ArticlePloS one2013
Mitochondrial biogenesis drives a vicious cycle of metabolic insufficiency and mitochondrial DNA deletion mutation accumulation in aged rat skeletal muscle fibers.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Aging in the Skeletal Muscle Revealed by Molecular Immunohistochemical Imaging.International journal of molecular sciences · 2025Review
- Chimeric mitochondrial RNA transcripts predict mitochondrial genome deletion mutations in mitochondrial genetic diseases and aging.Genome research · 2025Article
- Selection promotes age-dependent degeneration of the mitochondrial genome.bioRxiv : the preprint server for biology · 2024Article
- Age- and time-dependent mitochondrial genotoxic and myopathic effects of beta-guanidinopropionic acid, a creatine analog, on rodent skeletal muscles.GeroScience · 2023Article
- Remdesivir does not affect mitochondrial DNA copy number or deletion mutation frequency in aged male rats: A short report.PloS one · 2022Article
- Exercise rescues mitochondrial coupling in aged skeletal muscle: a comparison of different modalities in preventing sarcopenia.Journal of translational medicine · 2021Review
- Bimodal right ventricular dysfunction after postnatal hyperoxia exposure: implications for the preterm heart.American journal of physiology. Heart and circulatory physiology · 2019Article
- Mitochondrial DNA alterations in aged macrophage migration inhibitory factor-knockout mice.Mechanisms of ageing and development · 2019Article
- mTORC1 underlies age-related muscle fiber damage and loss by inducing oxidative stress and catabolism.Aging cell · 2019Article
- Age-Dependent Decline in Cardiac Function in Guanidinoacetate-Frontiers in physiology · 2019Article
- Clonal expansion of mtDNA deletions: different disease models assessed by digital droplet PCR in single muscle cells.Scientific reports · 2018Article
- Effect of photobiomodulation on connective tissue remodeling and regeneration of skeletal muscle in elderly rats.Lasers in medical science · 2018Article
- The Combination of Physical Exercise with Muscle-Directed Antioxidants to Counteract Sarcopenia: A Biomedical Rationale for Pleiotropic Treatment with Creatine and Coenzyme Q10.Oxidative medicine and cellular longevity · 2017Review
- Article
- Apoptosis and necrosis mediate skeletal muscle fiber loss in age-induced mitochondrial enzymatic abnormalities.Aging cell · 2015Article
- Improvement Characteristics of Bio-active Materials Coated Fabric on Rat Muscular Mitochondria.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2015Article
- Dissecting the mechanisms underlying the accumulation of mitochondrial DNA deletions in human skeletal muscle.Human molecular genetics · 2014Article
- Perturbation of NCOA6 leads to dilated cardiomyopathy.Cell reports · 2014Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Aged muscles possess dysfunctional fibers that contain intracellular expansions of somatically derived mitochondrial DNA deletion mutations. At high abundance, these mutations disrupt the expression of mitochondrially-encoded protein subunits of the electron transport chain resulting in aerobic respiration deficient muscle fiber segments. These fiber segments atrophy and break contributing to the loss of muscle mass and function that occurs with age. By combining micro-dissection of individual muscle fibers with microarray analysis, we observed the response induced within these abnormal muscle fibers and detected an increase in many genes affecting metabolism and metabolic regulation. The transcriptional profile and subsequent protein validation suggested that a non-compensatory program of mitochondrial biogenesis was initiated. We hypothesized that this non-adaptive program of mitochondrial biogenesis was driving mtDNA deletion mutation accumulation. We tested this hypothesis by treating aged rats with β-Guanidinopropionic acid, a compound that stimulates mitochondrial biogenesis. β-Guanidinopropionic acid treatment increased muscle mitochondrial genome copy number and resulted in a 3.7 fold increase in the abundance of electron transport chain negative muscle fiber segments. We conclude that in electron transport system abnormal muscle fiber segments, a vicious cycle of metabolic insufficiency and non-compensatory mitochondrial biogenesis drive mtDNA deletion mutation accumulation.
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