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Cited by 73Mitochondrial Function and PathologyMuscle Physiology and DisordersGenetics, Aging, and Longevity in Model Organisms

Effects of Aging and Caloric Restriction on Fiber Type Composition, Mitochondrial Morphology and Dynamics in Rat Oxidative and Glycolytic Muscles

Open access
Faitg, Julie, Leduc-Gaudet, Jean-Philippe, Reynaud, Olivier, Ferland, Guylaine, Gaudreau, Pierrette, Gouspillou, Gilles·2019·Frontiers in Physiology
DOI 10.3389/fphys.2019.00420PMC PMC6503296
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Abstract

Aging is associated with a progressive decline in muscle mass and strength, a process known as sarcopenia. Evidence indicates that mitochondrial dysfunction plays a causal role in sarcopenia and suggests that alterations in mitochondrial dynamics/morphology may represent an underlying mechanism. Caloric restriction (CR) is amongst the most efficient non-pharmacological interventions to attenuate sarcopenia in rodents and is thought to exert its beneficial effects by improving mitochondrial function. However, CR effects on mitochondrial morphology and dynamics, especially in aging muscle, remain unknown. To address this issue, we investigated mitochondrial morphology and dynamics in the oxidative soleus (SOL) and glycolytic white gastrocnemius (WG) muscles of adult (9-month-old) ad libitum-fed (AL; A-AL), old (22-month-old) AL-fed (O-AL) and old CR (O-CR) rats. We show that CR attenuates the aging-related decline in the muscle-to-body-weight ratio, a sarcopenic index. CR also prevented the effects of aging on muscle fiber type composition in both muscles. With aging, the SOL displayed fragmented SubSarcolemmal (SS) and InterMyoFibrillar (IMF) mitochondria, an effect attenuated by CR. Aged WG displayed enlarged SS and more complex/branched IMF mitochondria. CR had marginal anti-aging effects on WG mitochondrial morphology. In the SOL, DRP1 (pro-fission protein) content was higher in O-AL vs YA-AL and Mfn2 (pro-fusion) content was higher in O-CR vs A-AL. In the gastrocnemius, Mfn2, Drp1 and Fis1 (pro-fission) contents were higher in O-AL vs A-AL. CR reduced this aging-related increase in Mfn2 and Fis1 content. Overall, these results reveal for the first time that aging differentially impacts mitochondrial morphology and dynamics in different muscle fiber types, by increasing fission/fragmentation in oxidative fibers while enhancing mitochondrial size and branching in glycolytic fibers. Our results also indicate that although CR partially attenuates aging-related changes in mitochondrial dynamics in glycolytic fibers, its anti-aging effect on mitochondrial morphology is restricted to oxidative fibers.

AI snapshot

Written from the paper’s full text.

TL;DR

Aging differentially alters mitochondrial morphology and dynamics in rat oxidative vs glycolytic muscle: soleus shows fission/fragmentation, while white gastrocnemius shows enlarged and more branched mitochondria. Caloric restriction largely protects mitochondrial morphology in oxidative soleus but has marginal anti-aging effects in glycolytic white gastrocnemius.

Key findings

  • CR attenuated the aging-related decline in the muscle-to-body-weight ratio: O-CR rats had significantly higher TA, GAS, and PL normalized weights than O-AL rats, with no difference between O-CR and A-AL. CR also prevented aging effects on fiber type composition in both soleus and gastrocnemius.
  • In oxidative soleus, O-AL displayed fragmented subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria, an effect attenuated by CR. In glycolytic white gastrocnemius, O-AL displayed enlarged SS mitochondria and more complex/branched IMF mitochondria; CR had marginal anti-aging effects on WG mitochondrial morphology.
  • Mitochondrial volume density did not differ among A-AL, O-AL, and O-CR in either muscle, but SDH activity was lower in O-AL soleus and gastrocnemius. CR restored gastrocnemius SDH activity to A-AL levels but did not protect soleus SDH activity.
  • In soleus, Drp1 content was higher in O-AL vs A-AL, and Mfn2 content was higher in O-CR vs A-AL. In gastrocnemius, Mfn2, Drp1, and Fis1 contents were higher in O-AL vs A-AL; CR reduced the aging-related increase in Mfn2 and Fis1.

Methods

  • Male Sprague–Dawley rats: adult ad libitum-fed (A-AL, 9 months, n = 9), old ad libitum-fed (O-AL, 22 months, n = 4), and old caloric-restricted (O-CR, 22 months, n = 11). CR began at 8 months with 20% restriction for 2 weeks followed by 40% CR for 13 months.
  • Soleus and white gastrocnemius were analyzed by transmission electron microscopy for SS and IMF mitochondrial morphology/shape descriptors; TEM tracing used n = 4 per group. Fiber typing used MHC immunolabeling, mitochondrial content was assessed by TEM volume density, SDH activity was measured in situ, and Mfn2, Drp1, and Fis1 were quantified by immunoblotting.
  • Statistics used one-way or two-way ANOVA with Benjamini–Krieger–Yekutieli post hoc correction (p < 0.05, q < 0.1) and Kolmogorov–Smirnov tests for distribution comparisons.

Limitations

  • The paper does not include a dedicated limitations section. It states that muscle contractility was not assessed and that mechanistic studies are needed to test whether changes in mitochondrial dynamics are causal.
  • Evident from the text: the O-AL group was small (n = 4, described as all available O-AL rats), and TEM morphology analyses used n = 4 per group, though the authors note n = 3–4 is common in TEM-based mitochondrial morphology studies.
  • Evident from the text: mitochondrial morphology was assessed using a 2-dimensional TEM approach, and protein content changes are correlative rather than direct measures of fusion/fission flux.

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

Integrity signals

Registry

Crossref · 10.3389/fphys.2019.00420

Cites

57 of 57 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 48 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Aging is associated with fragmentation of IMF mitochondria in the SOL.

    “With aging, the SOL displayed fragmented SubSarcolemmal (SS) and InterMyoFibrillar (IMF) mitochondria, an effect attenuated by CR.”
    • Also stated in: § Effect of Aging and Caloric Restriction on Skeletal Muscle Mitochondrial Morphology · plain
      “As shown in Figure 5 and Table 1, the average values and frequency distribution of all of the shape descriptors quantified indicate that SOL IMF mitochondria from O-AL rats are fragmented compared to A-AL animals.”
    Quote in the paperSubstantial claim
  • Findingown data

    Aging is associated with fragmentation of SS mitochondria in the SOL.

    “With aging, the SOL displayed fragmented SubSarcolemmal (SS) and InterMyoFibrillar (IMF) mitochondria, an effect attenuated by CR.”
    • Also stated in: § Effect of Aging and Caloric Restriction on Skeletal Muscle Mitochondrial Morphology · hedged
      “Taken altogether, the data indicate that aging is associated with a fragmentation of SS mitochondria in the SOL.”
    Quote in the paperSubstantial claim
  • Findingown data

    Aged WG displays enlarged SS mitochondria.

    “Aged WG displayed enlarged SS and more complex/branched IMF mitochondria.”
    • Also stated in: § Effect of Aging and Caloric Restriction on Skeletal Muscle Mitochondrial Morphology · hedged
      “These data associated, with the respective increase and decrease in the proportion of complex and simple SS mitochondria in the WG of O-AL vs A-AL (Figures 6C,D), indicate that old animals display enlarged and more complex SS mitochondria in the WG.”
    Quote in the paperSubstantial claim
  • Findingown data

    CR attenuates the aging-related decline in the muscle-to-body-weight ratio, a sarcopenic index.

    “We show that CR attenuates the aging-related decline in the muscle-to-body-weight ratio, a sarcopenic index.”
    • Also stated in: § Effect of Aging and Caloric Restriction on Body and Muscles Weights · hedged
      “suggesting that CR prevented the aging-related loss of relative muscle mass.”
    Quote in the paperSubstantial claim
  • Findingown data

    In the gastrocnemius, Drp1 content is higher in O-AL vs A-AL.

    “In the gastrocnemius, Mfn2, Drp1, and Fis1 (pro-fission) contents were higher in O-AL vs A-AL.”
    Quote in the paperSubstantial claim
  • May combine two claims. 28
  • Classified as probably not a substantial claim. 13

  • May combine two claims.

    Findingown data

    Compared to O-AL, SOL from O-CR displayed SS mitochondria with lower average circularity values, higher average form factor, a shift to the left of the circularity distribution, and a shift to the right of the distribution of form factor values.

    “As compared to O-AL, SOL from O-CR displayed SS mitochondria with lower average circularity values, higher average form factor (Table 1), as well as a shift to the left of the circularity distribution and a shift to the right of the distribution of form factor values (Figure 4B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In transversal orientation, CR did not prevent the effects of aging on all shape descriptors and even exacerbated some differences between O-AL and A-AL.

    “In line with the data obtained in longitudinal orientation, data in transversal orientation indicate that CR did not prevent the effects of aging on all shape descriptors and even exacerbated some differences between O-AL and A-AL (Figure 7B and Table 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    SS mitochondria from O-AL SOL displayed significantly higher average circularity value, a shift to right of the circularity distribution, and a shift to the left of the distribution of form factor and aspect ratio values vs A-AL.

    “However, SS mitochondria from O-AL SOL displayed significantly higher average circularity value (Table 1), a shift to right of the circularity distribution and a shift to the left of the distribution of form factor and aspect ratio values vs A-AL (Figure 4B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In SOL, O-CR displays higher Drp1 content vs A-AL, and Mfn2 level is significantly higher in O-CR vs A-AL, while no difference is observed between O-CR and A-AL for Fis1 content.

    “Surprisingly, O-CR displayed higher Drp1 content vs A-AL (Figures 8A,B).”
    • Also stated in: § Effects of Aging and Caloric Restriction on Immunoreactive Levels of Proteins Regulating Mitochondrial Dynamics · plain
      “While no difference was observed between O-CR and A-AL for Fis1 content, the Mfn2 level was significantly higher in the SOL of O-CR vs A-AL (Figures 8A,B).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Proportions of type I and type IIa fibers in SOL were respectively higher and lower in O-AL and O-CR vs A-AL.

    “The proportions of type I and type IIa fibers in the SOL were respectively higher and lower in O-AL and O-CR vs A-AL (Figure 2G).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In SOL, Drp1 immunoreactive levels are significantly higher in O-AL vs A-AL, while no difference is observed between O-AL and A-AL for Mfn2 and Fis1 contents.

    “As shown in Figures 8A,B, the immunoreactive levels of the pro-fission protein Drp1 were significantly higher in the SOL of O-AL vs A-AL, while no difference was observed between O-AL and A-AL for the contents of Mfn2 and Fis1.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In transversal orientation, IMF mitochondria from O-AL rats have higher form factor values and complex shifts in the distribution of aspect ratio and form factor values vs A-AL.

    “However, IMF mitochondria from O-AL rats in transversal orientation displayed higher form factor values and complex shifts in the distribution of aspect ratio and form factor values vs A-AL (Figure 7A and Table 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In both transversal and longitudinal orientations, O-AL displayed an increase in the proportion of morphologically simple mitochondria vs A-AL, a difference attenuated in O-CR animals.

    “In both transversal and longitudinal orientations, O-AL displayed an increase in the proportion of morphologically simple mitochondria vs A-AL, a difference attenuated in O-CR animals (Figures 4C,D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    O-CR displayed significantly lower type I and IIx fiber proportion and higher type IIb fiber proportion vs O-AL.

    “Importantly, O-CR displayed significantly lower type I and IIx fiber proportion and higher type IIb fiber proportion vs O-AL (Figure 2H).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    O-AL rats displayed a decrease in type IIa fiber proportion in the SOL and a shift toward more oxidative fibers in the GAS.

    “Indeed, O-AL rats displayed a decrease in type IIa fiber proportion in the SOL and a shift toward more oxidative fibers in the GAS.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Proportions of type I and IIa fibers were respectively lower and higher in SOL of O-CR vs O-AL.

    “Interestingly, the proportions of type I and IIa fibers were respectively lower and higher in the SOL of O-CR vs O-AL (Figure 2G).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    CR did not attenuate the effects of aging on IMF mitochondrial shape descriptors in longitudinal orientation; CR exacerbated the differences between O-AL and A-AL.

    “CR did not attenuate the effects of aging on these shape descriptors in longitudinal orientation; CR even exacerbated the differences between O-AL and A-AL (Figure 7A and Table 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In longitudinal orientation, IMF mitochondria from O-AL rats have significantly higher area, perimeter, aspect ratio, form factor, and minimum Feret diameter and lower circularity vs A-AL.

    “When we analyzed in longitudinal orientation, IMF mitochondria from O-AL rats displayed significantly higher area, perimeter, aspect ratio, form factor, and minimum Feret diameter vs A-AL (Figure 7A and Table 2) and lower circularity values vs A-AL (Figure 7A and Table 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Aged WG muscles display a higher proportion of enlarged and less circular SS mitochondria and a higher proportion of more complex, elongated, and branched mitochondria.

    “Overall, these results indicate that aged WG muscles display a higher proportion of enlarged and less circular SS mitochondria and a higher proportion of more complex, elongated, and branched mitochondria.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    O-AL group displayed significantly higher type I and IIx fiber proportion in GAS and lower type IIb proportion vs A-AL.

    “O-AL group displayed significantly higher type I and IIx fiber proportion in the GAS and lower type IIb proportion vs A-AL (Figure 2H).”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Mfn-1 and -2 deletion in skeletal muscle of young animals leads to abnormal mitochondrial morphology, severe mitochondrial dysfunction, and a severe deficit in muscle growth.

    “It was for instance shown in skeletal muscle of young animals that Mfn-1 and -2 deletion leads to abnormal mitochondrial morphology, severe mitochondrial dysfunction, and a severe deficit in muscle growth (Chen et al., 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Chen et al., 2010 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    CR is thought to exert its effects mostly by improving mitochondria.

    “Long-term caloric restriction (CR) is among the most efficient interventions to offset sarcopenia in rodents, and CR is thought to exert its effects mostly through by improving mitochondria (see (Gouspillou and Hepple, 2013) for review).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Gouspillou and Hepple, 2013

      Not checked in the free run.

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

    Premisecitation

    In most cell types, and particularly in skeletal muscle, mitochondria display a complex and dynamic architecture.

    “In most cell types, and particularly in skeletal muscle (Ogata and Yamasaki, 1997), mitochondria display a complex and dynamic architecture.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ogata and Yamasaki, 1997

      Not checked in the free run.

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

    Premisecitation

    CR reduces markers of apoptosis in aged rat skeletal muscle.

    “CR has also been shown to reduce markers of apoptosis in aged rat skeletal muscle (Wohlgemuth et al., 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Wohlgemuth et al., 2010 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Mitochondrial morphology and function are interrelated, with changes in mitochondrial morphology affecting mitochondrial function and vice versa.

    “This is of particular importance since it is now established that mitochondrial morphology and function are interrelated, with changes in mitochondrial morphology affecting mitochondrial function (Chen et al., 2005; Jahani-Asl et al., 2007; Yu et al., 2008; Ong et al., 2010; Gomes et al., 2011) and vice versa (Benard et al., 2007).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Chen et al., 2005 source

      Not checked in the free run.

    • cites Jahani-Asl et al., 2007

      Not checked in the free run.

    • cites Yu et al., 2008

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Mitochondria form a dynamic network with the ability to undergo fusion and fission events.

    “Indeed, mitochondria form a dynamic network, with the ability to undergo fusion and fission events, processes collectively known as mitochondrial dynamics (Chan, 2006), which are regulated by Mitofusins 1 & 2 (Mfn 1 & 2) and OPtic Atrophy 1 (OPA-1) and Dynamin-Related Protein 1 (DRP1) and mitochondrial-FISsion 1 protein (FIS1) proteins, respectively (Chan, 2006).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Chan, 2006 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Aging is associated with a progressive decline in muscle mass and strength, a process known as sarcopenia.

    “Skeletal muscle aging is associated with a progressive decline in muscle mass and function, a biological process known as sarcopenia (Rosenberg, 1997).”
    • Also stated in: § Abstract · plain
      “Aging is associated with a progressive decline in muscle mass and strength, a process known as sarcopenia.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rosenberg, 1997 source

      Not checked in the free run.

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

    Premisecitation

    CR decreases mitochondrial reactive oxygen species production.

    “Indeed, CR has been shown to decrease mitochondrial reactive oxygen species (ROS) production (Asami et al., 2008; Lanza et al., 2012), increase mitochondrial coupling efficiency (Lanza et al., 2012), and increase mitochondrial respiration per unit of mitochondria in aged muscles (Hepple et al., 2005, 2006).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Asami et al., 2008

      Not checked in the free run.

    • cites Lanza et al., 2012 source

      Not checked in the free run.

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

    Premisecitation

    Mitochondrial fusion and fission are regulated by Mfn1&2, OPA1, DRP1, and FIS1 proteins.

    “Indeed, mitochondria form a dynamic network, with the ability to undergo fusion and fission events, processes collectively known as mitochondrial dynamics (Chan, 2006), which are regulated by Mitofusins 1 & 2 (Mfn 1 & 2) and OPtic Atrophy 1 (OPA-1) and Dynamin-Related Protein 1 (DRP1) and mitochondrial-FISsion 1 protein (FIS1) proteins, respectively (Chan, 2006).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Chan, 2006 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    CR increases mitochondrial coupling efficiency.

    “Indeed, CR has been shown to decrease mitochondrial reactive oxygen species (ROS) production (Asami et al., 2008; Lanza et al., 2012), increase mitochondrial coupling efficiency (Lanza et al., 2012), and increase mitochondrial respiration per unit of mitochondria in aged muscles (Hepple et al., 2005, 2006).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Lanza et al., 2012 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Neither aging nor CR affected mitochondrial content.

    “These results indicate that neither aging nor CR affected mitochondrial content.”
    Quote in the paperSubstantial claim

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

    Study design and conductreasoning

    O-CR animals received a diet enriched in vitamins and minerals to ensure that both groups received comparable amounts of micronutrients.

    “At that stage, which corresponds to the start of the CR regimen, O-CR animals received a diet enriched in vitamins and minerals (TD.130771) to ensure that both groups received comparable amounts of micronutrients.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    CR partially attenuated the impact of aging on mitochondrial dynamics in the GAS and might have exerted a pro-fusion impact in the SOL.

    “They also indicate that CR partially attenuated the impact of aging on mitochondrial dynamics in the GAS and might have exerted a pro-fusion impact in the SOL.”
    Quote in the paperSubstantial claim

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

    Study design and conductcitation

    n = 3-4 is a sample size commonly used in TEM-based studies investigating mitochondrial morphology and ultrastructure.

    “It is important to highlight here that n = 3–4 is a sample size commonly used in TEM-based studies investigating mitochondrial morphology and ultrastructure (Bonnard et al., 2008; Sato et al., 2013; Arruda et al., 2014; Leduc-Gaudet et al., 2015; Saleem et al., 2015; Demeter-Haludka et al., 2018; Loro et al., 2018).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Bonnard et al., 2008 source

      Not checked in the free run.

    • cites Sato et al., 2013

      Not checked in the free run.

    • cites Arruda et al., 2014

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    CR attenuated this aging-related fragmentation of SS and IMF mitochondria in the SOL but had little to no impact on mitochondrial morphology in the WG.

    “We also show that CR attenuated this aging-related fragmentation of SS and IMF mitochondria in the SOL but had little to no impact on mitochondrial morphology in the WG.”
    Quote in the paperSubstantial claim

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

    Study design and conductreasoning

    All samples for each species were processed at the same time and using the same incubation solution, ensuring that all samples underwent the exact same experimental conditions.

    “All samples for each species were processed at the same time and using the same incubation solution, ensuring that all samples underwent the exact same experimental conditions.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Aging in the highly glycolytic WG is associated with an enlargement of SS mitochondria and an increase in the complexity and branching of IMF mitochondria.

    “In contrast, we found that aging in the highly glycolytic WG is associated with an enlargement of SS mitochondria and an increase in the complexity and branching of IMF mitochondria.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Aging increases mitochondrial fission in the SOL while increasing both mitochondrial fission and fusion in the GAS.

    “Taken altogether, our data indicate that aging increases mitochondrial fission in the SOL while increasing both mitochondrial fission and fusion in the GAS.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    All animal procedures were approved by the Comité Institutionnel de Protection des Animaux de l'UQAM and the Centre de recherche de l'hôpital du Sacré-Coeur de Montréal.

    “All animal procedures were approved by the Comité Institutionnel de Protection des Animaux de l’UQAM (#CIPA875) and the Centre de recherche de l’hôpital du Sacré-Coeur de Montréal (#FRSQ.01) in compliance with the guidelines of the Canadian Council on Animal Care.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    CR seems to protect against the effect of aging on mitochondrial morphology in the SOL, but had minor or no anti-aging effect on mitochondrial morphology in the glycolytic WG.

    “In addition, our results highlight that while CR seems to protect against the effect of aging on mitochondrial morphology in the SOL, it had minor or no anti-aging effect on mitochondrial morphology in the glycolytic WG.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    CR partially attenuates aging-related changes in the content of proteins regulating mitochondrial dynamics in glycolytic fibers, but its anti-aging effect on mitochondrial morphology is restricted to oxidative fibers.

    “Our results also indicate that although CR partially attenuates aging-related changes in the content of proteins regulating mitochondrial dynamics in glycolytic fibers, its anti-aging effect on mitochondrial morphology is restricted to oxidative fibers.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Oxidative fibers display increased mitochondrial fission/fragmentation, and glycolytic fibers display increased mitochondrial size and branching.

    “Indeed, we show that oxidative fibers display increased mitochondrial fission/fragmentation, and glycolytic fibers display increased mitochondrial size and branching.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    IMF mitochondria are tubular and branched structures that align along the sarcomeric plan (in transverse orientation), which essentially appear as round structures when visualized in longitudinal orientation.

    “This is because IMF mitochondria are tubular and branched structures that align along the sarcomeric plan (in transverse orientation) (Ogata and Yamasaki, 1997), which essentially appear as round structures when visualized in longitudinal orientation (Gouspillou et al., 2013).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Ogata and Yamasaki, 1997

      Not checked in the free run.

    • cites Gouspillou et al., 2013

      Not checked in the free run.

38 of 38

  • The paper relies on this without support.

    The effects of CR on mitochondrial morphology and dynamics in aging muscle were unknown before this study.

    “However, CR effects on mitochondrial morphology and dynamics, especially in aging muscle, remain unknown.”

  • The paper relies on this without support.

    The impact of CR on mitochondrial dynamics and morphology had never been investigated in adult and old muscles.

    “Thus, the impact of CR on mitochondrial dynamics and morphology has never been investigated in adult and old muscles.”

  • The paper relies on this without support.

    The effects of aging on mitochondrial morphology and dynamics in skeletal muscle were unclear, and those of CR were currently unknown.

    “However, to date, the effects of aging on mitochondrial morphology and dynamics in skeletal muscle remain unclear, and those of CR are currently unknown.”

  • The paper relies on this without support.

    Many of the effects of CR, specifically on mitochondrial biology, in aging muscles, remain to be studied.

    “However, many of the effects of CR, specifically on mitochondrial biology, in aging muscles, remain to be studied.”

  • The authors state this as an assumption.

    No previous study has compared the impact of aging and caloric restriction on both oxidative and glycolytic muscles.

    “In addition, to our knowledge, no previous study has compared the impact of aging and CR, on both oxidative and glycolytic muscles.”
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?

  • Alterations in mitochondrial distribution, morphology, and function are present in atrophic muscles in aging, muscle disuse, burn injury, intensive care unit-acquired weakness, insulin resistance, chronic obstructive pulmonary disease, cancer cachexia, and different neuromuscular disorders.

    “Alterations in mitochondrial distribution, morphology, and function are present in atrophic muscles in aging [148–150], muscle disuse [151, 152], burn injury [153], intensive care unit-acquired weakness [154], insulin resistance [155] chronic obstructive pulmonary disease (COPD) [156], cancer cachexia [157–159], and different neuromuscular disorders [160].”

    From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [150]

  • Several studies did not detect any impact of aging on Opa1 content in skeletal muscle of aged mice, rats, and humans.

    “However, several studies did not detect any impact of aging on Opa1 content in the skeletal muscle of aged mice [52,54], rats [50], and humans [57,58].”

    From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [50]

  • 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].”

    From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [50]

  • Studies in rodents have reported increased or unchanged Drp1 content in aged skeletal muscles.

    “Indeed, studies in rodents have reported increased [49,50,51] or unchanged [34,47,52,54] Drp1 content in aged skeletal muscles.”

    From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [50]

  • 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].”

    From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [50]

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.

  • CR did not fully prevent soleus fiber-type changes

    Major

    The Results state that O-CR rats still had higher type I and lower type IIa fiber proportions than A-AL rats in the soleus. That contradicts the Discussion's claim that there was no difference in fiber-type composition between those groups.

  • CR attenuated several longitudinal WG mitochondrial changes

    Minor

    The claim that CR did not attenuate the longitudinal IMF shape changes conflicts with Table 2. For example, the aspect ratio was 1.63 in A-AL, rose to 1.97 in O-AL, and fell significantly to 1.81 in O-CR; circularity and form factor also moved significantly toward A-AL values.

  • Not all soleus IMF shape descriptors indicate fragmentation

    Minor

    The statement that all quantified shape descriptors indicate fragmentation overstates Table 1. In longitudinal orientation, O-AL IMF mitochondria have significantly greater area than A-AL mitochondria (0.11 versus 0.10), rather than smaller area.

3 of 3

Cites

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1 of the 58 references couldn’t be matched to a known paper.

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Authors
Faitg, J., Leduc-Gaudet, J.-P., Reynaud, O., Ferland, G., Gaudreau, P., & Gouspillou, G.
Affiliations
  • Université du Québec à Montréal (CA)
  • Montreal Heart Institute (CA)
  • Centre Hospitalier de l’Université de Montréal (CA)
  • Institut Universitaire de Gériatrie de Montréal (CA)
Corresponding author
Gouspillou, Gilles
ORCID
Venue
Frontiers in Physiology
Publisher
Frontiers Media SA
Published
2019-04-24
Volume
10
Pages
420-420
ISSN
1664-042X (ISSN-L)
DOI
10.3389/fphys.2019.00420
PMC
PMC6503296
OpenAlex
W2942870682
Cited by
72
References
58
Citations by year
2026: 7 · 2025: 8 · 2024: 10 · 2023: 12 · 2022: 13 · 2021: 14 · 2020: 7 · 2019: 1
FWCI
2.89
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Physiology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Archipel (Université du Québec à Montréal) (acceptedVersion)
  • Le dépôt institutionnel (Université du Québec à Trois-Rivières) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Canadian Institutes of Health Research
  • Natural Sciences and Engineering Research Council of Canada (RGPIN-2014, RGPIN-2014-04668)
  • Fonds de Recherche du Québec - Santé (FRQS‐35184, Junior 1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
aging, caloric restriction, sarcopenia, mitochondrial dynamics, mitochondrial morphology, muscle fiber composition, oxidative muscle, glycolytic muscle, soleus muscle, Drp1, mitofusin 2, Fis1, mitochondrial fission, mitochondrial fusion

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 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

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 ›

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