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Cited by 268Muscle Physiology and DisordersMitochondrial Function and PathologyAutophagy in Disease and Therapy

Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging

Open access
Leduc-Gaudet, Jean-Philippe, Hussain, Sabah N. A., Barreiro, Esther, Gouspillou, Gilles·2021·International Journal of Molecular Sciences
DOI 10.3390/ijms22158179PMC PMC8348122
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Abstract

The maintenance of mitochondrial integrity is critical for muscle health. Mitochondria, indeed, play vital roles in a wide range of cellular processes, including energy supply, Ca2+ homeostasis, retrograde signaling, cell death, and many others. All mitochondria-containing cells, including skeletal muscle cells, dispose of several pathways to maintain mitochondrial health, including mitochondrial biogenesis, mitochondrial-derived vesicles, mitochondrial dynamics (fusion and fission process shaping mitochondrial morphology), and mitophagy—the process in charge of the removal of mitochondria though autophagy. The loss of skeletal muscle mass (atrophy) is a major health problem worldwide, especially in older people. Currently, there is no treatment to counteract the progressive decline in skeletal muscle mass and strength that occurs with aging, a process termed sarcopenia. There is increasing data, including our own, suggesting that accumulation of dysfunctional mitochondria contributes to the development of sarcopenia. Impairments in mitochondrial dynamics and mitophagy were recently proposed to contribute to sarcopenia. This review summarizes the current state of knowledge on the role played by mitochondrial dynamics and mitophagy in skeletal muscle health and in the development of sarcopenia. We also highlight recent studies showing that enhancing mitophagy in skeletal muscle is a promising therapeutic target to prevent or even treat skeletal muscle dysfunction in the elderly.

AI snapshot

Written from the paper’s full text.

TL;DR

This review argues that mitochondrial dynamics and mitophagy are critical for skeletal muscle health, and that impaired mitophagy contributes to sarcopenia. While the role of mitochondrial dynamics in aging remains unresolved because of conflicting data, enhancing mitophagy is presented as a promising therapeutic strategy.

Key findings

  • Mitochondrial fusion and fission proteins are essential for muscle health: muscle-specific deletion or knockdown of Drp1 caused 40–50% atrophy, while Mfn1/Mfn2 or Opa1 deletion produced mitochondrial dysfunction, oxidative stress, and muscle pathology.
  • The involvement of mitochondrial dynamics in sarcopenia is unclear: Mfn2 content in aged rodent muscle has been reported as decreased, unchanged, or increased, and human data for Mfn2, Opa1, and Drp1 are similarly conflicting.
  • Mitophagy is often impaired in aged skeletal muscle: the Parkin/VDAC ratio was significantly reduced in atrophied muscles of old men versus young men, and inactive old women had lower Bnip3, Beclin 1, Atg7, and Park2 expression.
  • Enhancing mitophagy improved muscle outcomes in models: Parkin overexpression increased muscle mass, fiber size, strength, mitochondrial content, and protected against oxidative stress, fibrosis, and apoptosis in old mice; urolithin A was safe and induced a molecular signature of mitochondrial health in healthy sedentary elderly individuals.

Methods

  • Design: narrative/critical review of the literature on mitochondrial dynamics, autophagy, and mitophagy in skeletal muscle health and aging.
  • Data/sample: published studies in rodents, humans, Drosophila, C. elegans, and cultured cells; no new primary data were generated.
  • Main analysis: synthesis of mechanistic and observational evidence, including loss- and gain-of-function studies, human muscle biopsy findings, and nutritional/pharmacological interventions targeting mitophagy.

Limitations

  • The paper states that conflicting data exist for mitochondrial dynamics and mitophagy in aging, that no consensus has been reached on the role of dynamics in sarcopenia, and that longitudinal human studies are needed.
  • It states that human autophagy cannot be monitored in vivo, that Parkin-dependent mitophagy knowledge is largely based on cultured cells using non-physiological uncouplers such as CCCP, and that mechanistic studies of Parkin-independent mitophagy in sarcopenia are lacking.
  • It also states that sex differences in mitochondrial dynamics during muscle aging have not been investigated and that large-scale clinical trials of mitophagy-inducing compounds are needed; evident from the text, this is a narrative review without a systematic search or meta-analysis.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/ijms22158179

Cites

177 of 177 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 188 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    The mitochondrial permeability transition pore (mPTP) becomes dysfunctional in old rodents and humans.

    “Several studies have also shown that the mitochondrial permeability transition pore (mPTP) becomes dysfunctional in old rodents and humans [9,12,13,14].”
    Quote in the paperSubstantial claim0 of 4 sources checked
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  • Interpretationreasoning

    Alterations in mPTP function contribute to the aging-related loss of muscle mass and function.

    “Alterations in mPTP function are undoubtedly contributing to the aging-related loss of muscle mass and function, since mPTP opening can trigger several atrophy-regulating pathways.”
    Quote in the paperSubstantial claim0 of 6 sources checked
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  • Premisecitation

    Aging is associated with a decline in mitochondrial bioenergetics in rodents and humans.

    “Indeed, many studies conducted in both rodents and humans have shown that aging is associated with a decline in mitochondrial bioenergetics [9,10,11].”
    Quote in the paperSubstantial claim0 of 3 sources checked
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  • Interpretationown data

    Accumulation of dysfunctional mitochondria contributes to the development of sarcopenia.

    “There is increasing data, including our own, suggesting that accumulation of dysfunctional mitochondria contributes to the development of sarcopenia.”
    Quote in the paperSubstantial claim
  • Interpretationcitation

    Mitochondrial fusion proteins are essential for the maintenance of mitochondrial and skeletal muscle health.

    “Taken altogether, the available literature clearly indicates that mitochondrial fusion proteins are essential for the maintenance of mitochondrial and skeletal muscle health.”
    Quote in the paperSubstantial claim0 of 6 sources checked
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    Premisecitation

    Exercise training and calorie restriction are the most efficient interventions to attenuate sarcopenia.

    “the most efficient interventions to attenuate sarcopenia are exercise training [21,22,23,24] and calorie restriction [25,26,27]”
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    Premisecitation

    Exercise training and calorie restriction improve mitochondrial health.

    “both well-known to improve mitochondrial health [28].”
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    • cites [28] Gouspillou, 2013, Facts and controversies in our understanding of how caloric restriction impacts the mitochondrion, Exp. Gerontol. source

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    Premisecitation

    Mfn2 content in aged rodent skeletal muscle is reported as decreased, unchanged, or increased.

    “Mfn2 content has been reported as decreased [34,49,55], unchanged [52], or even increased in aged rodent skeletal muscles [47,50,54].”
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    • cites [34] Sebastian, 2016, Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway, EMBO J. source

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    Premisecitation

    In humans, Mfn2 expression in aged skeletal muscle is reported as decreased, similar, or higher.

    “In humans, while Mfn2 expression was decreased in aged skeletal muscle in one study [60], others have reported either similar [56,58,59,61] or even higher Mfn2 content in aged skeletal muscles [61].”
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    Premisecitation

    Opa1 content normalized to complex II is lower in muscle from old sedentary individuals but not in old sportsmen.

    “Tezze et al. reported that Opa1 content normalized to complex II was lower in muscle from old sedentary individuals but not in old sportsmen.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] Tezze, 2017, Age-Associated Loss of OPA1 in Muscle Impacts Muscle Mass, Metabolic Homeostasis, Systemic Inflammation, and Epithelial Senescence, Cell Metab. source

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    Premisecitation

    Specific deletion of Opa1 in skeletal muscle leads to mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress, and inflammation.

    “Specific deletion of Opa1 in skeletal muscle leads to mitochondrial dysfunction, oxidative stress, endoplasmic reticulum (ER) stress, and inflammation [36,37,38].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [36] Tezze, 2017, Age-Associated Loss of OPA1 in Muscle Impacts Muscle Mass, Metabolic Homeostasis, Systemic Inflammation, and Epithelial Senescence, Cell Metab. source

      Not checked in the free run.

    • cites [37] Pereira, 2017, OPA1 deficiency promotes secretion of FGF21 from muscle that prevents obesity and insulin resistance, EMBO J. source

      Not checked in the free run.

    • cites [38] Rodríguez-Nuevo, A., Díaz-Ramos, A., Noguera, E., Díaz-Sáez, F., Duran, X., Muñoz, J.P., Romero, M., Plana, N., Sebastián, D., and Tezze, C. (2018). Mitochondrial DNA and TLR9 drive muscle inflammation upon Opa1 deficiency. EMBO J., 37. source

      Not checked in the free run.

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    Premisecitation

    Muscle-selective Drp1 knockdown decreases mitochondrial respiration and increases markers of muscle regeneration, denervation, fibrosis, and oxidative stress.

    “our group [43], which revealed that muscle-selective Drp1 knockdown decreases mitochondrial respiration and increases markers of muscle regeneration, denervation, fibrosis, and oxidative stress.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [43] Dulac, M., Leduc-Gaudet, J.P., Reynaud, O., Ayoub, M.B., Guerin, A., Finkelchtein, M., Hussain, S.N., and Gouspillou, G. (2020). Drp1 knockdown induces severe muscle atrophy and remodelling, mitochondrial dysfunction, autophagy impairment and denervation. J. Physiol. source

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    Premisecitation

    Mice lacking both Mfn-1 and Mfn-2 in skeletal muscle display severe mitochondrial dysfunction, accumulation of mitochondrial DNA damage, and a severe deficit in growth.

    “It was, for instance, reported that mice lacking both Mfn-1 and Mfn-2 in skeletal muscle display severe mitochondrial dysfunction, accumulation of mitochondrial DNA damage, and a severe deficit in growth [33].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [33] Chen, 2010, Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations, Cell source

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    Premisecitation

    Mfn2 deletion in skeletal muscle results in oxidative stress and muscle atrophy in adult mice.

    “Mfn2 deletion in skeletal muscle was shown to result in oxidative stress and muscle atrophy in adult mice [34].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [34] Sebastian, 2016, Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway, EMBO J. source

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    Premisecitation

    In aged rats, the oxidative soleus muscle displays signs of mitochondrial fragmentation, while the glycolytic white gastrocnemius displays signs of mitochondrial elongation with aging.

    “we recently reported in aged rats that the oxidative soleus muscle displayed signs of mitochondrial fragmentation, while the glycolytic white gastrocnemius displayed signs of mitochondrial elongation with aging [50].”
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    Interpretationcitation

    Modulation (overexpression or deletion) of proteins regulating mitochondrial dynamics in mice has either shown no benefit to muscle cells or was proven deleterious to muscle health.

    “To date, the modulation (overexpression or deletion) of proteins regulating mitochondrial dynamics in mice has either shown no benefit to muscle cells [68] or was proven deleterious to muscle health (Drp1 overexpression, Drp1 knockout, Drp1 knockdown, and Mfn1+Mfn2 knockout).”
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    Premisenone given

    Monitoring autophagy in humans in vivo is impossible, and studies in humans are restricted to assessing indirect markers of autophagy activity.

    “It is worth mentioning that monitoring autophagy in humans in vivo is impossible and that studies in humans are restricted to assessing indirect markers of autophagy activity.”
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    Premisecitation

    Autophagic flux assays are the gold standard method for assessing autophagy in a given cell or tissue.

    “Currently, autophagic flux assays are the gold standard method for assessing autophagy in a given cell or tissue [91].”
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    • cites [91] Klionsky, D.J., Abdel-Aziz, A.K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M.H., Abudu, Y.P., and Acevedo-Arozena, A. (2021). Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy, 1–382. source

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    Premisecitation

    Loss of mitochondrial membrane potential blocks the import of PINK1 into the inner mitochondrial membrane, causing PINK1 to accumulate on the outer mitochondrial membrane and stimulate recruitment of Parkin E3 ligase from the cytosol, followed by removal of damaged mitochondria by autophagosomes.

    “Loss of mitochondrial membrane potential (ΔΨm) by mitochondrial uncouplers blocks the import of PINK1 into the inner mitochondrial membrane (IMM). PINK1 then accumulates on the outer mitochondrial membrane (OMM) [122], which, in turn, stimulates the recruitment of Parkin E3 ligase activity from the cytosol followed by removal of damaged mitochondria by autophagosomes [124,125].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [122] Narendra, D.P., Jin, S.M., Tanaka, A., Suen, D.-F., Gautier, C.A., Shen, J., Cookson, M.R., and Youle, R.J. (2010). PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol., 8. source

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    Premisecitation

    Muscle-specific deletion of ATG7 in mice results in severe muscle atrophy, deterioration of neuromuscular junctions, and reduced lifespan.

    “In mice, muscle-specific deletion of ATG7 (a key regulator of autophagy) was shown to result in severe muscle atrophy, in the deterioration of neuromuscular junctions, and in a reduced lifespan [102].”
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    Premisecitation

    Mitophagy-related proteins are decreased in the skeletal muscle of old rodents, although conflicting data exist.

    “Although conflicting data exist [54,145,146,147], several studies reported that mitophagy-related proteins are decreased in the skeletal muscle of old rodents [46,120,148,149,150,151,152].”
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    Premisecitation

    Plasmid-mediated ATG7 overexpression for 14 days in aged skeletal muscles restores autophagy, ameliorates the integrity of neuromuscular junctions, and increases myofiber size.

    “Importantly, plasmid mediated-ATG7 overexpression for 14 days in aged skeletal muscles restored autophagy, ameliorated the integrity of neuromuscular junctions, and increased myofiber size [102].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [102] Carnio, 2014, Autophagy impairment in muscle induces neuromuscular junction degeneration and precocious aging, Cell Rep. source

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    Premisecitation

    Transgenic overexpression of Atg5 in mice improves motor function and extends lifespan by 17%, most likely due to enhanced autophagy.

    “Transgenic overexpression of Atg5 (key regulator of autophagy) in mice was shown to improve motor function and extend lifespan by 17%, which is most likely due to enhanced autophagy [119].”
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    Premisecitation

    p62/SQSTM1 accumulates in aged skeletal muscles, suggesting that a decline in autophagy may contribute to sarcopenia.

    “It was also reported that p62/SQSTM1 (sequestosome-1) accumulates in aged skeletal muscles, suggesting that a decline in autophagy may contribute to sarcopenia [110].”
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    Premisecitation

    Parkin overexpression increased muscle mass, fiber size, and mitochondrial enzyme activity in both young and old muscles.

    “Using gain-of-function, we recently showed that Parkin overexpression increased muscle mass, fiber size, and mitochondrial enzyme activity in both young and old muscles [152].”
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    Premisecitation

    Parkin overexpression in skeletal muscles of Drosophila led to higher mitochondrial citrate synthase enzymatic activity and attenuated the accumulation of protein aggregates.

    “In line with these findings, Parkin overexpression in skeletal muscles of Drosophila led to higher mitochondrial citrate synthase enzymatic activity and attenuated the accumulation of protein aggregates, a marker of cellular aging [156]”
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    Premisecitation

    Administration of urolithin A in the first-in-human clinical trial is safe and induces a molecular signature of mitochondrial health in the skeletal muscle of healthy sedentary elderly individuals.

    “Administration of urolithin A in the first-in-human clinical trial has also been shown to be safe and to induce a molecular signature of mitochondrial health in the skeletal muscle of healthy sedentary elderly individuals [161].”
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    Interpretationcitation

    Parkin overexpression prevents sepsis-induced skeletal muscle atrophy likely by improving mitochondrial quality and content.

    “likely by improving mitochondrial quality and content [159]”
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    Premisecitation

    In old mice, Parkin overexpression increased muscle strength, increased mitochondrial content, and protected against oxidative stress, fibrosis, and apoptosis.

    “Furthermore, in old mice, we found that Parkin overexpression increased muscle strength, increased mitochondrial content, and protected against oxidative stress, fibrosis, and apoptosis [152].”
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    • cites [152] Reynaud, 2019, Parkin overexpression protects from ageing-related loss of muscle mass and strength, J. Physiol. source

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    Premisecitation

    Tomatidine attenuates disuse-induced muscle atrophy and improves skeletal muscle mass and function in mice.

    “Another natural compound from tomatoes, tomatidine, has also been shown to attenuate disuse-induced muscle atrophy and improve skeletal muscle mass and function in mice [162], and to prolong lifespan and health span in C. elegans by stimulating mitophagy [163].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [162] Dyle, 2014, Systems-based discovery of tomatidine as a natural small molecule inhibitor of skeletal muscle atrophy, J. Biol. Chem. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Parkin loss-of-function in Drosophila resulted in decreased lifespan and increased locomotor defects.

    “whereas Parkin loss-of-function in Drosophila resulted in a decreased lifespan and increased locomotor defects [157,158].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [157] Greene, 2003, Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants, Proc. Natl. Acad. Sci. USA source

      Not checked in the free run.

    • cites [158] Pesah, 2004, Drosophila parkin mutants have decreased mass and cell size and increased sensitivity to oxygen radical stress, Development source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Urolithin A supplementation stimulates Parkin-mediated mitophagy and prolongs lifespan in C. elegans.

    “Recently, Dr Auwerx’s research group reported that urolithin A supplementation, a natural dietary microflora-derived metabolite from ingested ellagitannins and ellagic acid, stimulates Parkin-mediated mitophagy and prolongs lifespan in C. elegans [160], and improves muscle function and running performance in old rodents while increasing Parkin expression [160].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [160] Ryu, 2016, Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents, Nat. Med. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Parkin content is lower in the skeletal muscle of old mice and rats, although this is not a universal finding.

    “Similarly, and while not a universal finding [54,145,146,147], Parkin content was reported lower in the skeletal muscle of old mice [152] and rats [151].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [152] Reynaud, 2019, Parkin overexpression protects from ageing-related loss of muscle mass and strength, J. Physiol. source

      Not checked in the free run.

    • cites [151] Russ, 2014, Weakness, SR function and stress in gastrocnemius muscles of aged male rats, Exp. Gerontol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Injecting old mice with a miR-181a mimic resulted in improved skeletal muscle force, increased myofiber size, and a trend for increased succinate dehydrogenase activity.

    “Recently, it was shown that injecting old mice with a miR-181a mimic (miR-181a being a microRNA known to enhance mitophagy in myoblasts) resulted in improved skeletal muscle force, increased myofiber size, and a trend for increased succinate dehydrogenase activity [145].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [145] McCormick, 2020, miR-181a regulates p62/SQSTM1, parkin, and protein DJ-1 promoting mitochondrial dynamics in skeletal muscle aging, Aging Cell source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Urolithin A improves muscle function and running performance in old rodents while increasing Parkin expression.

    “and improves muscle function and running performance in old rodents while increasing Parkin expression [160]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [160] Ryu, 2016, Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents, Nat. Med. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Enhancing mitophagy through genetic or nutritional approaches improves skeletal muscle function in aged rodents and improves mitochondrial health in the elderly.

    “Importantly, enhancing mitophagy through genetic or nutritional approaches improves skeletal muscle function in aged rodents and improves mitochondrial health in the elderly.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Time-restricted eating has the potential to improve mitochondrial health and increase health span.

    “Interestingly, time-restricted eating, which involves regular periods of fasting, has emerged in the last few years as an intervention with the potential to improve mitochondrial health and increase health span [170,171].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [170] Longo, 2016, Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan, Cell Metab. source

      Not checked in the free run.

    • cites [171] Mattson, 2017, Impact of intermittent fasting on health and disease processes, Ageing Res. Rev. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Mitochondrial dynamics and mitophagy are critical to skeletal muscle and mitochondrial health.

    “Data from mechanistic studies have clearly highlighted that mitochondrial dynamics and mitophagy are critical to skeletal muscle and mitochondrial health.”
    Quote in the paperSubstantial claim
33 of 33

  • The paper relies on this without support.

    There is currently no treatment to counteract the progressive decline in skeletal muscle mass and strength that occurs with aging.

    “Currently, there is no treatment to counteract the progressive decline in skeletal muscle mass and strength that occurs with aging, a process termed sarcopenia.”

  • The paper relies on this without support.

    The mechanisms underlying the progressive decline in mitochondrial function in muscle aging remain poorly understood.

    “While the accumulation of mitochondrial dysfunction is now generally seen as a hallmark of muscle aging, the mechanisms underlying the progressive decline in mitochondrial function remain poorly understood.”

  • The paper relies on this without support.

    Whether enhancing or overexpressing mitochondrial fusion proteins, such as Mfn2, in muscles of aged wild-type mice can attenuate the progression of sarcopenia has never been tested.

    “Whether enhancing/overexpressing mitochondrial fusion proteins, such as Mfn2 in muscles of aged WT mice, can attenuate the progression of sarcopenia has never been tested.”

  • The paper relies on this without support.

    The molecular machinery regulating autophagy is still only partly understood.

    “However, it is important to mention here that the molecular machinery regulating autophagy is still only partly understood.”

  • The paper relies on this without support.

    Mechanistic studies assessing the role of proteins involved in Parkin-independent mitophagy in sarcopenia are currently lacking.

    “mechanistic studies aiming at assessing the role played by proteins involved in Parkin-independent mitophagy in sarcopenia are currently lacking.”

  • The paper relies on this without support.

    Physically active older adults display higher Parkin in mitochondrial fractions prepared from muscle biopsies.

    “It was also shown that physically active older adults display higher Parkin in mitochondrial fractions prepared from muscle biopsies.”
6 of 6

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Authors
Leduc-Gaudet, J.-P., Hussain, S. N. A., Barreiro, E., & Gouspillou, G.
Affiliations
  • Research Institute of the McGill University Health Centre, Department of Critical Care, Montréal, QC H4A 3J1, Canada
  • Research Institute of the McGill University Health Centre (CA)
  • Universitat Pompeu Fabra (ES)
  • Université du Québec à Montréal (CA)
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2021-07-30
Volume
22
Issue
15
Pages
8179
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms22158179
PMC
PMC8348122
OpenAlex
W3192553116
Semantic Scholar
cc362d6dc36cbd338af6217c2bd16427a49a735b
Cited by
268
References
177
Citations by year
2026: 46 · 2025: 67 · 2024: 64 · 2023: 54 · 2022: 32 · 2021: 5
FWCI
4.06
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Le dépôt institutionnel (Université du Québec à Trois-Rivières) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by)
Funders
  • Natural Sciences and Engineering Research Council of Canada (RGPIN-2021-03724)
  • Canadian Institutes of Health Research (MOP-93760, MOV-409262)
  • Spanish Ministry of Science and Innovation (FIS 18/00075, FIS 21/00215)
  • Sociedad Española de Neumología y Cirugía Torácica (SEPAR) (SEPAR 2020)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
mitochondrial dynamics, mitophagy, skeletal muscle, sarcopenia, muscle atrophy, mitochondrial fission and fusion, mitochondrial biogenesis, mitochondrial-derived vesicles, autophagy, mitochondrial dysfunction, aging, therapeutic target
MeSH terms
Aging, Animals, Humans, Mitochondria, Muscle, Muscle, Skeletal, Sarcopenia, Mitochondrial Dynamics, Mitophagy

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

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