Aging promotes an increase in mitochondrial fragmentation in astrocytes

Classified as probably not a substantial claim.

Phosphorylation of DRP1 at serine 616 activates DRP1-mediated mitochondrial fission and its localization on the outer membrane.

“It is well established that phosphorylation of DRP1 at the serine 616 (S616) site activates DRP1-mediated mitochondrial fission and its localization on the outer membrane (Taguchi et al., 2007; Bo et al., 2018).”

• cites Taguchi et al., 2007 sourcePartly supported

  The section on mitochondrial fragmentation reports that phosphorylation at rat Drp1 Ser-585 stimulates mitochondrial fission in mitotic cells. It identifies the corresponding site as Ser-590 in human Drp1 isoform 2, not Ser-616, and does not show that phosphorylation promotes Drp1 localization on the outer mitochondrial membrane. The Discussion says the mechanism by which phosphorylation stimulates fission remains unknown. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites Bo et al., 2018Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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

Primary senescent astrocytes from rats induce loss of mitochondrial membrane potential and alter mitochondrial dynamics in cortical neurons.

“In addition to this finding, primary senescent astrocytes from rats induce loss of mitochondrial membrane potential and alter mitochondrial dynamics in cortical neurons (Morales-Rosales et al., 2021).”

• cites Morales-Rosales et al., 2021 sourceSupported

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

Astrocytic synaptogenic capacity and promotion of neurite growth are reduced in senescent astrocytes.

“Our group demonstrates that astrocytic synaptogenic capacity and promotion of neurite growth are reduced in senescent astrocytes (Matias et al., 2022).”

• cites Matias et al., 2022 sourceSupported

May combine two claims.

Glycogen granules are a feature unique to astrocytes in the brain and can be used to identify astrocytes in electron microscopy.

“The mitochondria analyzed were exclusively from cells containing glycogen granules in the cytoplasm, a feature unique to astrocytes in the brain. In electron microscopy images, glycogen appears as electron-dense, spherical granules within astrocytic processes (Phelps, 1972; Vezzoli et al., 2020).”

• cites Phelps, 1972 sourceNot checked — no full text of the source
• cites Vezzoli et al., 2020 sourceSupported

Classified as probably not a substantial claim.

Mitochondria with an aspect ratio >2 are considered long mitochondria.

“Mitochondria with a ratio of >2 were considered as long mitochondria (long-mito), as previously described (Zhang et al., 2016; Wen et al., 2022).”

• cites Zhang et al., 2016 sourceCould not verify

  The Results describe mitochondria as elongated, and the Introduction discusses elongated mitochondrial networks, but neither gives an aspect-ratio cutoff. Searches for “aspect ratio” and a long-versus-short threshold of 2 found no passage establishing the claimed classification in our copy. (LLM, conf=0.75)

  Experimental — accuracy not yet measured
• cites Wen et al., 2022 sourceSupported

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

Downregulation of MFN1 and OPA1 also suppressed the radiation-induced increase in doubling time of human fibroblasts.

“Downregulation of MFN1 and OPA1 also suppressed the radiation-induced increase in doubling time of human fibroblasts (Son et al., 2017).”

• cites Son et al., 2017 sourceSupported

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

The anti-aging effects of DRP1 require functional mitophagy, which is typically compromised in the aging brain.

“the anti-aging effects of DRP1 require functional mitophagy, which is typically compromised in the aging brain (Caponio et al., 2022).”

• cites Caponio et al., 2022 sourcePartly supported

  The ‘Impaired autophagy and mitophagy in normal ageing brain’ section reports that Drp1 overexpression increased lifespan in flies and that evidence from human post-mortem brains reflects mitophagy dysfunction with ageing. It does not establish that Drp1’s lifespan benefit requires functional mitophagy; the reported Drp1 result is also in flies, not the ageing human brain. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Classified as probably not a substantial claim.

The parameters used for mitochondrial morphology analysis have been previously validated in the literature.

“The utilization of these parameters has been previously validated in the literature using well-characterized mediators of mitochondrial fission and fusion.”

• cites Dagda et al., 2009 sourceSupported
• cites Wiemerslage and Lee, 2016 sourceSupported

May combine two claims.

Glycogen granules are exclusive to astrocytes within the central nervous system and serve as an energy reserve.

“Glycogen granules are exclusive to astrocytes within the central nervous system and serve as an energy reserve, particularly important in regulating neuronal metabolismo (Phelps, 1972; Vezzoli et al., 2020)”

• cites Phelps, 1972 sourceNot checked — no full text of the source
• cites Vezzoli et al., 2020 sourceSupported

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

In neurodegenerative diseases such as Alzheimer's and Parkinson's, mitochondrial fragmentation is often observed in affected neurons.

“In the context of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, mitochondrial fragmentation is often observed in affected neurons (Wang et al., 2017; Wang et al., 2020).”

• cites Wang et al., 2017 sourcePartly supported

  The Discussion reports significant mitochondrial fragmentation in hippocampal and cortical neurons of CRND8 mice, an Alzheimer’s disease model, and describes similar findings in Alzheimer’s neuronal cell models. It does not establish the same observation in Parkinson’s disease neurons; the only Parkinson’s disease mention found is a reference-list entry. The claim also generalizes beyond the models studied. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites Wang et al., 2020 sourcePartly supported

  The section “Abnormal mitochondrial fusion and fission in AD” (page unavailable) describes evidence of fragmented mitochondria in susceptible neurons from Alzheimer’s disease brain tissue. The paper mentions Parkinson’s disease in connection with ER–mitochondria tethering, but does not report mitochondrial fragmentation in affected Parkinson’s neurons. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

Genetic knockdown of MFN1 and OPA1 in old normal human fibroblasts decreased the oxygen consumption rate and shifted metabolism toward glycolysis.

“Genetic knockdown of MFN1 and OPA1 in old normal human fibroblasts decreased the oxygen consumption rate and shifted metabolism toward glycolysis.”

• cites Son et al., 2017 sourceSupported

May combine two claims.

With advancing age, alterations in mitochondrial dynamics occur in the brain, characterized by increased mitochondrial fragmentation and impaired mitochondrial fusion.

“With advancing age, alterations in mitochondrial dynamics occur in the brain, characterized by increased mitochondrial fragmentation and impaired mitochondrial fusion.”

• cites Joshi et al., 2019 sourcePartly supported

  The introductory passage labeled Abstract (page unavailable) describes excessive mitochondrial fragmentation in neurons with neurodegenerative diseases, and the Discussion describes increased fission in activated microglia. Neither passage establishes that fragmentation increases with normal advancing age or that mitochondrial fusion becomes impaired; searches for aging and fusion did not find those claims. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites Bantle et al., 2020 sourcePartly supported

  The Introduction (page unavailable) says mitochondrial dysfunction is a hallmark of aging. The section on astrocyte inflammatory activation discusses possible mitochondrial fragmentation from PINK1 or Parkin mutations, not from aging; our copy does not establish age-related fragmentation or impaired fusion in the brain. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

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

Positive regulation of DRP1 in midlife extends the lifespan and health of Drosophila by inducing mitochondrial fission and reducing the accumulation of dysfunctional mitochondria in aged flight muscle.

“Although positive regulation of DRP1 in midlife extends the lifespan and health of Drosophila by inducing mitochondrial fission and reducing the accumulation of dysfunctional mitochondria in aged flight muscle (Rana et al., 2017)”

• cites Rana et al., 2017 sourceSupported

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

Mitochondrial fragmentation is a significant factor in neurodegenerative diseases.

“Mitochondrial fragmentation, a process characterized by the division of mitochondria into smaller, dysfunctional organelles, has emerged as a significant factor in neurodegenerative diseases (Knott et al., 2008).”

• cites Knott et al., 2008 sourcePartly supported

  The Abstract and Introduction link disrupted mitochondrial dynamics to neurodegeneration, supporting the claim that fragmentation is a significant factor. However, the Mitochondrial Dynamics and Bioenergetics section reports that some cells have fragmented mitochondria without bioenergetic defects, so the sentence overstates the claim that the resulting organelles are necessarily dysfunctional. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

These changes contribute to mitochondrial dysfunction, synaptic loss, and neuronal degeneration, all of which are hallmark features of age-related neurodegenerative diseases such as Alzheimer's and Parkinson's disease.

“These changes contribute to mitochondrial dysfunction, synaptic loss, and neuronal degeneration, all of which are hallmark features of age-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease (Joshi et al., 2019; Bantle et al., 2020).”

• cites Joshi et al., 2019 sourcePartly supported

  The Abstract links mitochondrial dysfunction and fragmentation to neurodegenerative diseases including Alzheimer’s and Parkinson’s, and the Discussion links glial inflammatory responses to neuronal degeneration (page numbers unavailable). The passages do not establish synaptic loss as part of this sequence or characterize all three changes as hallmark features of age-related disease. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites Bantle et al., 2020 sourcePartly supported

  The Introduction identifies dopaminergic neuronal degeneration as a pathological hallmark of Parkinson’s disease and implicates mitochondrial dysfunction in its pathogenesis. It does not identify synaptic loss as a hallmark or establish the same set of features for Alzheimer’s disease, which it mentions only for comparison. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

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

In Drosophila ovarian germline stem cells as they age, mitochondrial fragmentation and DRP1 expression are both increased, while mitochondrial membrane potential is reduced.

“Consistent with our findings, in Drosophila ovarian germline stem cells as they age, mitochondrial fragmentation and the expression of the mitochondrial fission regulator, DRP1, are both increased, while mitochondrial membrane potential is reduced.”

• cites Amartuvshin et al., 2020 sourceSupported

Classified as probably not a substantial claim.

The red/green fluorescence ratio of JC-1 indicates the balance between healthy and dysfunctional mitochondria.

“The red/green ratio indicates the balance between healthy and dysfunctional mitochondria (Sivandzade et al., 2019).”

• cites Sivandzade et al., 2019 sourceSupported

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

The increase in oxygen consumption rate in aged normal human fibroblasts is associated with a shift in mitochondrial dynamics toward fusion.

“The increase in oxygen consumption rate in aged normal human fibroblasts is associated with a shift in mitochondrial dynamics toward fusion.”

• cites Son et al., 2017 sourceSupported

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

Fragmented mitochondria are often associated with decreased ATP production and compromised membrane potential, ultimately contributing to cellular dysfunction and pathological conditions.

“Fragmented mitochondria are often associated with decreased ATP production and compromised membrane potential, ultimately contributing to cellular dysfunction and pathological conditions (Motori et al., 2013; Joshi et al., 2019; Batista et al., 2021).”

• cites Motori et al., 2013 sourceNot checked — no full text of the source
• cites Joshi et al., 2019 sourceSupported
• cites Batista et al., 2021 sourcePartly supported

  The Discussion (page unavailable) links disrupted mitochondrial dynamics to impaired function and reports that reducing fragmentation alleviated loss of mitochondrial membrane potential in an Alzheimer’s mouse model. It also describes mitochondria’s role in energy production, but does not specifically say that fragmentation is associated with decreased ATP production. The paper’s disease-model evidence does not establish the full claim across pathological conditions generally. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

Mitochondrial dynamics are altered during physiological aging, affecting cell homeostasis via coordinated changes in cell signaling.

“These results demonstrate that mitochondrial dynamics are altered during physiological aging, affecting cell homeostasis via coordinated changes in cell signaling (Amartuvshin et al., 2020).”

• cites Amartuvshin et al., 2020 sourcePartly supported

  The Abstract reports that mitochondrial dynamics shift during physiological aging of Drosophila ovarian germline stem cells and affect stem cell homeostasis. The claim broadens this to cell homeostasis generally and reduces the reported mechanisms—stemness signaling, niche contact, and cellular metabolism—to cell signaling alone. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

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

Dysfunctional mitochondrial dynamics, particularly excessive mitochondrial fission, have been associated with oxidative stress, mitochondrial DNA damage, and cellular senescence in various cell types.

“Dysfunctional mitochondrial dynamics, as observed here, particularly excessive mitochondrial fission, have been associated with oxidative stress, mitochondrial DNA damage, and cellular senescence in various cell types (Twig et al., 2008; Miwa et al., 2022).”

• cites Twig et al., 2008 sourcePartly supported

  In “Inhibition of fission reduces mitochondrial autophagy” (page not provided), the paper reports increased oxidized mitochondrial proteins when fission is inhibited, but not increased ROS. “Mitochondrial dynamics and insulin secretion” (page not provided) discusses senescence in cells where fission has been hampered. These passages do not support excessive fission as the associated change, and the copy does not report mitochondrial DNA damage. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites Miwa et al., 2022 sourcePartly supported

  The section on mitochondrial mass homeostasis associates perturbed mitochondrial dynamics with senescence, and the section on ROS links mitochondrial dysfunction to oxidative stress and DNA damage. But the paper does not identify excessive fission as the associated change; it describes reduced FIS1 and mitochondrial elongation instead. Its ROS passage discusses DNA damage generally, not specifically mitochondrial DNA damage caused by altered dynamics. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

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

Mitochondrial dysfunction plays a pivotal role in the aging process, affecting cellular function including energy metabolism and oxidative stress.

“Mitochondrial dysfunction plays a pivotal role in the aging process, affecting various aspects of cellular function, including energy metabolism and oxidative stress.”

• cites Stefanatos and Sanz, 2018 sourceSupported

May combine two claims.

In cultures of senescent astrocytes and in the brains of elderly animals, there is an increase in fragmented mitochondria that correlates with the upregulation of DRP1 expression.

“We observed that in cultures of senescent astrocytes and in the brains of elderly animals, there is an increase in fragmented mitochondria that correlates with the upregulation of DRP1 expression.”

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

The discrepancy between increased expression of mitofusin 1, 2, and OPA1 in senescent cortical astrocyte cultures and unchanged expression of these proteins in the brains of aged animals is intriguing.

“The discrepancy between the increased expression of mitofusin 1, 2, and OPA1 in senescent cortical astrocyte cultures and the unchanged expression of these proteins in the brains of aged animals is intriguing.”

The quote only partly states this claim.

In the cerebral cortex of aged mice, DRP1 gene expression is increased by 34% compared to young controls.

“Using qPCR, we observed a 34% increase in the expression of DRP1, while no changes were detected in the expression of key fusion (MFN1 and OPA1) or fission (MFF and Fis1) genes (Figures 5A–E).”

May combine two claims.

Senescent astrocytes exhibit an increase in the quantity and a reduction in the size of mitochondria.

“In this study, we found that senescent astrocytes exhibited an increase in the quantity and a reduction in the size of mitochondria, which was confirmed by our in vivo evidence demonstrating the presence of mitochondria with smaller area and perimeter in astrocytes of elderly mice.”

May combine two claims.

Aging increases DRP1 expression and phosphorylation in the murine cerebral cortex.

“Aging increases DRP1 expression and phosphorylation in the murine cerebral cortex.”

• Also stated in: § Conclusion · plain

  “we observed an impairment in mitochondrial biogenesis and an increase in DRP1 expression and phosphorylation in the aged cerebral cortex”

The quote only partly states this claim.

In the cerebral cortex of aged mice, Fis1 gene expression is unchanged compared to young controls.

“Using qPCR, we observed a 34% increase in the expression of DRP1, while no changes were detected in the expression of key fusion (MFN1 and OPA1) or fission (MFF and Fis1) genes (Figures 5A–E).”

The quote only partly states this claim.

In the cerebral cortex of aged mice, OPA1 gene expression is unchanged compared to young controls.

“Using qPCR, we observed a 34% increase in the expression of DRP1, while no changes were detected in the expression of key fusion (MFN1 and OPA1) or fission (MFF and Fis1) genes (Figures 5A–E).”

May combine two claims.

We observed an impairment in mitochondrial biogenesis and an increase in DRP1 expression and phosphorylation in the aged cerebral cortex, both of which contribute to the observed age-related mitochondrial fragmentation in astrocytes.

“Furthermore, we observed an impairment in mitochondrial biogenesis and an increase in DRP1 expression and phosphorylation in the aged cerebral cortex, both of which contribute to the observed age-related mitochondrial fragmentation in astrocytes.”

• AssumptionRests on an assumption: Phosphorylation of DRP1 at Serine 616 indicates DRP1 activation.

The quote only partly states this claim.

In the cerebral cortex of aged mice, MFN1 gene expression is unchanged compared to young controls.

“Using qPCR, we observed a 34% increase in the expression of DRP1, while no changes were detected in the expression of key fusion (MFN1 and OPA1) or fission (MFF and Fis1) genes (Figures 5A–E).”

The quote only partly states this claim.

In the cerebral cortex of aged mice, MFF gene expression is unchanged compared to young controls.

“Using qPCR, we observed a 34% increase in the expression of DRP1, while no changes were detected in the expression of key fusion (MFN1 and OPA1) or fission (MFF and Fis1) genes (Figures 5A–E).”

May combine two claims.

Senescent astrocytes exhibit an accumulation of damaged mitochondria due to impaired mitophagy, resulting in increased susceptibility to cell death following a mitochondrial insult.

“Recently, we demonstrated that senescent astrocytes exhibit an accumulation of damaged mitochondria due to impaired mitophagy, resulting in increased susceptibility of astrocytes to cell death following a mitochondrial insult (Diniz et al., 2024a).”

• cites Diniz et al., 2024aNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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

Aging is associated with a decline in metabolic activity in the brain, including alterations in glucose metabolism and mitochondrial function.

“As individuals age, there is a decline in metabolic activity within the brain, including alterations in glucose metabolism and mitochondrial function (Peters, 2006).”

• cites Peters, 2006 sourceNot checked — no full text of the source

May combine two claims.

Senescent astrocytes exhibit an imbalance in regulatory proteins governing mitochondrial dynamics, with a tilt toward fission despite upregulation of fusion proteins.

“These findings suggest a potential imbalance in the regulatory proteins governing mitochondrial dynamics within senescent astrocytes, with a tilt toward fission despite the upregulation of fusion proteins.”

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

Animal handling and experimental procedures were approved by the Animal Use Ethics Committee of the Federal University of Rio de Janeiro (CEUA-UFRJ, approval protocol 119/23).

“Animal handling and experimental procedures were previously approved by the Animal Use Ethics Committee of the Federal University of Rio de Janeiro (CEUA-UFRJ, approval protocol 119/23).”

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

A decline in mitochondrial density in the aged brain has been previously reported.

“While a decline in mitochondrial density in the aged brain has been previously reported, our findings provide the first evidence of a reduction in mitochondrial biogenesis, which may underlie this phenomenon (Navarro and Boveris, 2010).”

• cites Navarro and Boveris, 2010Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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

A previous study from our group observed a decrease in TOMM20 levels and mitochondrial respiration in the cerebral cortex of aged animals.

“This finding is supported by a previous study from our group, which observed a decrease in TOMM20 levels and mitochondrial respiration in the cerebral cortex of aged animals (Diniz et al., 2024a).”

• cites Diniz et al., 2024aNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Senescent astrocytes exhibit fragmented mitochondria with compromised membrane potential, reflecting an imbalance in the mitochondrial fusion and fission pathways.

“Senescent astrocytes exhibit fragmented mitochondria with compromised membrane potential, reflecting an imbalance in the mitochondrial fusion and fission pathways.”