A spatio-temporal brain miRNA expression atlas identifies sex-independent age-related microglial driven miR-155-5p increase

May combine two claims.

CD11b+/CD45+ brain cells are mainly infiltrating macrophages, so we exclude these macrophages with our sorting strategy.

“As CD11b+/CD45+ brain cells are mainly infiltrating macrophages53, we exclude these macrophages with our sorting strategy.”

• cites [53] Rayaprolu, S. et al. Flow-cytometric microglial sorting coupled with quantitative proteomics identifies moesin as a highly-abundant microglial protein with relevance to Alzheimer's disease. Mol Neurodegener. 15, 28 (2020). sourceDisputed

  The Methods section (Acute isolation of CD11b-positive microglia; page unavailable) says CD11b+ brain myeloid cells are predominantly microglia, while CD45high brain-infiltrating macrophages make up less than 5% of them. It also says the authors sorted CD11b+ cells rather than using a CD11b+CD45int selection strategy. This contradicts the cited premise that these cells are mainly infiltrating macrophages. (LLM, conf=0.90)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

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

MiR-9-5p is known to be involved in neurogenesis, axon development, differentiation, and proliferation of neural progenitor cells.

“MiR-9-5p is known to be involved in neurogenesis, axon development, differentiation, and proliferation of neural progenitor cells27.”

• cites [27] Sim, S. E. et al. The brain-enriched MicroRNA miR-9-3p regulates synaptic plasticity and memory. J. Neurosci. 36, 8641–8652 (2016). sourceSupported

May combine two claims.

For miRNAs, sex was responsible for 0.2% of variation and 2.8% in combination with brain region.

“The variable sex was responsible for 0.2% of the variation and for 2.8% in combination with the brain region (Fig. 1g).”

May combine two claims.

GSEA over miRNAs in motor cortex, caudate putamen, and thalamus revealed overlaps between regulated pathways; 'cerebral cortex radially oriented cell migration' was depleted in all three regions and 'complement-dependent cytoxicity' was enriched.

“A gene set enrichment analysis (GSEA) over the miRNAs in mot. cortex, caudate putamen, and thalamus revealed overlaps between regulated pathways (Fig. 2e). E.g., “cerebral cortex radially oriented cell migration” was depleted in all three regions and “complement-dependent cytoxicity” was enriched.”

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

Cluster 52 contained only one trajectory and was excluded from further evaluations.

“Note, cluster 52 contained only one trajectory; hence, we excluded it from further evaluations.”

May combine two claims.

Correlating each feature with age per brain region revealed 720 positive correlated tRNAs and 127 negatively correlated miRNAs (51 positively correlated miRNAs).

“Correlating each feature with age per brain region revealed 720 positive correlated tRNAs and 127 negatively correlated miRNAs (51 positively correlated miRNAs, Fig. 1b).”

May combine two claims.

In motor cortex, 26 miRNAs were significantly upregulated and one miRNA significantly downregulated between male and female.

“In the motor cortex, 26 miRNAs were significantly upregulated and one miRNA significantly downregulated.”

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

For the aDR study, 1345 features were obtained after filtering.

“For both, we mapped 1966 features and obtained 1345 and 1382 features after filtering, respectively.”

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

miR-5100 was not detected in microglia.

“Unfortunately, miR-5100 was not detected.”

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

For the YMP study, 1382 features were obtained after filtering.

“For both, we mapped 1966 features and obtained 1345 and 1382 features after filtering, respectively.”

May combine two claims.

In our aging brain region-specific miRNA atlas, we identified region-specific miRNA signatures, especially in the olfactory bulb and cerebellum in males and medulla and pons in females.

“In our aging brain region-specific miRNA atlas, we identified region-specific miRNA signatures, especially in the olfactory bulb and cerebellum in males and medulla and pons in females.”

May combine two claims.

For YMP, no significant miR-155-5p expression changes compared to control groups were detected, but decreased expression was observed in corpus callosum, cerebellum, caudate putamen, medulla, and choroid plexus and an increase in mot. cortex.

“Similarly, for YMP, we did not detect any significant miR-155-5p expression changes compared to control groups, however we observed decreased expression in corpus callosum, cerebellum, caudate putamen, medulla, and choroid plexus and an increase in mot. cortex (Supplementary Fig. 9k).”

May combine two claims.

miR-155-5p and miR-146a-5p were significantly correlated with age in males and females.

“Apart from miR-5100, miR-155-5p and miR-146a-5p were significantly correlated with age in males and females”

May combine two claims.

Two clusters (24 and 38) exhibited a continuous decrease in expression. Neither of these clusters were region-specific.

“Two clusters (24 and 38) exhibited a continuous decrease in expression. Neither of these clusters were region-specific.”

May combine two claims.

An aggregation of significant results showed a high number of significantly upregulated miRNAs in choroid plexus (214 miRNAs) and significant downregulation in pons (94 miRNAs), SVZ (82 miRNAs) and choroid plexus (54 miRNAs).

“An aggregation of the significant results resolved showed a high number of significantly upregulated miRNAs in choroid plexus (214 miRNAs) and significant downregulation in pons (94 miRNAs), SVZ (82 miRNAs) and choroid plexus (54 miRNAs) (Supplementary Fig. 4f).”

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

In the olfactory bulb, median expression of miR-9-5p was over 100k rpmm.

“In the olfactory bulb, we detected a median expression of over 100k rpmm.”

May combine two claims.

MiR-10b-3p and miR-10b-5p were signature miRNAs in the medulla and shared between medulla and pons were miR-1a-1-5p and miR-10a-3p/5p.

“MiR-10b-3p and miR-10b-5p were the signature miRNAs in the medulla and shared between medulla and pons were miR-1a-1-5p and miR-10a-3p/5p.”

May combine two claims.

In combined analysis, fewer miRNAs were significantly positively correlated with age and more were significantly anti-correlated, especially driven by 75 anticorrelated miRNAs in pons.

“We found less miRNAs significantly positively correlated with age in the combined analysis and more miRNAs significantly anti-correlated, especially driven by 75 anticorrelated miRNAs in pons.”

May combine two claims.

59 miRNAs were upregulated in aged microglia and 70 miRNAs downregulated.

“A detailed analysis of deregulated miRNA between these two groups revealed 59 miRNAs upregulated in aged microglia and 70 miRNAs downregulated (cf. Methods, Fig. 5f, Supplementary Data 11).”

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

The microglia dataset consisted of 8 samples, all of which survived filtering, and 419 features survived filtering using an adjusted threshold of 1.8 million reads.

“The microglia dataset consisted of 8 samples, of which all samples and 419 features survived the filtering using an adjusted threshold of 1.8 million reads.”

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

For the YMP study, 68 out of 84 samples were kept after filtering.

“and 68 out of 84 samples for the YMP study.”

May combine two claims.

In females, 63 miRNAs were significantly positively correlated in choroid plexus and 13 were significantly anti-correlated in the SVZ.

“In females, 63 miRNAs were significantly positively correlated in choroid plexus and 13 were significantly anti-correlated in the SVZ.”

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

Human ROSMAP data after filtering yielded 203 samples and 280 miRNAs.

“So, after filtering, we obtained 203 samples and 280 miRNAs.”

May combine two claims.

The average number of significantly age-correlated miRNAs in a +/−10kb window is 5.27 on the same strand and 0.25 on the opposite strand.

“As a reference, the average number in this defined neighborhood is 5.27 on the same strand and 0.25 miRNAs on the opposite strand.”

May combine two claims.

In females, region-specific miRNAs and significant age-related miRNAs were detected, but no simultaneously region-specific and age-related miRNAs were detected.

“In females, we detected region-specific miRNAs as well as significant age-related ones, but again, no simultaneously region-specific and age-related miRNAs were detected.”

Classified as probably not a substantial claim.

For 66 of the 82 target genes, expression values from 809 samples matching to the miRNA samples were obtained using gene data from Hahn et al.

“Using the gene data from Hahn et al.3, we obtained for 66 of the target genes expression values from 809 samples matching to the miRNA samples.”

• cites Hahn et al. [3] Hahn, O. et al. Atlas of the aging mouse brain reveals white matter as vulnerable foci. Cell 186, 4117–4133 e4122 (2023). sourceNot checked yet

  Queued — the background check reaches it, usually within a day.

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

Analyzing the composition of expressed counts per brain region indicated a homogenous distribution.

“Analyzing the composition of expressed counts per brain region indicated a homogenous distribution (Supplementary Fig. 1f).”

May combine two claims.

In females, pons and medulla exhibited strong regional expression signatures, each forming a separate cluster.

“In females, pons and medulla exhibited strong regional expression signatures, by each forming a separate cluster.”

May combine two claims.

Between oldest (92-102 years) and youngest (71-80 years) human ROSMAP groups, 144 downregulated and 10 upregulated miRNAs were found in females and 42 downregulated and 32 upregulated miRNAs in males.

“Between the oldest (92–102 years) and the youngest (71–80 years) group, we found 144 downregulated and 10 upregulated miRNAs in females and 42 downregulated and 32 upregulated miRNAs in males (Fig. 3g, cf. Methods).”

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

For the aging cohort, after filtering, 828 samples and 1174 miRNAs were kept.

“from which we kept 828 samples and 1174 miRNAs (3424 lncRNAs, 605 piRNAs, 194 rRNAs, 27 scaRNAs, 672 snoRNAs, 705 snRNAs and 404 tRNAs).”

May combine two claims.

For five regions, the share of variation explainable by age (>12%) dominated over the share explainable by sex (<10%) and the combination between age and sex (<3%).

“However, our study focusses on age-related miRNA expression patterns and for five regions the share of variation explainable by age (>12%) dominated over the share explainable by sex (<10%) and the combination between age and sex (<3%) (Fig. 2c).”

May combine two claims.

Cerebellum and choroid plexus stood out with 511 and 308 distinct miRNAs over all age comparisons, respectively.

“Especially the brain regions cerebellum and choroid plexus stood out with 511 and 308 distinct miRNAs over all age comparisons, respectively.”

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

For the aging cohort, 844 samples were sequenced and 1966 miRNAs were obtained before filtering.

“For the aging cohort, we obtained 844 sequenced samples and 1966 miRNAs (9139 lncRNAs, 30930 piRNAs, 356 rRNAs, 51 scaRNAs, 1542 snoRNAs, 1390 snRNAs and 408 tRNAs) from which we kept 828”

May combine two claims.

MiR-212-3p was significantly anti-correlated with age in males and miR-3473e in females, both for two brain regions.

“MiR-212-3p was significantly anti-correlated with age in males and miR-3473e in females, both for two brain regions, namely olfactory bulb and corpus callosum, hippocampus anterior and olfactory bulb, respectively.”

May combine two claims.

11 miRNAs were significantly anti-correlated (e.g., miR-18a-5p in olfactory bulb and pons) and 7 were significantly positively correlated in multiple tissues (e.g., miR-155-5p in corpus callosum, mot. cortex, caudate putamen, medulla, choroid plexus, SVZ, thalamus, and vis. cortex).

“We found 11 miRNAs significantly anti-correlated (e.g., miR-18a-5p in olfactory bulb and pons) and 7 significantly positively correlated in multiple tissues (e.g., miR-155-5p in corpus callosum, mot. cortex, caudate putamen, medulla, choroid plexus, SVZ, thalamus, and vis. cortex).”

May combine two claims.

IsomiRs of miR-155-5p followed a similar trend of increase during aging in all regions, but the archetype form dominated.

“We found that isomiRs of miR-155-5p followed a similar trend of increase during aging in all regions, but the archetype form dominated (Fig. 5g, Supplementary Fig. 10a).”

May combine two claims.

Neither sex nor age can be identified as strong factors driving distinct grouping in UMAP visualization of young adult mice.

“Neither sex nor age can be identified as strong factors driving a distinct grouping in the UMAP visualization (Supplementary Fig. 2g and 2h).”

May combine two claims.

In females, 76 significantly positively age-correlated miRNAs were observed and a matching high count of upregulated miRNAs is observed within age comparisons across all regions.

“In females, we observed 76 significantly positively age-correlated miRNAs (Fig. 3b) and a matching high count of upregulated miRNAs is observed within the age comparisons across all regions (Fig. 3d).”

May combine two claims.

Cyclin H (CCNH) and the basic helix-loop protein (ARNLT) were significantly anti-correlated in five and six different regions, respectively.

“Cyclin H (CCNH) and the basic helix-loop protein (ARNLT) were significantly anti-correlated in five and six different regions, respectively.”

May combine two claims.

For miRNAs, age as an independent factor introduced 0.6% of variation and 3.8% in combination with brain region.

“Age, as an independent factor, introduced 0.6% of the variation and 3.8% in combination with the brain region.”

May combine two claims.

SVZ, choroid plexus, and pons shared 11 miRNAs, the highest number of shared miRNAs and regions.

“SVZ, choroid plexus, and pons shared 11 miRNAs, comprising the highest number of shared miRNAs and regions.”

May combine two claims.

During aging, miR-9-5p expression in the olfactory bulb slightly decreased over the lifespan in males but remained mostly stable in females.

“However, the expression in the olfactory bulb slightly decreased over the lifespan in males but remained mostly stable in females.”

May combine two claims.

Thalamus and corpus callosum exhibited solely sex-driven variances above 10% but equally strong solely age-driven variances.

“Thalamus and corpus callosum also exhibited solely sex-driven variances above 10% but equally strong solely age-driven variances.”

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

For the aDR study, 118 samples were sequenced and 113 were kept after filtering.

“This resulted in 118 sequenced and 113 kept samples for the aDR study”

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

tRNA-Glu-TTC-1-1 was significantly positively correlated with age in both sexes in multiple brain regions.

“We exemplary highlight a tRNA (tRNA-Glu-TTC-1-1), which was significantly positively correlated in both sexes in multiple brain regions (Fig. 1c).”

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

Cluster center lines containing trajectories from miR-5100 showed an increasing tendency.

“Looking at cluster center lines containing trajectories from miR-5100, we observed an increasing tendence (Supplementary Fig. 8c).”

May combine two claims.

In males, corpus callosum, visual cortex, and olfactory bulb were the most prominent regions affected by miRNA expression changes, as opposed to choroid plexus in females.

“In males, corpus callosum, visual cortex, and olfactory bulb were the most prominent regions affected by miRNA expression changes, as opposed to choroid plexus in females.”

May combine two claims.

If a cluster has a high region-specificity, there are no more than two to three miRNA trajectory occurrences in most cases. In contrast, clusters with multiple miRNA trajectory occurrences tend to have lower region-specificity.

“If a cluster has a high region-specificity, there are no more than two to three miRNA trajectory occurrences in most cases. In contrast, clusters with multiple miRNA trajectory occurrences tend to have lower region-specificity.”

May combine two claims.

MiR-155-5p, miR-146a-5p, and miR-5100 were significantly positively correlated with age in males and females.

“MiR-155-5p, miR-146a-5p, and miR-5100 were significantly positively correlated with age in males and females, exhibiting a strong aging signature independent from sex and region.”

May combine two claims.

MiR-155-5p and miR-146a-5p were expressed in microglia above a threshold of 3 rpmm, miR-5100 was not.

“MiR-155-5p and miR-146a-5p were expressed in microglia above a threshold of 3 rpmm, miR-5100 was not.”

May combine two claims.

In hippocampus posterior, 196 miRNAs were commonly downregulated at 26 and 28 months of age, even though no significantly anti-correlated miRNA was found.

“In hippocampus posterior 196 miRNAs were commonly downregulated at 26 and 28 months of age, even though no significantly anti-correlated miRNA was found.”

May combine two claims.

In sex-separated analysis, the most pronounced miRNA expression changes in females were in choroid plexus, SVZ, and hippocampus; in males, expression changes in the visual cortex, olfactory bulb, and corpus callosum dominated.

“In sex-separated analysis, we found the most pronounced miRNA expression changes in females in choroid plexus, SVZ, and hippocampus. While in males, expression changes in the visual cortex, olfactory bulb, and corpus callosum dominated.”

May combine two claims.

We reproduced previous findings of miR-200 exclusively expressed in olfactory bulb in males and extend this knowledge to equal region-specific expression in females.

“We reproduced previous findings of miR-200 exclusively expressed in olfactory bulb in males and extend this knowledge to equal region-specific expression in females.”

May combine two claims.

In males, 12 miRNAs were significantly positively correlated in the vis. cortex and 12 miRNAs were significantly anti-correlated in olfactory bulb.

“In males, 12 miRNAs were significantly positively correlated in the vis. cortex and in olfactory bulb 12 miRNAs were significantly anti-correlated (Fig. 3b, Supplementary Data 4).”

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

MiR-9-5p is highly expressed in all regions, though it is not amongst the 50 most variable miRNAs.

“MiR-9-5p is highly expressed in all regions (Supplementary Fig. 2j), though it is not amongst the previously defined 50 most variable miRNAs (Supplementary Fig. 2i).”

May combine two claims.

In our dataset, we discovered altered isomiR expression for miR-155-5p and an expression change in a target gene (CISH) exclusively in medulla.

“In our dataset, we discovered altered isomiR expression for miR-155-5p and an expression change in a target gene (CISH) exclusively in medulla.”

May combine two claims.

In females, cerebellum exhibited an even higher upregulation trend starting at 12 months of age with 451 upregulated miRNAs, but no significant age-correlated miRNAs were observed.

“While the cerebellum exhibited an even higher upregulation trend in females starting at 12 months of age with 451 upregulated miRNAs, no significant age-correlated miRNAs were observed.”

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

We found an average read count per sample of over 21 million for aDR and 23 million for YMP.

“We found an average read count per sample of over 21 million for aDR and 23 million for YMP (Supplementary Fig. 9d and 9e).”

May combine two claims.

For females, the signature is less pronounced, but a distinct expression of miR-200 family members persisted (miR-200b/c-5p).

“For the females, the signature is less pronounced, but a distinct expression miR-200 family members persisted (miR-200b/c-5p).”

May combine two claims.

Neither sex nor age was identified as strong drivers for grouping in the UMAP visualization of features.

“Neither sex nor age was identified as strong drivers for grouping (Supplementary Fig. 1d and 1e).”

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

In the mTOR pathway, 67 genes are included.

“In the mTOR pathway are 67 genes included45.”

• cites [45] Schaefer, C. F. et al. PID: the pathway interaction database. Nucleic Acids Res. 37, D674–D679 (2009). sourceNot checked yet

  Queued — the background check reaches it, usually within a day.

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

Limitations of our study include restricted transferability to humans and technical challenges of analysis of cell-type specific miRNA patterns.

“Limitations of our study include, aside from restricted transferability to humans, the limitations arising from technical challenges of analysis of cell-type specific miRNA patterns.”

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

Both miR-155-5p and miR-146a-5p regulate neuroinflammation and are implicated in neurodegenerative diseases.

“Given that both miR-155-5p and miR-146a-5p regulate neuroinflammation and are implicated in neurodegenerative diseases28, their roles in brain aging present compelling targets for further investigations.”

• cites [28] Danka Mohammed, C. P., Park, J. S., Nam, H. G. & Kim, K. MicroRNAs in brain aging. Mech. Ageing Dev. 168, 3–9 (2017). sourceNot checked — no full text of the source

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

On average, over 55% of the reads were mapped to miRNAs and 113 of 118 samples (96%) for aDR and 68 of 84 (81%) for YMP passed our quality control.

“On average, over 55% of the reads were mapped to miRNAs (Supplementary Fig. 9f and 9g) and 113 of 118 samples (96%) for aDR and 68 of 84 (81%) for YMP passed our quality control (Supplementary Data 1).”

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

The aDR study with C3B6F1 mice was performed in accordance with FELASA recommendations and approved by the Landesamt für Natur, Umwelt und Verbraucherschutz, Nordrhein-Westfalen, Germany.

“The aDR study with C3B6F1 mice was performed in accordance with the recommendations and guidelines of the Federation of the European Laboratory Animal Science Association (FELASA), with all protocols approved by the Landesamt für Natur, Umwelt und Verbraucherschutz, Nordrhein-Westfalen, Germany (84-02.04.2015.A437).”

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

These sex-specific changes potentially relate to sex-specific regulation of distinct pathways.

“These changes potentially relate to sex-specific regulation of distinct pathways.”

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

MiR-200 family members in the olfactory bulb are crucial to mediate neuronal maturation through targeting Zeb2 during postnatal development.

“MiR-200 family members in the olfactory bulb are crucial to mediate neuronal maturation through targeting Zeb2 during postnatal development22.”

• cites [22] Beclin, C. et al. miR-200 family controls late steps of postnatal forebrain neurogenesis via Zeb2 inhibition. Sci. Rep. 6, 35729 (2016). sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

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

Over 55% of reads mapped to miRNAs.

“over 55% of reads mapped to miRNAs (Supplementary Fig. 1b).”

Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

All experiments were performed in accordance with institutional guidelines approved by the VA Palo Alto Committee on Animal Research.

“All experiments were performed in accordance with institutional guidelines approved by the VA Palo Alto Committee on Animal Research.”

May combine two claims.

This indicates a strong expression decrease between 21 and 26 months, which was not detectable via correlation.

“This indicates a strong expression decrease between 21 and 26 months, which was not detectable via correlation.”

May combine two claims.

Age-related miRNAs occur in a region-dependent manner, but these miRNAs were not amongst the highest variable ones between all regions.

“In contrast, even though age-related miRNAs occur in a region-dependent manner, these miRNAs were not amongst the highest variable ones between all regions.”

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

828 of 844 samples (98%) passed quality control.

“828 of 844 samples (98%) passed quality control (Supplementary Data 1 and 2).”

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

It is possible that trends observed within the mouse data could be present in humans but cannot be captured during this short time course at the end of the human life span.

“As the youngest human age of 71 years roughly compares to the last time point of the mouse data (28 months), it is possible that the trends observed within the mouse data could be present in humans but cannot be captured during this short time course at the end of the human life span.”

• AssumptionRests on an assumption: The youngest human age of 71 years roughly compares to the last time point of the mouse data (28 months).

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

miRTargetLink 2.0 provided 82 target genes for mmu-miR-155-5p, considering all functional ones.

“miRTargetLink 2.043 provided 82 target genes for the feature mmu-miR-155-5p, considering all functional ones.”

• cites [43] Kern, F. et al. miRTargetLink 2.0-interactive miRNA target gene and target pathway networks. Nucleic Acids Res. 49, W409–W416 (2021). sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

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

Sex differences in pathologies as well as neural properties and associated mechanisms have been reported previously for caudate putamen, e.g., in humans for fiber connection strength.

“Sex differences in pathologies as well as neural properties and associated mechanisms have been reported previously for caudate putamen24, e.g., in humans for fiber connection strength.”

• cites [24] Wong, J. E., Cao, J., Dorris, D. M. & Meitzen, J. Genetic sex and the volumes of the caudate-putamen, nucleus accumbens core and shell: original data and a review. Brain Struct. Funct. 221, 4257–4267 (2016). sourceNot checked — no full text of the source

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

Exceptions like the overlap of hippocampus anterior and posterior can be explained by their anatomical and functional proximity.

“Exceptions like the overlap of hippocampus anterior and posterior can be explained by their anatomical and functional proximity.”

May combine two claims.

We chose to exclude CD45+ cells to distinguish resident microglia from infiltrating immune cells, thereby excluding a subset of resident microglia, as the expression of CD45 can increase with age in resident microglia.

“We chose to exclude CD45+ cells to distinguish resident microglia from infiltrating immune cells. However, we thereby exclude a subset of resident microglia, as the expression of CD45 can increase with age in resident microglia.”

• AssumptionRests on an assumption: The expression of CD45 can increase with age in resident microglia.

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

During sex-specific analysis, the study was limited to 14 brain regions and timepoints up to 21 months due to an insufficient number of older female samples.

“During sex-specific analysis, we were limited to 14 brain regions and timepoints up to 21 months due to an insufficient number of older female samples.”

May combine two claims.

Sex-specific miRNA expression patterns persist during the entire lifespan and dominate over age-related expression changes, especially strong in the motor cortex and caudate putamen.

“In summary, we found sex-specific miRNA expression patterns that persist during the entire lifespan and dominate over age-related expression changes, especially strong in the motor cortex and caudate putamen.”

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

All animal care and procedures complied with the Animal Welfare Act and were in accordance with institutional guidelines and approved by the institutional administrative panel of laboratory animal care at Stanford University.

“All animal care and procedures complied with the Animal Welfare Act and were in accordance with institutional guidelines and approved by the institutional administrative panel of laboratory animal care at Stanford University.”

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

On average, read count was over 9.5 million per group when aggregating all samples according to brain region and age.

“On average we found a read count of over 9.5 million per group, when aggregating all samples according to brain region and age (Supplementary Fig. 1a)”

May combine two claims.

In caudate putamen the miR-155-5p increase lead to a strong ARNTL decrease, whereas in medulla the decrease was less pronounced.

“In caudate putamen the miR-155-5p increase lead to a strong ARNTL decrease, whereas in medulla the decrease was less pronounced.”

May combine two claims.

miR-155-5p, miR-146a-5p, and miR-5100 are cross-sex brain aging miRNAs.

“These observations indicated miR-155-5p, miR-146a-5p, and miR-5100 as cross-sex brain aging miRNAs (Supplementary Data 9).”

May combine two claims.

These results indicate that expression is drastically increased between 12 and 15 months and remained constantly high thereafter.

“These results indicate that the expression is drastically increased between 12 and 15 months and remained constantly high thereafter.”

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

MiR-1 and miR-10b were previously reported to regulate BDNF, an important protein involved in synaptogenesis, memory, and learning.

“MiR-1 and miR-10b were previously reported to regulate BDNF (brain-derived neurotrophic factor) an important protein involved in synaptogenesis, memory, and leaning23.”

• cites [23] Varendi, K., Kumar, A., Harma, M. A. & Andressoo, J. O. miR-1, miR-10b, miR-155, and miR-191 are novel regulators of BDNF. Cell Mol. Life Sci. 71, 4443–4456 (2014). sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

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

In a previous study examining expression by bulk sequencing, peaks of deregulation at 12 and 18 months were observed in the brain without regional resolution.

“In our previous study, which examined the expression by bulk sequencing, we observed peaks of deregulation at 12 and 18 months in the brain without any regional resolution31.”

• cites [31] Wagner, V. et al. Characterizing expression changes in noncoding RNAs during aging and heterochronic parabiosis across mouse tissues. Nat. Biotechnol. 42, 109–118 (2024). sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

May combine two claims.

This atlas offers a comprehensive map of miRNA expression across different brain regions in a sex-specific manner, which was previously nonexistent.

“In sum, this atlas offers a comprehensive map of miRNA expression across different brain regions in a sex-specific manner, which was previously nonexistent”

May combine two claims.

Regional miRNA expression patterns occur in a sex independent manner in anterior and posterior brain regions, and strong sex-specific regional patterns rather occur in central brain regions (corpus callosum, motor cortex, choroid plexus, thalamus).

“Hence, we concluded that regional miRNA expression patterns occur in a sex independent manner in anterior and posterior brain regions, and strong sex-specific regional patterns rather occur in central brain regions (corpus callosum, motor cortex, choroid plexus, thalamus).”

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

For the aDR study with C57BL/6JN mice, 18-months-old mice were randomly assigned to AL or aDR.

“For the aDR study with C57BL/6JN mice, 18-months-old mice were randomly assigned to AL or aDR.”

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

Another limitation is the question of whether different microglial states in aDR and YMP exist with respectively specific miRNA expression patterns.

“Another limitation is the question of whether different microglial states in aDR and YMP exist with respectively specific miRNA expression patterns.”

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

Due to limited access to aged mice, especially females, this was not possible in this study. Therefore, also our microglia data is also limited to male samples.

“Due to limited access to aged mice, especially females, this was not possible in this study. Therefore, also our microglia data is also limited to male samples.”

Probably not a substantial claim: may not pass S2 (checkable).

The fact that these peaks were not observed across all brain regions in this study highlights the importance of a region-specific investigation.

“The fact that we did not observe these peaks across all brain regions in this study highlights the importance of a region-specific investigation.”