Transient systemic mtDNA damage leads to muscle wasting by reducing the satellite cell pool

Xiao Wang, Alicia M. Pickrell, Susana G Rossi, Milena Pinto, Lloye M. Dillon, Aline Hida, Richard L Rotundo, Carlos T Moraes

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 languageEnglish
Pages (from-to)3976-3986
Number of pages11
JournalHuman Molecular Genetics
Volume22
Issue number19
DOIs
StatePublished - Oct 1 2013

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Muscles
Sarcopenia
Premature Aging
Phenotype
Frail Elderly
Muscular Atrophy
Neuromuscular Junction
Locomotion
Acetylcholinesterase
Muscle Cells

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 journalArticle

Wang, Xiao ; Pickrell, Alicia M. ; Rossi, Susana G ; Pinto, Milena ; Dillon, Lloye M. ; Hida, Aline ; Rotundo, Richard L ; Moraes, Carlos T. / Transient systemic mtDNA damage leads to muscle wasting by reducing the satellite cell pool. In: Human Molecular Genetics. 2013 ; Vol. 22, No. 19. pp. 3976-3986.
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