in mtDNA of adult mice using a ubiquitously expressed mitochondrial-targeted endonuclease, mito-PstI. We found that a short, transient systemic mtDNA damage led to muscle wasting and a decline in locomotor activity later in life.Wefound a significant decline in muscle satellite cells, which decreases the muscle's capacity to regenerate and repair during aging. This phenotype was associated with impairment in acetylcholinesterase (AChE) activity and assembly at the neuromuscular junction (NMJ), also associated with muscle aging. Our data suggests that systemic mitochondrial dysfunction plays important roles in age-related muscle wasting by preferentially affecting the myosatellite cell pool.
| Original language | English |
|---|---|
| Pages (from-to) | 3976-3986 |
| Number of pages | 11 |
| Journal | Human Molecular Genetics |
| Volume | 22 |
| Issue number | 19 |
| DOIs | |
| State | Published - Oct 1 2013 |
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ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
- Molecular Biology
Cite this
Transient systemic mtDNA damage leads to muscle wasting by reducing the satellite cell pool. / Wang, Xiao; Pickrell, Alicia M.; Rossi, Susana G; Pinto, Milena; Dillon, Lloye M.; Hida, Aline; Rotundo, Richard L; Moraes, Carlos T.
In: Human Molecular Genetics, Vol. 22, No. 19, 01.10.2013, p. 3976-3986.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Transient systemic mtDNA damage leads to muscle wasting by reducing the satellite cell pool
AU - Wang, Xiao
AU - Pickrell, Alicia M.
AU - Rossi, Susana G
AU - Pinto, Milena
AU - Dillon, Lloye M.
AU - Hida, Aline
AU - Rotundo, Richard L
AU - Moraes, Carlos T
PY - 2013/10/1
Y1 - 2013/10/1
N2 - With age, musclemassandintegrity are progressively lost leaving the elderly frail,weakandunable to independently care for themselves. Defined as sarcopenia, this age-related muscle atrophy appears to be multifactorial but its definite cause is still unknown. Mitochondrial dysfunction has been implicated in this process. Using a novel transgenic mousemodel ofmitochondrialDNA(mtDNA) double-strand breaks (DSBs) that presents a premature aging-like phenotype, we studied the role of mtDNA damage in muscle wasting. We caused DSBs in mtDNA of adult mice using a ubiquitously expressed mitochondrial-targeted endonuclease, mito-PstI. We found that a short, transient systemic mtDNA damage led to muscle wasting and a decline in locomotor activity later in life.Wefound a significant decline in muscle satellite cells, which decreases the muscle's capacity to regenerate and repair during aging. This phenotype was associated with impairment in acetylcholinesterase (AChE) activity and assembly at the neuromuscular junction (NMJ), also associated with muscle aging. Our data suggests that systemic mitochondrial dysfunction plays important roles in age-related muscle wasting by preferentially affecting the myosatellite cell pool.
AB - With age, musclemassandintegrity are progressively lost leaving the elderly frail,weakandunable to independently care for themselves. Defined as sarcopenia, this age-related muscle atrophy appears to be multifactorial but its definite cause is still unknown. Mitochondrial dysfunction has been implicated in this process. Using a novel transgenic mousemodel ofmitochondrialDNA(mtDNA) double-strand breaks (DSBs) that presents a premature aging-like phenotype, we studied the role of mtDNA damage in muscle wasting. We caused DSBs in mtDNA of adult mice using a ubiquitously expressed mitochondrial-targeted endonuclease, mito-PstI. We found that a short, transient systemic mtDNA damage led to muscle wasting and a decline in locomotor activity later in life.Wefound a significant decline in muscle satellite cells, which decreases the muscle's capacity to regenerate and repair during aging. This phenotype was associated with impairment in acetylcholinesterase (AChE) activity and assembly at the neuromuscular junction (NMJ), also associated with muscle aging. Our data suggests that systemic mitochondrial dysfunction plays important roles in age-related muscle wasting by preferentially affecting the myosatellite cell pool.
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U2 - 10.1093/hmg/ddt251
DO - 10.1093/hmg/ddt251
M3 - Article
VL - 22
SP - 3976
EP - 3986
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 19
ER -