CoChat
Sign Up
Cited by 224Nutrition and Health in AgingMuscle Physiology and DisordersMitochondrial Function and Pathology

Role of Age-Related Mitochondrial Dysfunction in Sarcopenia

Open access
Ferri, Evelyn, Marzetti, Emanuele, Calvani, Riccardo, Picca, Anna, Cesari, Matteo, Arosio, Beatrice·2020·International Journal of Molecular Sciences
DOI 10.3390/ijms21155236PMC PMC7432902
Open this paper in CoChat — free accountOpen PDF

Abstract

Skeletal muscle aging is associated with a significant loss of skeletal muscle strength and power (i.e., dynapenia), muscle mass and quality of life, a phenomenon known as sarcopenia. This condition affects nearly one-third of the older population and is one of the main factors leading to negative health outcomes in geriatric patients. Notwithstanding the exact mechanisms responsible for sarcopenia are not fully understood, mitochondria have emerged as one of the central regulators of sarcopenia. In fact, there is a wide consensus on the assumption that the loss of mitochondrial integrity in myocytes is the main factor leading to muscle degeneration. Mitochondria are also key players in senescence. It has been largely proven that the modulation of mitochondrial functions can induce the death of senescent cells and that removal of senescent cells improves musculoskeletal health, quality, and function. In this review, the crosstalk among mitochondria, cellular senescence, and sarcopenia will be discussed with the aim to elucidate the role that the musculoskeletal cellular senescence may play in the onset of sarcopenia through the mediation of mitochondria.

AI snapshot

Written from the paper’s full text.

TL;DR

This review argues that age-related mitochondrial dysfunction in skeletal myocytes is a central driver of sarcopenia and discusses crosstalk among mitochondria, cellular senescence, and muscle aging. It also highlights exercise-induced mitohormesis as a promising strategy for preserving mitochondrial function and muscle health.

Key findings

  • Sarcopenia affects nearly one-third of the older population; in inactive people, muscle mass loss can reach 1%–2% per year from age 50 to 60 and 3%–5% per year at older ages, amounting to 30%–50% loss between ages 40 and 80.
  • Mitochondrial dysfunction is implicated through accumulation of mtDNA mutations/deletions in sarcopenic muscle fibers, defective electron transport chain components, impaired ATP production, increased ROS, enhanced apoptosis, reduced PGC-1α activity, altered mitophagy, and bioenergetic decline.
  • Mitochondria also mediate cellular senescence: mitochondrial ROS are linked to telomere erosion and senescence, while senescent cells and inflammaging may impair satellite cell function and muscle regeneration; mitochondrial interventions can induce a senescent-like phenotype lacking IL-6 and IL-8.
  • Exercise training activates AMPK, SIRT1, and PGC-1α, promotes mitochondrial biogenesis and mitohormesis, and is associated with maintained low oxidative damage and prevention of sarcopenia; mtDNA copy number declines mildly with age in stimulated peripheral blood mononuclear cells from subjects aged 23–113 years, and centenarians with lower frailty have higher mtDNA molecules and fewer mtDNA deletions.

Methods

  • Narrative review summarizing available evidence on mitochondrial dysfunction, skeletal muscle aging, sarcopenia, and cellular senescence.
  • Evidence cited includes preclinical models (e.g., mtDNA-mutator mice, transgenic models) and human studies, such as droplet digital PCR measurement of mtDNA copy number in stimulated peripheral blood mononuclear cells from individuals aged 23–113 years and comparisons in centenarians by frailty.
  • No systematic search strategy, inclusion criteria, or quantitative meta-analysis is described; the synthesis is conceptual and mechanistic.

Limitations

  • The paper states that the exact mechanisms responsible for sarcopenia are not fully understood; whether mitochondrial dysfunction in muscle arises from primary organelle defects or defective quality control remains to be determined; and the contribution of systemic processes such as inflammation to muscle mitochondrial dysfunction remains to be fully elucidated.
  • Evident from the text: as a narrative review, it does not report a systematic literature search, formal quality appraisal, or quantitative synthesis, so conclusions rely on cited studies and mechanistic hypotheses.

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

Integrity signals

Registry

Crossref · 10.3390/ijms21155236

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 70 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Mitochondrial dysfunction arising from abnormal accumulation of mtDNA induced early appearance of several age-related phenotypes, including sarcopenia, in mice.

    “Previous studies showed that mitochondrial dysfunction arising from the abnormal accumulation of mitochondrial DNA (mtDNA) induced the early appearance of several age-related phenotypes, including sarcopenia, in mice [28,29,30].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [28] Kujoth, 2005, Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging, Science source

      Not checked in the free run.

    • cites [29] Trifunovic, 2004, Premature ageing in mice expressing defective mitochondrial DNA polymerase, Nature source

      Not checked in the free run.

    • cites [30] Vermulst, 2008, DNA deletions and clonal mutations drive premature aging in mitochondrial mutator mice, Nat. Genet. source

      Not checked in the free run.

  • Interpretationcitation

    Mitochondrial dysfunction (loss of mitochondrial integrity in myocytes) is a central/main pathogenetic factor in sarcopenia and muscle degeneration.

    “Notwithstanding the exact mechanisms responsible for sarcopenia are not fully understood, mitochondria have emerged as one of the central regulators of sarcopenia.”
    • Also stated in: § 1. Introduction · plain
      “Although the exact mechanisms responsible for the development and progression of sarcopenia are not fully understood, mitochondrial dysfunction has emerged as a central pathogenetic factor [23].”
    • Also stated in: § 6. Conclusions · plain
      “In this complex scenario, mitochondrial dysfunction in skeletal myocytes is recognized as a major driver of sarcopenia.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [23] Rygiel, 2016, The ageing neuromuscular system and sarcopenia: A mitochondrial perspective, J. Physiol. source

      Not checked in the free run.

    • Rests on an assumption: The exact mechanisms responsible for the development and progression of sarcopenia are not fully understood.
    • Rests on an assumption: Findings from animal models (e.g., mtDNA-mutator mice) about mitochondrial dysfunction and sarcopenia are relevant to human sarcopenia.
  • Premisecitation

    Mitochondria are key players in cellular senescence.

    “Mitochondria are also key players in senescence.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [104] Passos, J.F., Saretzki, G., Ahmed, S., Nelson, G., Richter, T., Peters, H., Wappler, I., Birket, M.J., Harold, G., and Schaeuble, K. (2007). Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence. PLoS Biol., 5. source

      Not checked in the free run.

  • Premisecitation

    With aging, PGC-1α levels dramatically fall in the skeletal muscle.

    “With aging, PGC-1α levels dramatically fall in the skeletal muscle [86], while the maintenance of PGC-1α expression preserves muscle mass during sarcopenia, cachexia, denervation, and fasting [85,87].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [86] Anderson, 2009, PGC-1alpha in aging and anti-aging interventions, Biochim. Biophys. Acta source

      Not checked in the free run.

  • Premisecitation

    Centenarians with lower levels of frailty showed a significantly higher number of mtDNA molecules and fewer mtDNA deletions compared with those with more severe frailty.

    “Interestingly, centenarians with lower levels of frailty showed a significantly higher number of mtDNA molecules and fewer mtDNA deletions compared with those with more severe frailty [37].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [37] Tedone, 2019, Quantitative mitochondrial DNA copy number determination using droplet digital PCR with single-cell resolution, Genome Res. source

      Not checked in the free run.

  • May combine two claims. 19
  • Classified as probably not a substantial claim. 3

  • May combine two claims.

    Premisecitation

    MtDNA copy number varies during aging and might be considered a biomarker that mirrors alterations within the aged human body.

    “MtDNA copy number also varies during aging and might be considered a biomarker that mirrors alterations within the aged human body [34,35,36].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [34] Pieters, 2015, Molecular responses in the telomere-mitochondrial axis of ageing in the elderly: A candidate gene approach, Mech. Ageing Dev. source

      Not checked in the free run.

    • cites [35] Qiu, 2015, The association between leukocyte telomere length and mitochondrial DNA copy number in pregnant women: A pilot study, Clin. Lab. source

      Not checked in the free run.

    • cites [36] Tyrka, 2015, Association of telomere length and mitochondrial DNA copy number in a community sample of healthy adults, Exp. Gerontol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Exercise training induces AMPK activation through the elevation of AMP/ATP ratio, which in turn induces mitochondrial biogenesis via PGC-1α activation.

    “In fact, exercise training induces AMPK activation through the elevation of AMP/ATP ratio [91], which in turn induces mitochondrial biogenesis via PGC-1α activation [92].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [91] Winder, 1996, Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise, Am. J. Physiol.

      Not checked in the free run.

    • cites [92] Jager, 2007, AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha, Proc. Natl. Acad. Sci. USA source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Despite overactivation of antioxidant pathways, a positive correlation between age and oxidative damage is well-established with advancing age.

    “However, despite the overactivation of antioxidant pathways, a positive correlation between age and oxidative damage is well-established with advancing age [33].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [33] Johnston, 2008, Resistance training, sarcopenia, and the mitochondrial theory of aging, Appl. Physiol. Nutr. Metab. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The stress imposed by exercise training is recognized as the most effective stimulus for mitochondrial biogenesis as part of redox-sensitive adaptation, resulting in enhanced mitochondrial function across the life course.

    “Indeed, the stress imposed by exercise training is recognized as the most effective stimulus for mitochondrial biogenesis as part of redox-sensitive adaptation [96,97,98], resulting in enhanced mitochondrial function across the life course [99,100].”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [96] Handy, 2012, Redox regulation of mitochondrial function, Antioxid. Redox Signal. source

      Not checked in the free run.

    • cites [97] Lee, 2000, Increase of mitochondria and mitochondrial DNA in response to oxidative stress in human cells, Biochem. J. source

      Not checked in the free run.

    • cites [98] Miotto, 2019, Exercise-induced reductions in mitochondrial ADP sensitivity contribute to the induction of gene expression and mitochondrial biogenesis through enhanced mitochondrial H2O2 emission, Mitochondrion source

      Not checked in the free run.

    • cites [99] Merry, 2016, Nuclear factor erythroid-derived 2-like 2 (NFE2L2, Nrf2) mediates exercise-induced mitochondrial biogenesis and the anti-oxidant response in mice, J. Physiol. source

      Not checked in the free run.

    • cites [100] Robinson, 2017, Enhanced Protein Translation Underlies Improved Metabolic and Physical Adaptations to Different Exercise Training Modes in Young and Old Humans, Cell Metab. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Exercise training is one of the best examples of mitohormesis, which is the phenomenon that occurs when an acute exposure to stress stimulates adaptive mitochondrial responses improving mitochondrial function and resistance to stress.

    “To date, exercise training is one of the best examples of mitohormesis, which is the phenomenon that occurs when an acute exposure to stress stimulates adaptive mitochondrial responses improving mitochondrial function and resistance to stress [101].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [101] Musci, R.V., Hamilton, K.L., and Linden, M.A. (2019). Exercise-Induced Mitohormesis for the Maintenance of Skeletal Muscle and Healthspan Extension. Sports (Basel), 7. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The accrual of mtDNA damage results in the synthesis of dysfunctional components of the electron transport chain, which in turn leads to defective ATP production and further ROS generation.

    “The accrual of mtDNA damage results in the synthesis of dysfunctional components of the electron transport chain, which in turn leads to defective ATP production and further ROS generation [31].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31] Harman, 1956, Aging: A theory based on free radical and radiation chemistry, J. Gerontol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A shift in redox status towards oxidation leads to progressive cellular decline.

    “In particular, the notion that a shift in redox status towards oxidation leading to progressive cellular decline has gained momentum [31].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] Harman, 1956, Aging: A theory based on free radical and radiation chemistry, J. Gerontol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Regular exercise tends to maintain low levels of oxidative damage and prevents sarcopenia.

    “At the same time, regular exercise tends to maintain low levels of oxidative damage and prevents sarcopenia [94].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [94] Bejma, 1999, Aging and acute exercise enhance free radical generation in rat skeletal muscle, J. Appl. Physiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    AMPK, SIRT1, and PGC-1α might act as an orchestrated network to control cellular energy expenditure and improve metabolic fitness.

    “Insights from in vivo transgenic models clearly suggest that AMPK, SIRT1, and PGC-1α might act as an orchestrated network to control cellular energy expenditure and improve metabolic fitness [84].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [84] Canto, 2009, PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure, Curr. Opin. Lipidol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In mtDNA-mutator mice, the accumulation of mtDNA mutations is associated with and, perhaps, responsible for the upregulation of apoptotic signaling in several tissues, including the muscle.

    “Notably, in mtDNA-mutator mice, the accumulation of mtDNA mutations is associated with and, perhaps, responsible for the upregulation of apoptotic signaling in several tissues, including the muscle [28].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28] Kujoth, 2005, Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging, Science source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Exercise training exerts a mitohormetic effect, positively influencing the maintenance and improvement of mitochondrial function, the antioxidant capacity, and the proteostasis.

    “This implies that exercise training exerts a mitohormetic effect, positively influencing the maintenance and improvement of mitochondrial function, the antioxidant capacity, and the proteostasis.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [101] Musci, R.V., Hamilton, K.L., and Linden, M.A. (2019). Exercise-Induced Mitohormesis for the Maintenance of Skeletal Muscle and Healthspan Extension. Sports (Basel), 7. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Several processes, both systemic and muscle-specific, have been shown to play a role in the pathogenesis of sarcopenia.

    “Several processes, both systemic and muscle-specific, have been shown to play a role in the pathogenesis of sarcopenia.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Impaired mitochondrial fission/fusion processes seem to affect the cell's ability to degrade dysfunctional mitochondria, causing ROS-induced DNA damage and senescence.

    “In particular, impaired mitochondrial fission/fusion processes seem to affect the cell’s ability to degrade dysfunctional mitochondria, causing ROS-induced DNA damage and senescence [105].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [105] Sebastian, 2016, Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway, EMBO J. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Mitochondria altered in function and morphology, and responsible for high levels of ROS, were found in senescent muscular cells.

    “Interestingly, mitochondria altered in function and morphology, and responsible for high levels of ROS, were found in senescent muscular cells [104].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [104] Passos, J.F., Saretzki, G., Ahmed, S., Nelson, G., Richter, T., Peters, H., Wappler, I., Birket, M.J., Harold, G., and Schaeuble, K. (2007). Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence. PLoS Biol., 5. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Many of these pro-inflammatory cytokines have been found to alter the gene expression program of satellite cells, deeply affecting muscle regeneration and contributing to the age-dependent decline in muscle function.

    “Many of these pro-inflammatory cytokines have been found to alter the gene expression program of satellite cells, deeply affecting muscle regeneration [116] and contributing to the age-dependent decline in muscle function [117].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [116] Pinti, 2014, Circulating mitochondrial DNA increases with age and is a familiar trait: Implications for “inflamm-aging”, Eur. J. Immunol. source

      Not checked in the free run.

    • cites [117] Habiballa, 2019, Mitochondria and cellular senescence: Implications for musculoskeletal ageing, Free Radic. Biol. Med. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    These adaptations contribute to the prevention of the age-related decline in skeletal muscle function, improving strength and muscle mass.

    “In turn, these adaptations contribute to the prevention of the age-related decline in skeletal muscle function, improving strength and muscle mass [33,101].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [33] Johnston, 2008, Resistance training, sarcopenia, and the mitochondrial theory of aging, Appl. Physiol. Nutr. Metab. source

      Not checked in the free run.

    • cites [101] Musci, R.V., Hamilton, K.L., and Linden, M.A. (2019). Exercise-Induced Mitohormesis for the Maintenance of Skeletal Muscle and Healthspan Extension. Sports (Basel), 7. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A moderate musculoskeletal inflammatory status is able to induce muscle catabolism, a phenomenon particularly enhanced in cachexia and sarcopenia.

    “Moreover, a moderate musculoskeletal inflammatory status is able to induce muscle catabolism, a phenomenon particularly enhanced in cachexia and sarcopenia [118].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [118] Zhou, 2016, Cytokine Signaling in Skeletal Muscle Wasting, Trends Endocrinol. Metab. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Age-related muscle wasting is potentially preventable and treatable.

    “Noticeably, the age-related muscle wasting is potentially preventable and treatable, which has instigated a growing interest around its pathophysiology.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Counteracting mitochondrial ROS generation, the rate of telomere shortening decelerates, the lifespan of muscular cells is extended and the muscle homeostasis is restored, delaying the onset of sarcopenia.

    “Counteracting mitochondrial ROS generation, the rate of telomere shortening decelerates, the lifespan of muscular cells is extended and the muscle homeostasis is restored [104,108,109], delaying the onset of sarcopenia.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [104] Passos, J.F., Saretzki, G., Ahmed, S., Nelson, G., Richter, T., Peters, H., Wappler, I., Birket, M.J., Harold, G., and Schaeuble, K. (2007). Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence. PLoS Biol., 5. source

      Not checked in the free run.

    • cites [108] Kang, 2006, Nicotinamide extends replicative lifespan of human cells, Aging Cell source

      Not checked in the free run.

    • cites [109] Saretzki, 2003, MitoQ counteracts telomere shortening and elongates lifespan of fibroblasts under mild oxidative stress, Aging Cell source

      Not checked in the free run.

    • Rests on an assumption: The mechanisms of cellular senescence observed in cell and animal models apply to human skeletal muscle aging.

  • May combine two claims.

    Premisecitation

    Many studies associate the presence of a great amount of mitochondrial ROS with accumulated single-strand breaks in telomere regions, thus accelerating telomere erosion and cellular senescence.

    “Many studies associate the presence of a great amount of mitochondrial ROS with accumulated single-strand breaks in telomere regions, thus accelerating telomere erosion and cellular senescence [106,107].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [106] Petersen, 1998, Preferential accumulation of single-stranded regions in telomeres of human fibroblasts, Exp. Cell Res. source

      Not checked in the free run.

    • cites [107] Pilger, 2000, Accumulation of single-strand breaks is the major cause of telomere shortening in human fibroblasts, Free Radic. Biol. Med. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Cellular senescence appeared to mainly be a consequence of telomere shortening, but this assumption has gradually been evolved by numerous studies showing that the senescent phenotype derived also from other stresses such as oxidative stress, genomic damage, and activation of inflammatory features.

    “At first, cellular senescence appeared to mainly be a consequence of the telomere shortening [102], but this assumption has gradually been evolved by numerous studies showing that the senescent phenotype derived also from other stresses such as oxidative stress, genomic damage, and activation of inflammatory features (Figure 1) [103].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [102] Bodnar, 1998, Extension of life-span by introduction of telomerase into normal human cells, Science source

      Not checked in the free run.

    • cites [103] Passos, 2015, Mitochondria: Are they causal players in cellular senescence?, Biochim. Biophys. Acta source

      Not checked in the free run.

21 of 21

  • The paper relies on this without support.

    The exact mechanisms responsible for the development and progression of sarcopenia are not fully understood.

    “Notwithstanding the exact mechanisms responsible for sarcopenia are not fully understood, mitochondria have emerged as one of the central regulators of sarcopenia.”
    “Although the exact mechanisms responsible for the development and progression of sarcopenia are not fully understood, mitochondrial dysfunction has emerged as a central pathogenetic factor [23].”

  • The paper relies on this without support.

    Findings from animal models (e.g., mtDNA-mutator mice) about mitochondrial dysfunction and sarcopenia are relevant to human sarcopenia.

    “Previous studies showed that mitochondrial dysfunction arising from the abnormal accumulation of mitochondrial DNA (mtDNA) induced the early appearance of several age-related phenotypes, including sarcopenia, in mice [28,29,30].”
    “Notably, in mtDNA-mutator mice, the accumulation of mtDNA mutations is associated with and, perhaps, responsible for the upregulation of apoptotic signaling in several tissues, including the muscle [28].”

  • The paper relies on this without support.

    Modulation of mitochondrial functions can induce the death of senescent cells.

    “It has been largely proven that the modulation of mitochondrial functions can induce the death of senescent cells”

  • The paper relies on this without support.

    Removal of senescent cells improves musculoskeletal health, quality, and function.

    “and that removal of senescent cells improves musculoskeletal health, quality, and function.”

  • The paper relies on this without support.

    The mechanisms of cellular senescence observed in cell and animal models apply to human skeletal muscle aging.

    “Interestingly, mitochondria altered in function and morphology, and responsible for high levels of ROS, were found in senescent muscular cells [104].”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Oxidative stress adversely affects muscle health through protein breakdown, inflammation, impaired regeneration, mitochondrial dysfunction, and insulin resistance.

    “Oxidative stress adversely impacts muscle health through muscle protein breakdown60, muscle inflammation61, impaired muscle regeneration62, mitochondrial dysfunction63 and insulin resistance50.”

    From Sarcopenic obesity in older adults: a clinical overview (2024) · cites this paper as [63]

  • Mitochondria perform critical functions beyond energy production to maintain homeostasis and function in skeletal myocytes, including regulation of intracellular Ca2+ homeostasis, modulation of cell proliferation, and integration of apoptotic signaling.

    “Emerging evidence suggested that apart from energy production, mitochondria perform other critical functions to maintain homeostasis and function in the skeletal myocytes, including regulation of intracellular Ca2+ homeostasis, modulation of cell proliferation, and integration of apoptotic signaling (17–19).”

    From From mitochondria to sarcopenia: role of 17β-estradiol and testosterone (2023) · cites this paper as [17]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Type II B fibers omitted from the stated type II subdivisions

    Minor

    The text says type II fibers are divided into type II A and type II X, but the next sentence identifies type II B fibers as another type.

1 of 1

The citation lists haven’t been fetched yet

References 120 · Cited by 224

Authors
Ferri, E., Marzetti, E., Calvani, R., Picca, A., Cesari, M., & Arosio, B.
Affiliations
  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
  • Università Cattolica del Sacro Cuore (IT)
  • University of Milan (IT)
Corresponding author
Ferri, Evelyn
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2020-07-23
Volume
21
Issue
15
Pages
5236
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms21155236
PMC
PMC7432902
OpenAlex
W3044803635
Semantic Scholar
78d7e8afd80c8cc96940e3e6a978e315fe3d686d
Cited by
224
References
120
Citations by year
2026: 30 · 2025: 61 · 2024: 32 · 2023: 30 · 2022: 30 · 2021: 34 · 2020: 7
FWCI
3.22
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • PubliCatt (Università Cattolica del Sacro Cuore) (submittedVersion, cc-by)
Topics
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
  • 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
Keywords
sarcopenia, mitochondrial dysfunction, skeletal muscle aging, cellular senescence, dynapenia, senolytics, muscle degeneration, older adults
MeSH terms
Aging, Humans, Mitochondria, Muscle, Cellular Senescence, Muscle, Skeletal, Sarcopenia

About these checks

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 2026-10-07.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-07.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review