Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact

May combine two claims.

Proteostasis failure occurs in C. elegans in response to spaceflight, although it was not clear if this response was due only to muscle wasting.

“Proteostasis failure occurs in C. elegans in response to spaceflight, although it was not clear if this response was due only to muscle wasting (Honda et al., 2012).”

• cites Honda et al., 2012 sourceDisputed

  The Results (page not provided) report that space-flown C. elegans had fewer Q35 protein aggregates than ground controls—the opposite of the claimed proteostasis failure. The Discussion suggests that altered neuronal signaling may affect protein stability in muscle; it does not conclude that spaceflight caused proteostasis failure or attribute such a failure to muscle wasting. (LLM, conf=0.88)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

May combine two claims.

Astronauts had a decrease in 1,25 vitamin D levels, consistent with other studies.

“Astronauts had a decrease in 1,25 vitamin D levels (the active form of vitamin D) (Fig. 5B) consistent with other studies (Smith et al., 2005)”

• cites Smith et al., 2005 sourceDisputed

  The Bone markers section says that 1,25-dihydroxycholecalciferol, the active form of vitamin D, was not different after landing. It was 25-hydroxycholecalciferol—a different measure—that decreased; the paper describes similar findings in earlier studies for that measure. (LLM, conf=0.93)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

May combine two claims.

Exposure to space radiation and microgravity are primary hazards to astronauts' health in long-duration space missions.

“Exposure to space radiation and microgravity are primary hazards to astronauts’ health in long-duration space missions (Garrett-Bakelman et al., 2019).”

• cites Garrett-Bakelman et al., 2019 sourceSupported
  Experimental — accuracy not yet measured

May combine two claims.

Astronauts returning from ISS missions presented with health issues similar to geriatric stress, including bone and muscle mass loss, central nervous system issues, immune dysfunction, and cardiovascular health risks.

“astronauts that returned from missions on the International Space Station (ISS) presented with health issues similar to geriatric stress, including bone and muscle mass loss, central nervous system issues, immune dysfunction, and cardiovascular health risks (Strollo et al., 2018).”

• cites Strollo et al., 2018 sourcePartly supported

  The Introduction (page unavailable) says astronauts returning from long-term space missions have health problems resembling those of older people, particularly involving the immune system, bones, muscles, and cardiovascular system. The CNS Changes section also describes brain changes after long-term spaceflight. The paper does not establish that this full set of problems was observed specifically in astronauts returning from ISS missions; its statement is about long-term space missions generally. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

Phosphorylation of eIF2α reduces the cytosolic initiation complex, resulting in preferential translation of mRNAs with an upstream ORF and activates the integrated stress response.

“Phosphorylation of eIF2α reduces the cytosolic initiation complex (eIF2-GTP-Met-initiation tRNA), resulting in the preferential translation of mRNAs with an upstream ORF (uORF1) and activates the ISR (Balsa et al., 2019b; Quiros et al., 2017; Wong et al., 2019).”

• cites Balsa et al., 2019bNot matched

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

• cites Quiros et al., 2017 sourcePartly supported

  The Results section, “ATF4 is activated through the ISR” (page unavailable), says that eIF2α phosphorylation reduces total protein synthesis while allowing preferential translation of some transcripts with upstream ORFs, such as ATF4 and ATF5. It does not specify a reduction in the eIF2-GTP-Met-initiation-tRNA complex or identify uORF1, so those mechanistic details are not supported by our copy. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites Wong et al., 2019 sourcePartly supported

  The Introduction (page not provided) says eIF2α phosphorylation inhibits eIF2B, triggers the ISR, reduces translation initiation, and increases translation of certain mRNAs with special 5′-UTR sequences. It identifies the eIF2-GTP-Met-tRNAi complex but does not explicitly say its cytosolic abundance falls or specify an upstream ORF called uORF1. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

May combine two claims.

The liver regulates immune activity and lipid dysregulation during spaceflight.

“We focused on the liver since we previously demonstrated that the liver regulates immune activity and lipid dysregulation during spaceflight (Beheshti et al., 2019).”

• cites Beheshti et al., 2019 sourcePartly supported

  The Results ("Duration changes in livers from mice flown in space"; page unavailable) report increased adaptive-immune and fatty-acid pathways in mouse liver with longer spaceflight, alongside liver lipid accumulation. The paper does not demonstrate that the liver itself regulates immune activity or causes lipid dysregulation during spaceflight; it documents changes in liver tissue. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

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

Oxidative stress activates four kinases (GCN2, PKR, HRI, PERK) that initiate the integrated stress response by regulating phosphorylation of eIF2α.

“For example, oxidative stress activates four kinases (GCN2, PKR, HRI, PERK) that initiate the ISR by regulating the phosphorylation of the cytosolic translation elongation factor 2 alpha (eIF2α) (Pakos-Zebrucka et al., 2016).”

• cites Pakos-Zebrucka et al., 2016 sourcePartly supported

  The Activation section says all four eIF2α kinases become activated in response to oxidative stress, and the figure description says they converge on eIF2α phosphorylation at the core of the ISR. However, the citing sentence calls eIF2α a translation *elongation* factor; the Introduction identifies it as a translation *initiation* factor. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

May combine two claims.

The astronaut in the Twin Study passed only 2% of his lifespan in space, whereas mice from RR1 and RR3 missions passed approximately 25% of their lifespan at the ISS.

“The astronaut in the Twin Study passed only 2% of his lifespan in space (Garrett-Bakelman et al., 2019), whereas the mice from the RR1 and RR3 missions passed approximated 25% of their lifespan at the ISS.”

• cites Garrett-Bakelman et al., 2019 sourceSupported

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

IFN-γ, IL-1, and TNF pathways are linked to inflammation-induced muscle wasting.

“pathways linked to inflammation-induced muscle wasting (Londhe and Guttridge, 2015).”

• cites Londhe and Guttridge, 2015 sourcePartly supported

  The sections on IFN-γ and TNF-α link those cytokines to impaired muscle differentiation, damage, or loss of muscle mass. The IL-10 and IL-17 sections mention IL-1 as a pro-inflammatory cytokine, but do not link an IL-1 pathway specifically to muscle wasting. No page numbers were available in our copy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

The quote only partly states this claim.

The upregulation of NAD metabolism in the liver links oxidative stress and mitochondrial dysfunction.

“linking oxidative stress and mitochondrial dysfunction (Massudi et al., 2012).”

• cites Massudi et al., 2012 sourcePartly supported

  The “NAD+ in energy metabolism” section describes NAD+/NADH roles in mitochondrial respiration, and “Oxidative damage targets and types” connects NAD+ concentrations with redox potential. The paper does not establish that NAD metabolism is upregulated in the liver or that such upregulation links oxidative stress to mitochondrial dysfunction; its liver discussion concerns the size of the mitochondrial NAD+ pool. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

May combine two claims.

Urinary prostaglandin F2 alpha is increased in spaceflight and is associated with oxidative stress and cyclooxygenase-independent synthesis.

“Increased prostaglandin F2 alpha levels in urine are associated with oxidative stress and cyclooxygenase independent synthesis (Yin et al., 2007).”

• cites Yin et al., 2007 sourceSupported

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

A meta-analysis found increased risks of NAFLD and liver fibrosis in subjects with sarcopenia.

“A recent comprehensive meta-analysis across similar studies found increased risks of NAFLD and liver fibrosis in subjects with sarcopenia (Cai et al., 2020).”

• cites Cai et al., 2020 sourceSupported

May combine two claims.

An increase in ROS, as encountered in spaceflight, triggers adult stem cell differentiation and rapidly switches to mitochondrial OXPHOS.

“An increase in ROS, as encountered in spaceflight, triggers adult stem cells differentiation, and rapidly switches to mitochondrial OXPHOS (Hamanaka et al., 2013; Ito and Suda, 2014).”

• cites Hamanaka et al., 2013 sourcePartly supported

  The Introduction reports that mitochondrial ROS are required for differentiation of human bone marrow–derived mesenchymal stem cells into adipocytes, and the Results show that ROS support keratinocyte differentiation. The paper does not establish that spaceflight-associated ROS trigger adult stem-cell differentiation or cause a rapid switch to mitochondrial OXPHOS. The indexed passages provide section labels but no page numbers. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites Ito and Suda, 2014 sourcePartly supported

  The sections “Glycolysis and HIF in other adult stem cells” and “Switch to oxidative metabolism” say that ROS induced under normoxia can move adult stem cells out of quiescence and may prime differentiation, while differentiating HSCs need a rapid switch to mitochondrial OXPHOS. They do not establish that increased ROS directly triggers that switch or differentiation, and they do not address spaceflight. The copy provides section labels but no page numbers. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

Spaceflight induces mitochondrial stress, supported by increased urinary 8-OHdG and prostaglandin F2 alpha and by the paper's own analysis.

“The existence of spaceflight-induced mitochondrial stress is further supported by metabolite studies reporting increased urinary 8-OHdG and prostaglandin F2 alpha.”

• Also stated in: § Discussion · hedged

  “These markers are consistent with our analysis suggesting mitochondrial stress and dysfunction due to oxidative stress during spaceflight (Figs. 3B, 3F, and 3G).”

• cites Wu et al., 2004Not matched

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

• cites Yin et al., 2007 sourcePartly supported

  The Results section reports elevated urinary PGF2α in smokers and people with hypercholesterolemia and describes it as a potential marker of oxidative stress. The paper does not report spaceflight exposure, mitochondrial stress, or urinary 8-OHdG, so it cannot substantiate the sentence’s spaceflight-specific conclusion. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

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

Results from the analyses are consistent with previous studies and supported by multiple other omics studies.

“and the results from our analyses are consistent with those from previous studies (Beheshti et al., 2019; Suomalainen and Battersby, 2018) and are supported by multiple other omics studies (Bezdan et al., 2020; Gertz et al., 2020).”

• cites Beheshti et al., 2019 sourceSupported
• cites Suomalainen and Battersby, 2018 sourceNot checked — no full text of the source
• cites Bezdan et al., 2020 sourceSupported

Classified as probably not a substantial claim.

Increased oxidative stress and mitochondrial stress are implicated in causing androgenetic alopecia.

“Increased oxidative stress and mitochondrial stress were implicated in causing androgenetic alopecia (permanent hair loss) (Ho et al., 2019; Upton et al., 2015).”

• cites Ho et al., 2019Not matched

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

• cites Upton et al., 2015 sourcePartly supported

  The Abstract (page unavailable) says the in vitro findings suggest a role for oxidative stress in the pathogenesis of androgenetic alopecia. The paper does not identify mitochondrial stress as a contributor, and its evidence suggests a possible role rather than establishing that oxidative stress causes the condition. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Classified as probably not a substantial claim.

Microgravity induces muscle degeneration.

“Microgravity-induced muscle degeneration is well reported (Demontis et al., 2017; Nikawa et al., 2004).”

• cites Demontis et al., 2017 sourceSupported
  Experimental — accuracy not yet measured
• cites Nikawa et al., 2004 sourceNot checked — no full text of the source

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

Skeletal muscle depends on OXPHOS for energy production, and OXPHOS plays a role in regulating metabolism.

“Skeletal muscle also depends on OXPHOS for energy production (Kelley et al., 2002) reported to play a role in regulating metabolism (Argiles et al., 2016; Pratesi et al., 2013).”

• cites Kelley et al., 2002 sourceNot checked — no full text of the source
• cites Argiles et al., 2016 sourcePartly supported

  The Summary and Conclusions (page unavailable) identify skeletal muscle as a regulator of energy and protein metabolism. The Muscle Metabolism and Interorgan Crosstalk section describes aerobic metabolism in slow muscle fibers, but does not say that OXPHOS itself regulates metabolism. The claim that muscle depends on OXPHOS for energy production is attached to Kelley et al., not this source. (LLM, conf=0.82)

  Experimental — accuracy not yet measured
• cites Pratesi et al., 2013Not matched

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

May combine two claims.

Several conditions that lead to liver fibrosis are marked by specifically dysregulated metabolic pathways, including increases in metabolites involved in glycolysis/gluconeogenesis, fructose and mannose metabolism, tryptophan metabolism, valine, leucine, isoleucine metabolism, glycine, serine, and threonine metabolism, glutathione metabolism, glycerophospholipid metabolism, and tricarboxylic acid/

“Several conditions that lead to liver fibrosis are known to be marked by specifically dysregulated metabolic pathways, including significant increases in metabolites involved in glycolysis/gluconeogenesis, fructose and mannose metabolism, tryptophan metabolism, valine, leucine, isoleucine metabolism, glycine, serine, and threonine metabolism, glutathione metabolism, glycerophospholipid metabolism,”

• cites Chang and Yang, 2019 sourcePartly supported

  Section 4.2 (Animal Studies; page unavailable) reports alterations across the listed pathways in rat models of hepatic fibrosis, including CCl4-treated rats, but generally describes the metabolites as altered or perturbed, not significantly increased. Section 3.2 reports decreased branched-chain amino acids, including valine, leucine, and isoleucine, in some models, so the claim’s blanket assertion of increases is not supported. (LLM, conf=0.89)

  Experimental — accuracy not yet measured

May combine two claims.

PGC1α interacts with PPARγ, and PPARγ dysregulation in hair follicle stem cells produces results similar to scarring alopecia.

“PGC1α also interacts with PPARγ, and dysregulation of PPARγ has been shown in hair follicle stem cells (HFSCs) to produce similar results to scarring alopecia (i.e., hair loss disorder) (Karnik et al., 2009).”

• cites Karnik et al., 2009 sourcePartly supported

  The Introduction and Discussion (page numbers unavailable) report that deleting PPARγ in mouse hair follicle stem cells causes scarring alopecia resembling human disease. The cited paper’s passages do not establish the separate claim that PGC1α interacts with PPARγ. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Mitochondrial dysfunction attenuates platelet survival and increases risk for thrombovascular events, increasing stroke risk.

“mitochondrial dysfunction attenuates platelet survival and increased risk for thrombovascular events (Kunz et al., 2017; Melchinger et al., 2019), increasing stroke risk (Behrouzi and Punter, 2018).”

• cites Kunz et al., 2017 sourceCould not verify

  The Results report platelet concentrations during spaceflight, and the Discussion considers plasma-volume changes as a possible explanation. Neither passage addresses mitochondrial dysfunction, platelet survival, or thrombovascular events; searches for those terms found no supporting passage. The stroke-risk clause is separately cited to another source. (LLM, conf=0.76)

  Experimental — accuracy not yet measured
• cites Melchinger et al., 2019 sourcePartly supported

  The sections on platelet survival and disease link mitochondrial damage to premature platelet death and apoptotic platelets to faster clotting. The paper says preserving mitochondrial function may reduce thrombotic-event risk in diabetic patients, but does not establish the claim’s broader, unqualified increase in thrombovascular risk. The stroke-risk clause is cited to Behrouzi and Punter, not to this paper. (LLM, conf=0.83)

  Experimental — accuracy not yet measured
• cites Behrouzi and Punter, 2018 sourcePartly supported

  The Introduction identifies cerebral venous thrombosis (CVT) as a cause of stroke and says a cerebral venous thrombus can lead to infarction. That supports a link between CVT and stroke, but the paper does not establish that thrombovascular events generally increase stroke risk. The platelet-survival and mitochondrial-dysfunction claims are attributed to other citations, not this one. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

May combine two claims.

IFN-γ can induce a switch to aerobic glycolysis and has a significant role in proteasome regulation, linking mitochondrial dysfunction, innate immunity, and alterations in proteostasis.

“IFN-γ can induce a switch to aerobic glycolysis and has a significant role in proteasome regulation (Wang et al., 2018; Yang et al., 1992), linking mitochondrial dysfunction, innate immunity, and alterations in proteostasis.”

• cites Wang et al., 2018 sourcePartly supported

  The Introduction and Results report that IFN-γ increases aerobic glycolysis in macrophages, followed by reduced oxidative phosphorylation, and link that shift to mitochondrial ROS and inflammatory signaling (page numbers not supplied). The cited paper does not establish a role for IFN-γ in proteasome regulation or connect its findings to alterations in proteostasis. (LLM, conf=0.87)

  Experimental — accuracy not yet measured
• cites Yang et al., 1992 sourceNot checked — no full text of the source

May combine two claims.

Increased tryptophan, valine, leucine, isoleucine, TCA cycle, sphingolipid, and glycerophospholipid metabolites are reported in development and onset of fibrosis, with valine and bile acid synthesis related to more advanced stages.

“Increased tryptophan, valine, leucine, isoleucine, TCA cycle, sphingolipid, and glycerophospholipid metabolites are reported in the development and onset of fibrosis, with valine and bile acid synthesis related to more advanced stages (Chang and Yang, 2019; Musso et al., 2018).”

• cites Chang and Yang, 2019 sourcePartly supported

  Section 4.2 (Animal Studies) reports perturbations in the listed metabolites from the onset of hepatic fibrosis and dysregulation of valine and bile acid biosynthesis metabolites at intermediate and advanced stages. It does not say those metabolites increased; Section 3.2 reports decreased valine, leucine, and isoleucine in some fibrotic rat models. The claim also omits that the stage-specific finding came from CCl4-treated rats. (LLM, conf=0.89)

  Experimental — accuracy not yet measured
• cites Musso et al., 2018 sourceNot checked — no full text of the source

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

Vitamin D can modulate innate and adaptive immune responses because the vitamin D receptor is expressed on B cells, T cells, antigen-presenting cells, and dendritic cells.

“Vitamin D can modulate the innate and adaptive immune responses as the vitamin D receptor is expressed on B cells, T cells, antigen-presenting cells, and dendritic cells (Aranow, 2011).”

• cites Aranow, 2011 sourceSupported

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

Two mouse strains previously accumulated lipids in the liver due to spaceflight exposure.

“Two mouse strains were previously found to have accumulated lipids in the liver due to spaceflight exposure (Beheshti et al., 2019).”

• cites Beheshti et al., 2019 sourceSupported

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

Cardiovascular disease is linked to mitochondrial dysfunction through proteostasis failure related to lipid accumulation and ROS activity.

“Cardiovascular disease is also linked to mitochondrial dysfunction through proteostasis failure related to lipid accumulation and ROS activity (Alam et al., 2020; Arrieta et al., 2020).”

• cites Alam et al., 2020 sourcePartly supported

  The Introduction links impaired protein quality control and mitochondrial dysfunction to cardiac disease. The section “Electron Transport Chain and Oxidative Stress in Cardiac Proteostasis” links mitochondrial ROS, proteasome inhibition, and aggregate accumulation to cardiac proteotoxicity. It discusses accumulation of lipofuscin, not lipid accumulation generally, so that part of the claim is not supported. (LLM, conf=0.86)

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

  The 'Mitochondrial Proteostasis' section links disrupted mitochondrial protein quality control to impaired ATP production and cardiac function. 'Mitochondrial Proteostasis in Cardiac Pathology' reports increased reactive oxygen species after protease knockdown, but that finding was in myoblasts, not the heart. The passages do not link lipid accumulation to this proposed cardiovascular-disease pathway (page numbers unavailable). (LLM, conf=0.85)

  Experimental — accuracy not yet measured

May combine two claims.

Spaceflight is associated with dysregulation of adaptive immunity and an increased innate immunity profile.

“dysregulation of adaptive immunity occurring during spaceflight, consistent with an increased innate immunity profile on spaceflight (Crucian et al., 2018).”

• cites Crucian et al., 2018 sourceSupported

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

IFN-γ, IL-1, and TNF-α are known drivers of muscle wasting in chronic inflammatory diseases.

“IFN-γ, IL-1, and TNF-α are known to be drivers of muscle wasting in chronic inflammatory diseases (Londhe and Guttridge, 2015).”

• cites Londhe and Guttridge, 2015 sourceSupported

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

Proteostasis loss is a hallmark of aged muscles.

“proteostasis loss is a hallmark of aged muscles (Fernando et al., 2019).”

• cites Fernando et al., 2019 sourceSupported

May combine two claims.

Mitochondrial dysfunction inhibits cytosolic protein synthesis and defective protein quality control.

“Mitochondrial dysfunction inhibits cytosolic protein synthesis and defective protein quality control (Lu and Guo, 2020; Topf et al., 2019).”

• cites Lu and Guo, 2020 sourcePartly supported

  The section “Mitochondrial Outer Membrane-Associated Translation is Stalled by Mitochondrial Stress” (page unavailable) reports that persistent mitochondrial damage stalls translation of a specific mRNA at the mitochondrial outer membrane. The paper also links mitochondrial stress to altered protein quality control, but it does not establish that mitochondrial dysfunction broadly inhibits cytosolic protein synthesis or necessarily makes protein quality control defective. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites Topf et al., 2019 sourceNot checked — no full text of the source

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

Mitochondrial dysfunction is both a cause and a consequence of metabolic disorders.

“mitochondrial dysfunction is both a cause and a consequence of metabolic disorders (Bhatti et al., 2017).”

• cites Bhatti et al., 2017 sourceSupported

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

Vitamin D3 is modified through mitochondria in liver and kidney to assume its active form, 1,25 vitamin D.

“Vitamin D3 is modified through the mitochondria in the liver and kidney to assume its active form, 1,25 vitamin D (Bikle, 2014).”

• cites Bikle, 2014 sourcePartly supported

  The Summary and Conclusions and the 1α-hydroxylase section describe conversion of vitamin D to active 1,25(OH)2D, with the kidney the main source of its circulating form. The 25-hydroxylase section reports mitochondrial activity in the liver, but identifies the most important hepatic enzyme, CYP2R1, in the microsomal fraction. Thus the claim overstates that conversion proceeds through mitochondria in both organs. Page numbers were not supplied. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

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

Opposite trends in mitochondrial activity in liver and muscle are common in subjects with prediabetes or type 2 diabetes.

“opposite trends in mitochondrial activity in liver and muscle are common in subjects with prediabetes or diabetes type 2 (Bhansali et al., 2017; Pottecher et al., 2018).”

• cites Bhansali et al., 2017 sourceCould not verify

  The Materials and Methods (PBMCs Isolation; no page available) show that mitochondrial measures came from peripheral blood mononuclear cells, not liver and muscle. The Discussion describes differences between prediabetes and type 2 diabetes, but no passage establishes opposite trends in mitochondrial activity between liver and muscle in either group. (LLM, conf=0.75)

  Experimental — accuracy not yet measured
• cites Pottecher et al., 2018 sourcePartly supported

  The Introduction and Discussion describe impaired skeletal-muscle mitochondrial function in diabetes, including type 2 diabetes. The paper does not report liver mitochondrial activity or establish that opposite liver–muscle trends are common in people with prediabetes or type 2 diabetes. Its own experiments concern skeletal muscle in rats with a type 1 diabetes phenotype. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

Mitochondrial debris were observed in blood in the Twin Study, and mitochondrial DAMPs activate innate immune pathways.

“Mitochondrial debris were observed in blood in the Twin Study (Garrett-Bakelman et al., 2019) and mitochondrial damage-associated molecular patterns (DAMPs) activate innate immune pathways (Banoth and Cassel, 2018; Zhang et al., 2010).”

• cites Garrett-Bakelman et al., 2019 sourcePartly supported

  In Results, “Mitochondria-related adaptations during spaceflight” (page unavailable), the study reports mitochondrial DNA measured in blood plasma and increased mitochondrial RNA during flight. It does not identify the material in blood as mitochondrial debris. The DAMPs clause is attributed to other citations, not this paper. (LLM, conf=0.82)

  Experimental — accuracy not yet measured
• cites Banoth and Cassel, 2018 sourceSupported
• cites Zhang et al., 2010 sourceSupported

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

The first occurrence of venous thrombosis during spaceflight was reported in early 2020.

“Early in 2020, the first occurrence of venous thrombosis was reported during spaceflight (Aunon-Chancellor et al., 2020).”

• cites Aunon-Chancellor et al., 2020 sourcePartly supported

  The Abstract reports a confirmed venous thrombosis in an astronaut during an International Space Station mission, and the copy carries a 2020 copyright notice. It does not say this was the first occurrence during spaceflight or establish that it was reported early in 2020. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

May combine two claims.

Cell cycle and mitochondrial activity directly control circadian rhythm in cells and organisms.

“Cell cycle and mitochondrial activity directly control circadian rhythm in cells and organisms (Sardon Puig et al., 2018).”

• cites Sardon Puig et al., 2018 sourcePartly supported

  The Mitochondrial Dynamics section (page unavailable) reports that disrupting a mitochondrial-dynamics protein alters clock-gene oscillations in mouse cells, supporting a link between mitochondrial activity and circadian rhythms. The Conclusion (page unavailable) describes mitochondrial effects on the clock as possible mechanisms, not established direct control across cells and organisms. The cited passages do not support the separate claim about the cell cycle. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

The combination of replicating mtDNA and ROS would oxidize mtDNA, which would be released to activate the innate immune system inflammasome and Type I interferon pathway.

“The combination of replicating mtDNA and ROS would oxidize the mtDNA, which would be released to activate the innate immune system inflammasome and the Type I interferon pathway (West and Shadel, 2017; Zhong et al., 2018).”

• cites West and Shadel, 2017 sourceNot checked — no full text of the source
• cites Zhong et al., 2018 sourcePartly supported

  The Discussion (page unavailable) links newly synthesized mtDNA, oxidation, release of ox-mtDNA fragments, and NLRP3 inflammasome activation. The paper does not show that released ox-mtDNA activates the type I interferon pathway; its discussion of IRF1 concerns an upstream regulator of mtDNA synthesis and NLRP3 activation. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

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

G proteins regulate a wide range of cellular processes, including a significant role in synapse formation and elimination, affecting memory formation.

“They also regulate a wide range of cellular processes, including a significant role in synapse formation and elimination, affecting memory formation (Leung and Wong, 2017; Ye and Carew, 2010).”

• cites Leung and Wong, 2017 sourceSupported
• cites Ye and Carew, 2010 sourcePartly supported

  The Abstract says small G-proteins regulate a wide range of cellular processes, and the Regulation of Structural Plasticity section says Ras family proteins can regulate synapse structure, including processes involved in new synapse growth. That section mentions synapse elimination in connection with mental retardation, but does not establish that these proteins regulate elimination; it also describes the link between structural changes and memory storage as proposed. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

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

Immune dysregulation is strongly influenced by the cell cycle.

“Immune dysregulation is known to be strongly influenced by the cell cycle (Laphanuwat and Jirawatnotai, 2019).”

• cites Laphanuwat and Jirawatnotai, 2019 sourceSupported

May combine two claims.

Reduced NADH and radiation-induced DNA damage would reduce NAD+ levels, which would impair the circadian rhythm system through perturbed Sirt1 regulation of BMAL acetylation.

“The reduced NADH and radiation-induced DNA damage would reduce NAD+ levels (Fig. 3G), which would impair the circadian rhythm system through perturbed Sirt1 regulation of BMAL acetylation (Nakahata et al., 2008).”

• cites Nakahata et al., 2008 sourceSupported

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

GRK2 acts as a gatekeeper of mitochondrial function in the heart, and inhibition of GPR35 preserved mitochondrial function after myocardial infarction.

“G protein-coupled receptor kinase 2 (GRK2) was reported to act as a gatekeeper of mitochondrial function in the heart, and the inhibition of G protein-coupled receptor 35 (GPR35) preserved mitochondrial function after myocardial infarction (Chen et al., 2020; Sorriento et al., 2019).”

• cites Chen et al., 2020 sourceSupported
• cites Sorriento et al., 2019 sourceSupported

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

CoQ10 is an abundant lipid-soluble nutrient scavenging free radicals and protecting cells against oxidative damage.

“CoQ10 is an abundant lipid-soluble nutrient scavenging free radical and protecting cells against oxidative damage (Zhang et al., 2018).”

• cites Zhang et al., 2018 sourceSupported
  Experimental — accuracy not yet measured

May combine two claims.

Increases of acute inflammatory markers seen during exercise could be problematic to an already increased inflammatory pattern measured in astronauts, even though these markers are reduced by regular exercise in low-grade systemic inflammation patients.

“the increases of acute inflammatory markers seen during exercise (e.g., IL-6, TNF-a, IL1-RA, and IGF-1) could be problematic to an already increased inflammatory pattern we measured in astronauts (Fig. 5B), even though these markers are reduced by regular exercise in low-grade systemic inflammation patients (Contrepois et al., 2020; Khazaei, 2012).”

• cites Contrepois et al., 2020 sourcePartly supported

  Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured
• cites Khazaei, 2012Not checked — no full text of the source

May combine two claims.

Olfactory signaling has been directly linked to mitochondrial structure and glucose activity, indicating the paper uncovered a systemic impact on the body driven by mitochondria.

“Olfactory signaling has even been directly linked to mitochondrial structure and glucose activity (Kovach et al., 2016), indicating we have uncovered a systemic impact on the body driven by the mitochondria.”

• cites Kovach et al., 2016 sourceSupported

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

Sleep disorders are common in astronauts and in patients with primary mitochondrial diseases.

“Sleep disorders are common in astronauts (Wu et al., 2018) and patients with primary mitochondrial diseases (Ramezani and Stacpoole, 2014).”

• cites Wu et al., 2018Not matched

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

• cites Ramezani and Stacpoole, 2014 sourcePartly supported

  The Results report subjective sleep dysfunction in 15 of 20 patients evaluated at one neuromuscular center. But the Discussion says the prevalence of sleep pathology across patients with primary mitochondrial diseases is unknown and requires population-based studies, so the unqualified claim that it is common is not established. The astronaut clause is attributed to a different citation and is not assessed here. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

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

G proteins are ubiquitous inside cells and play an essential role in circadian regulation.

“G proteins are ubiquitous inside cells and play an essential role in circadian regulation (Doi et al., 2011).”

• cites Doi et al., 2011 sourcePartly supported

  The Discussion (page not provided) says that regulated intracellular G-protein signalling in the suprachiasmatic nucleus helps coordinate its neurons and contributes to the period of daily behavioural rhythms. This supports a role in circadian regulation, but the paper does not establish that G proteins are ubiquitous inside cells or that this role applies generally across cells. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

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

Mitochondrial Ca(2+) is a critical element in olfactory signaling, and in astronauts, smelling behavior changes occur potentially due to microgravity causing an upward shift of body fluid.

“mitochondrial Ca(2+) is a critical element in olfactory signaling (Fluegge et al., 2012) and in astronauts, smelling behavior changes occur potentially due to microgravity causing an upward shift of body fluid (Mukhopadhyay et al., 2016).”

• cites Fluegge et al., 2012 sourceNot checked — no full text of the source
• cites Mukhopadhyay et al., 2016 sourceSupported

May combine two claims.

ROS causes T cell cycle arrest, and T cell activation/proliferation requires a reducing extracellular microenvironment.

“ROS causes T cell cycle arrest (Belikov et al., 2015; Yan and Banerjee, 2010) and T cell activation/proliferation requires a reducing extracellular microenvironment (Yan and Banerjee, 2010).”

• cites Belikov et al., 2015 sourcePartly supported

  The Review section “T cells and oxidative stress” (page unavailable) reports that neutrophil-derived ROS inhibit DNA synthesis in human T cells and negatively affect their proliferation. It does not establish cell-cycle arrest specifically, and its finding concerns excessive, phagocyte-derived ROS rather than ROS in general. The reducing-extracellular-microenvironment clause is cited only to Yan and Banerjee, so it is not assessed against Belikov et al. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites Yan and Banerjee, 2010 sourcePartly supported

  The Abstract and Concluding Remarks state that T-cell activation and proliferation require a reducing extracellular microenvironment. The “Redox Signaling During T cell Activation” section says sustained pro-oxidant conditions inhibit proliferation, but does not establish that ROS causes T-cell cycle arrest; it also says low levels of ROS can promote activation. Page numbers are unavailable in our copy. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

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

CoQ10 is the strongest candidate and should be administered to the majority of primary mitochondrial diseases, independent of CoQ10 deficiency.

“The strongest candidate is the coenzyme Q10 (CoQ10) that should be administered to the majority of primary mitochondrial diseases (PMD), independent of CoQ10 deficiency (Camp et al., 2016).”

• cites Camp et al., 2016 sourceSupported

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

The field of nutritional mitochondrial therapeutics is still evolving, with some evidence pointing to effective treatments.

“The field of nutritional mitochondrial therapeutics is still evolving, with some evidence pointing to effective treatments (Camp et al., 2016; Rinninella et al., 2018).”

• cites Camp et al., 2016 sourceSupported
• cites Rinninella et al., 2018 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

A study on acute exercise in individuals with a spectrum of insulin resistance showed that acute physical activity triggers molecular responses on metabolic and energy-producing pathways, increasing glycolysis, TCA cycle, and fatty acid oxidation.

“A study on acute exercise in individuals with a spectrum of insulin resistance showed that acute physical activity triggers molecular responses on the metabolic and energy-producing pathways, increasing glycolysis, TCA cycle, and fatty acid oxidation (Contrepois et al., 2020).”

• cites Contrepois et al., 2020 sourceSupported

Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based). May combine two claims.

Cell cycle pathways were upregulated in all cell and tissue models except human T cells, where they were downregulated.

“Cell cycle pathways were upregulated in all cell and tissue models except in human T cells, where these same terms were downregulated (Fig. 7A and 7B).”

May combine two claims.

Observed changes include reduced antioxidant defenses and increased urinary markers of oxidative stress.

“reduced antioxidant defenses and increased urinary markers of oxidative stress (Fig. 3F)”

May combine two claims.

Pathway analyses across the multi-omic datasets showed significant enrichment for mitochondrial processes, innate immunity, chronic inflammation, cell cycle, circadian rhythm, and olfactory functions.

“Overall pathway analyses on the multi-omic datasets showed significant enrichment for mitochondrial processes, as well as innate immunity, chronic inflammation, cell cycle, circadian rhythm, and olfactory functions.”

May combine two claims.

Observed changes include altered mitochondria-associated metabolites and modified nDNA and mtDNA OXPHOS gene expression.

“Observed changes include altered mitochondria-associated metabolites and modified nDNA and mtDNA OXPHOS gene expression (Fig. 3B), reduced antioxidant defenses and increased urinary markers of oxidative stress (Fig. 3F), and altered integrated stress response (ISR) gene expression (Fig. 3C).”

May combine two claims.

Liver contained the most mitochondrial activity across all organs, while soleus and EDL had the most mitochondrial activity among muscles.

“Liver contained the most mitochondrial activity across all organs, while the soleus and EDL had the most mitochondrial activity amongst the muscles (Fig. 2E).”

May combine two claims.

Altered mitochondrial function and DNA damage were detected in urine and blood metabolic data from the astronaut cohort and NASA Twin Study.

“Evidence of altered mitochondrial function and DNA damage was also found in the urine and blood metabolic data compiled from the astronaut cohort and NASA Twin Study data, indicating mitochondrial stress as a consistent phenotype of spaceflight.”

May combine two claims.

Fgf21 was downregulated in liver or Gdf15 in soleus muscle.

“Finally, we observed the downregulation of the stress response genes Fgf21 or Gdf15 in liver or soleus muscle, respectively.”

May combine two claims.

In RR3, Gadd34 was down-regulated in oxidative soleus muscle and upregulated in glycolytic anterior tibialis muscle, while Atf5 was upregulated in anterior tibialis and EDL muscle.

“In the RR3 mission, Gadd34 was down-regulated in the oxidative soleus muscle and upregulated in the glycolytic anterior tibialis muscle, while the stress gene Atf5 was upregulated in both the anterior tibialis and in the EDL muscle, which is also a predominantly glycolytic muscle.”

May combine two claims.

IFN-γ and IFN-α gene sets were down-regulated in kidney and liver, with epigenetic analysis showing differential methylation of these same gene sets.

“Immune response through interferon-gamma (IFN-γ) and interferon-alpha (IFN-α) gene sets were down-regulated in the kidney and liver (Fig. 4B), with the epigenetic analysis showing differential methylation of these same gene sets (Fig. 5A).”

May combine two claims.

Spaceflight reduced astronauts' antioxidant capacity, coupled with an increase in urinary markers of oxidative stress including 8OHdG and Prostaglandin F2 alpha.

“While we observed an increase in mtDNA gene expression in the Twin Study, spaceflight reduced astronauts’ antioxidant capacity (Fig. 3F), coupled with an increase in urinary markers of oxidative stress including 8OHdG and Prostaglandin F2 alpha (PDGF2-alpha) (Table S4 and Fig. 3F).”

May combine two claims.

Lipid metabolism gene sets were upregulated in liver and kidneys and downregulated in eyes and adrenal gland.

“From our analysis of tissue pathways, lipid metabolism gene sets were upregulated in the liver and kidneys and downregulated in the eyes and adrenal gland (Fig. 6A).”

May combine two claims.

There were no robust changes in any of the genes from matched samples for the twin on Earth or in GAPDH.

“In contrast, there were no robust changes in any of the genes from matched samples for the twin on Earth or in GAPDH, a key cytosolic enzyme in the glycolytic pathway.”

May combine two claims.

In EDL, higher levels of mtDNA OXPHOS genes were observed, although nDNA-coded mitochondrial genes were not decreased.

“In the EDL, a highly glycolytic tissue, we observed higher levels of mtDNA OXPHOS genes (mt-Co1, mt-Co3, mt-Nd4, mt-Nd4l, mt-Nd5, mt-Atp6), although nDNA-coded mitochondrial genes were not decreased (Fig. 3B).”

May combine two claims.

Modeled flux through citrate synthase in flight versus ground control significantly decreased in muscle but was up in liver.

“Modeled flux through the citric acid cycle (CAC) gatekeeping enzyme Citrate Synthase (CSm, Fig. 6C–6D) in FLT vs GC significantly decreased in muscle but was up in liver.”

May combine two claims.

At the epigenetic level, only EDL and GST muscles showed altered methylation, with EDL showing alteration in IFN-α.

“At the epigenetic level, only EDL and GST muscles showed altered methylation, with EDL showing alteration in the IFN-α (Fig. 5A).”

May combine two claims.

CAC malate dehydrogenase flux is significantly reduced in flight versus ground control muscle, as are mitochondrial Carnitine O acetyltransferase and Malonyl-CoA Decarboxylase.

“The CAC malate dehydrogenase (MDHm) flux that converts malate to oxaloacetate is significantly reduced in FLT vs GC muscle, as are mitochondrial Carnitine O acetyltransferase (CSNATm), which converts carnitine into acetyl carnitine, and Malonyl-CoA Decarboxylase (MCD), which converts the fatty acid metabolism antagonist malonyl-CoA (Brady et al., 1993) (Fig. 6C–6D).”

• cites Brady et al., 1993 sourceNot checked — no full text of the source

May combine two claims.

Astronauts had higher levels of total cholesterol and LDL cholesterol, accompanied by decreased HDL cholesterol during spaceflight.

“We found higher levels of total cholesterol and low-density lipoprotein (LDL) cholesterol, accompanied by decreased levels of high-density lipoprotein (HDL) cholesterol.”

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

The third major grouping of GSEA pathway hits focused on lipid biology.

“The third major grouping of GSEA pathway hits focused on lipid biology.”

May combine two claims.

CD19 cells had the greatest increase in mitochondrial activity post-flight for the twin in space, while mitochondrial activity in the CD4 population was significantly reduced in-flight and post-flight.

“CD19 cells had the greatest increase in mitochondrial activity post-flight for the twin in space, while mitochondrial activity in the CD4 population was significantly reduced in-flight and post-flight (Fig. 3D).”

May combine two claims.

In cell line data, hair follicles show increased expression of genes related to mitochondrial activity, while other cells show reduced expression.

“Our analysis from the cell line data shows hair follicles exhibit increased expression of genes related to mitochondrial activity, while other cells show reduced expression (Fig. 2A).”

May combine two claims.

ECM related pathways were unaltered in quadriceps, upregulated in SLS, EDL, GST, and TA muscles, and downregulated in carotid artery.

“ECM related pathways were unaltered in the quadriceps, upregulated in SLS, EDL, GST, and TA muscles, and downregulated in the carotid artery (Fig. 7C).”

May combine two claims.

Muscle metabolic flux is reduced in FLT versus GC, while the liver shows the opposite result.

“The reduction of muscle metabolic flux when comparing between FLT vs GC vs the opposite result in liver (Figs. 3G, 6C, and 6D)”

May combine two claims.

The complement system and pathways related to IFN-γ and IFN-α change in internal organs.

“The complement system and pathways related to IFN-γ and IFN-α change in the internal organs (Fig. 4B).”

May combine two claims.

Spaceflight caused increased expression of cell cycle genes in fibroblasts, endothelial cells, and hair follicles, but down-regulated these genes in T cells.

“Spaceflight caused an increased expression of cell cycle genes in fibroblasts, endothelial cells, and the hair follicles, but these genes were down-regulated in T cells (Fig. 7A).”

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

Chronic low doses of radiation exposure increase cancer risk.

“In addition to the known increased cancer risk from chronic low doses of radiation exposure (Durante and Cucinotta, 2008), astronauts that returned from missions on the International Space Station (ISS) presented with health issues similar to geriatric stress, including bone and muscle mass loss, central nervous system issues, immune dysfunction, and cardiovascular health risks (Strollo et al., 2”

• cites Durante and Cucinotta, 2008 sourceNot checked — no full text of the source

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

The liver acts as a dynamic and critical hub in sensing changes in blood composition and maintaining homeostasis.

“Second, the liver undergoes more differential gene and protein expression changes than other organs, consistent with the role the liver plays as a dynamic and critical hub in sensing changes in blood composition and maintaining homeostasis.”

May combine two claims.

Mitochondrial dysfunction may alter metabolic flux through mitochondrial pathways, perturb mitochondrial gene expression, and activate the integrated stress response.

“These and related observations suggest that mitochondrial dysfunction may alter metabolic flux through mitochondrial pathways, perturb mitochondrial gene expression, and activate the ISR.”

May combine two claims.

Spaceflight suppresses nDNA-coded mitochondrial OXPHOS gene expression predominantly in oxidative tissues, and induction of mtDNA genes partially compensates for diminished mitochondrial oxidative metabolism.

“These observations support the conclusion that spaceflight suppresses nDNA-coded mitochondrial OXPHOS gene expression predominantly in oxidative tissues, and the induction of the mtDNA genes partially compensates for the diminished mitochondrial oxidative metabolism.”

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

Dietary intake before or after spaceflight was not assessed.

“We did not assess dietary intake before or after spaceflight.”

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

Urinary 8-OHdG is a biomarker of generalized cellular oxidative stress, a marker of oxidized DNA that signals DNA repair, and a risk factor for cancer, atherosclerosis, and diabetes.

“Urinary 8-OHdG is a biomarker of generalized cellular oxidative stress, a marker of oxidized DNA that signals that DNA repair is occurring, and a risk factor for cancer, atherosclerosis, and diabetes (Wu et al., 2004).”

• cites Wu et al., 2004Not matched

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

May combine two claims.

Spaceflight impacts lipid metabolism at the hepatic gene expression level, extending to the circulating lipid profile.

“These results indicate that spaceflight impacts lipid metabolism at the hepatic gene expression level, extending to the circulating lipid profile.”

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

Mice and humans have different biochemical reaction speeds that affect development.

“a particularly important consideration given the recent findings that mice and humans have different biochemical reaction speeds that affect development (Matsuda et al., 2020).”

• cites Matsuda et al., 2020 sourceNot checked — no full text of the source

May combine two claims.

From the murine perspective, the RR1 and RR3 missions were long-term space missions.

“From the murine perspective, this was a long-term space mission, a particularly important consideration given the recent findings that mice and humans have different biochemical reaction speeds that affect development (Matsuda et al., 2020).”

May combine two claims.

Atf5, Chop, and Gdf15 are downregulated in oxidative muscle during spaceflight, consistent with reduced integrated stress response.

“Therefore Atf5, Chop, and Gdf15 are downregulated in oxidative muscle during spaceflight, consistent with reduced ISR.”

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

Nikawa and collaborators proposed a spaceflight-specific, induced mitochondrial activity alteration associated with muscle atrophy in 2004.

“Nikawa and collaborators proposed a spaceflight-specific, induced mitochondrial activity alteration associated with muscle atrophy in 2004 (Nikawa et al., 2004).”

• cites Nikawa et al., 2004 sourceNot checked — no full text of the source

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

The reduction of muscle metabolic flux in FLT versus GC and the opposite liver result may be due to the liver's response to muscle wasting (sarcopenia).

“may be due to the liver’s response to muscle wasting (sarcopenia).”

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

Sarcopenia is an independent risk factor for liver fibrosis in NAFLD cohorts, independent of obesity, inflammation, and insulin resistance.

“Sarcopenia is an independent risk factor for liver fibrosis in non-alcoholic fatty liver disease (NAFLD) cohorts, independent of obesity, inflammation, and insulin resistance (Koo et al., 2017).”

• cites Koo et al., 2017 sourceNot checked — no full text of the source

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

Oxidative stress is critical to mitochondria-mediated disease processes.

“Oxidative stress is critical to mitochondria-mediated disease processes (Wallace, 2013).”

• cites Wallace, 2013 sourceNot checked — no full text of the source

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

Increases in renin impact circadian rhythm activity.

“and increases in renin impact circadian rhythm activity (Ohashi et al., 2017).”

• cites Ohashi et al., 2017 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Cell cycle dysfunction is heavily involved with all the other pathways discussed.

“Cell cycle dysfunction is heavily involved with all the other pathways discussed below.”

May combine two claims.

Urinary 8-OHdG is increased in spaceflight and is a biomarker of cellular oxidative stress related to DNA repair.

“increased urinary 8-OHdG and prostaglandin F2 alpha. 8-OHdG is a biomarker of cellular oxidative stress related to DNA repair (Wu et al., 2004).”

• cites Wu et al., 2004Not matched

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

May combine two claims.

Mouse ISS data, astronaut studies, and NASA Twin Study data all strongly support an alteration in electron transport chain reaction and ATP production in mitochondria.

“Specifically, mouse ISS data (Fig. 3B), astronaut studies (Fig. 3F), and the NASA Twin Study data (Fig. 3E) all strongly support an alteration in the electron transport chain reaction and ATP production in the mitochondria.”

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

Another study reported decreased mitochondrial activity in the roots of space-flown soybean seedlings.

“Another study reported decreased mitochondrial activity in the roots of space-flown soybean seedlings (Klimchuk, 2007).”

• cites Klimchuk, 2007 sourceNot checked — no full text of the source

May combine two claims.

Lower diffusion rates of solutes in microgravity reduce the hydrogen gradient at the mitochondrial intermembrane space, reducing electron transport chain and ATP synthesis.

“and the lower diffusion rates of solutes in microgravity (Smith et al., 2009) reduce the hydrogen gradient at the mitochondrial intermembrane space, reducing electron transport chain and ATP synthesis (Nelson, 2013).”

• cites Smith et al., 2009 sourceNot checked — no full text of the source
• cites Nelson, 2013Not 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).

Muscle loss may relate to increased metabolic flux changes in spaceflight for mouse liver versus muscle.

“We suggest that muscle loss may relate to the increased metabolic flux changes in spaceflight for the mouse liver versus muscle”

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

Adequate energy, protein, and vitamin D supply are essential for bone mineral density maintenance after six months of spaceflight.

“Adequate energy, protein, and vitamin D supply are essential for bone mineral density maintenance after six months of spaceflight (Smith et al., 2012b).”

• cites Smith et al., 2012bNot 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.

Inflammation leads to changes in lipid metabolism, and persistence of inflammatory stimulus can lead to chronic lipid changes associated with metabolic syndrome.

“inflammation leads to changes in lipid metabolism, and the persistence of the inflammatory stimulus can lead to chronic lipid changes associated with metabolic syndrome (Esteve et al., 2005).”

• cites Esteve et al., 2005 sourceNot checked — no full text of the source

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

Vitamin D3 supplementation prevents 1,25 vitamin D loss, leading NASA to increase vitamin D supplementation to 1000 IU/d.

“Vitamin D3 (cholecalciferol) supplementation prevents 1,25 vitamin D loss, leading NASA to increase the vitamin D supplementation to 1000 IU/d (Douglas, 2020).”

• cites Douglas, 2020Not 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.

Cardiovascular risk is related to lipid disorders, and associations between dysregulation of mitochondrial energy metabolism and poor cardiac health are common.

“cardiovascular risk is related to lipid disorders (Stein et al., 2019) and associations between dysregulation of mitochondrial energy metabolism and poor cardiac health are common (Meyers et al., 2013).”

• cites Stein et al., 2019 sourceNot checked — no full text of the source
• cites Meyers et al., 2013Not checked — no full text of the source

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

The liver is the body's central metabolic organ and where LDL is produced.

“the liver being the body’s central metabolic organ and where LDL is produced (Nelson, 2013).”

• cites Nelson, 2013Not 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).

Lipid metabolism changes can be caused by inflammation.

“Lipid metabolism changes can also be caused by inflammation (Esteve et al., 2005)”

• cites Esteve et al., 2005 sourceNot checked — no full text of the source

May combine two claims.

Because no lipid pathway changes were observed in cell line data, lipid metabolism changes are suggested to derive from complex interactions at tissue and organ levels.

“since no lipid pathway changes were observed in cell line data, we suggest lipid metabolism changes are derived from complex interactions at the tissue and organ levels.”

May combine two claims.

The lipid/glycolytic metabolic flux imbalance in liver of mice flown to space is related to onset of fibrosis and directly involves mitochondrial oxidative phosphorylation modulation.

“The lipid/glycolytic metabolic flux imbalance occurring in liver for mice flown to space-related to the onset of fibrosis is directly involved with the mitochondrial process, which involves modulation of oxidative phosphorylation (Diamond et al., 2007) (Fig. 3B).”

• cites Diamond et al., 2007 sourceNot checked — no full text of the source

May combine two claims.

This would activate ATF4 transcription factor to upregulate expression of FGF21 and GDF15 and induce mitochondrial supercomplex assembly factor SCAF1.

“This would activate the ATF4 transcription factor to upregulate expression of FGF21 and GDF15 and induce the mitochondrial supercomplex assembly factor SCAF1 (Balsa et al., 2019a; Khan et al., 2017a).”

• cites Balsa et al., 2019aNot matched

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

• cites Khan et al., 2017aNot matched

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

May combine two claims.

Exercise counteracts the effect of microgravity on the cardiovascular system; nonetheless, neither exercise intensity nor duration was sufficient to prevent vascular changes such as increased arterial and intima-media thickness, cardiac atrophy, and development of insulin resistance.

“Exercise also counteracts the effect of microgravity on the cardiovascular system; nonetheless, neither exercise intensity nor duration showed sufficient to prevent vascular changes as increased arterial and intima-media thickness, cardiac atrophy, and the development of insulin resistance (Hughson et al., 2018).”

• cites Hughson et al., 2018 sourceNot checked — no full text of the source

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

All subjects provided written informed consent.

“all subjects provided written informed consent”

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

The study protocols were reviewed and approved by the NASA Institutional Review Board.

“All protocols were reviewed and approved by the NASA Institutional Review Board”

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

The R+0 samples were not necessarily fasting, given the time of day and nature of return from flight.

“The R+0 samples were not necessarily fasting, given the time of day and nature of return from flight.”

May combine two claims.

The mice in space and ground control were maintained in a 12/12 light/dark cycle and were not subjected to workload activities that commonly impact astronauts, which rules out both possible causes for the circadian alteration.

“In this study, the mice in space and ground control were maintained in a 12/12 light/dark cycle. They were not subjected to any workload activities that commonly impact astronauts, which rules out both possible causes for this alteration.”

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

This concept can guide new nutritional and pharmaceutical interventions and studies that will increase the viability of long-term human-crewed space missions.

“This concept can guide new nutritional and pharmaceutical interventions and studies that will increase the viability of long-term human-crewed space missions.”

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

All available data are reported, although the reported n for any given test or session varies due to several reasons.

“All available data are reported here, although the reported n for any given test or session varies for a number of reasons”

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

All samples in the metabolomic profiling were randomized.

“All samples were randomized.”

Classified as probably not a substantial claim.

The Van der Waerden p-values were not adjusted for multiple testing correction because of the likelihood of over-penalization of strongly dependent fluxes in and between pathways.

“Resulting VdW p-values were not adjusted for multiple testing correction because of the likelihood of over-penalization of strongly dependent fluxes in and between pathways.”

May combine two claims.

The principal countermeasure applied to astronauts is exercise; astronauts onboard the ISS exercise for up to 2 hours per day, but there is still a considerable decrease in muscle mass and bone loss observed after landing.

“The principal countermeasure applied to astronauts is exercise; astronauts onboard the ISS exercise for up to 2 hours per day, but there is still a considerable decrease in muscle mass, and bone loss observed after landing (Clément, 2011).”

• cites Clément, 2011 sourceNot checked — no full text of the source

May combine two claims.

Alteration in mitochondrial protein production would activate the mitochondrial unfolded protein response, which would trigger the integrated stress response pathway, causing phosphorylation of cytosolic initiation factor eIF2α.

“Alteration in mitochondrial protein production would activate the mitochondrial unfolded protein response (Fig. 7A), which would trigger the integrated stress response pathway (Fig. 3C), causing phosphorylation of the cytosolic initiation factor eIF2α.”

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

G proteins are heavily involved with the renin-angiotensin system, with activation of G proteins resulting in similar increases to the renin levels observed.

“G proteins are heavily involved with the renin-angiotensin system, with the activation of G proteins resulting in similar increases to the renin levels we observed (Fig. 7E). (Balakumar and Jagadeesh, 2014).”

• cites Balakumar and Jagadeesh, 2014 sourceNot checked — no full text of the source

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

Based on post-flight analysis of RR-2 Habitat telemetry data, ISSESs were programmed to be two degrees Celsius higher than ISS cabin data; the result was that internal temperatures of ground control habitats matched flight Habitats closely for most of the experiment.

“Based on post-flight analysis of the RR-2 Habitat telemetry data, the ISSESs were programmed to be two degrees Celsius higher than the ISS cabin data; the result of this off-set was that the internal temperatures of the ground control habitats matched the flight Habitats closely for most of the experiment.”

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

Multiple comparisons were accounted for, and only tests with p<0.001 are reported.

“Multiple comparisons were accounted for, and only those tests with p<0.001 are reported.”

May combine two claims.

These factors increase in the liver, indicating exercise may not be enough to counteract the stressors in space.

“At the same time, these factors increase in the liver (Fig. 6C), indicating exercise may not be enough to counteract the stressors in space.”

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

CoQ10 is currently being tested on the ISS as a countermeasure for retinal lesions, and data from this project could help elucidate if CoQ10 could be used as a more general intervention.

“CoQ10 is currently being tested on the ISS as a countermeasure for retinal lesions, and data from this project could help elucidate if CoQ10 could be used as a more general intervention (Lulli et al., 2019).”

• cites Lulli et al., 2019Not 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.

All animal procedures were approved by IACUC at NASA ARC and KSC and carried out in accordance with relevant guidelines and regulations.

“All animal procedures performed in these experiments were approved by the Institutional Animal Care and Use Committees (IACUC) for flight at the NASA Ames Research Center (ARC) and the Kennedy Space Center (KSC) and the methods were carried out in accordance with relevant guidelines and regulations.”

May combine two claims.

Reduced mitochondrial function with sustained calories would generate excess mitochondrial ROS and activate compensatory mtDNA replication, resulting in increased mtDNA transcripts.

“Reduced mitochondrial function with sustained calories would generate excess mitochondrial ROS and activate compensatory mtDNA replication, resulting in increased mtDNA transcripts.”