Evidence map›Paper›PMID 36905126›Full record

ArticleJournal of cachexia, sarcopenia and muscle2023

Longitudinal transcriptomic analysis of mouse sciatic nerve reveals pathways associated with age-related muscle pathology.

Nicole Comfort, Meethila Gade, Madeleine Strait, Samantha J Merwin, Daphne Antoniou, Chiara Parodi, Lina Marcinczyk, Lea Jean-Francois, Tessa R Bloomquist, Anna Memou and 4 more

Open access · goldAbstract read
In one paragraph

Article in Journal of cachexia, sarcopenia and muscle, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
4.5field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 4 countries.

Nicole ComfortDepartment of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.ORCID 0000-0002-6827-3043
Meethila GadeDepartment of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
Madeleine StraitDepartment of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
Samantha J MerwinDepartment of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
Daphne AntoniouCenter for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Chiara ParodiDepartment of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
Lina MarcinczykDepartment of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
Lea Jean-FrancoisDepartment of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
Tessa R BloomquistDepartment of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
Anna MemouCenter for Clinical, Experimental Surgery, and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Hardy J RideoutCenter for Clinical, Experimental Surgery, and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Stefania CortiNeuroscience Section, Dino Ferrari Centre, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
Shingo KariyaDepartment of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Diane B ReDepartment of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
Columbia University · USAcademy of Athens · GRBiomedical Research Foundation of the Academy of Athens · GRMotor Neurone Disease Association · GBUniversity of Milan · IT

Funding

Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3M
True Metal fac coreP30ES009089 · NIEHS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MATTHEW S PERZANOWSKI · 1998 to 2026
$44.7M
Toward Understanding Aging Mechanisms of Neuromuscular JunctionsR21AG052011 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI RE, DIANE BERENGERE · 2016 to 2017
$440k
Air Pollution, Salivary Extracellular Vesicles, and Asthma Severity in Children with AsthmaF31ES030973 · NIEHS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI COMFORT, NICOLE · 2020 to 2021
$39k
NCI NIH HHS P30 CA013696NIA NIH HHS R21 AG052011NIEHS NIH HHS F31 ES030973NIEHS NIH HHS P30 ES009089
6 · The paper itself

Abstract

backgroundSarcopenia, the age-associated decline in skeletal muscle mass and strength, has long been considered a disease of muscle only, but accumulating evidence suggests that sarcopenia could originate from the neural components controlling muscles. To identify early molecular changes in nerves that may drive sarcopenia initiation, we performed a longitudinal transcriptomic analysis of the sciatic nerve, which governs lower limb muscles, in aging mice.

methodsSciatic nerve and gastrocnemius muscle were obtained from female C57BL/6JN mice aged 5, 18, 21 and 24 months old (n = 6 per age group). Sciatic nerve RNA was extracted and underwent RNA sequencing (RNA-seq). Differentially expressed genes (DEGs) were validated using quantitative reverse transcription PCR (qRT-PCR). Functional enrichment analysis of clusters of genes associated with patterns of gene expression across age groups (adjusted P-value < 0.05, likelihood ratio test [LRT]) was performed. Pathological skeletal muscle aging was confirmed between 21 and 24 months by a combination of molecular and pathological biomarkers. Myofiber denervation was confirmed with qRT-PCR of Chrnd, Chrng, Myog, Runx1 and Gadd45ɑ in gastrocnemius muscle. Changes in muscle mass, cross-sectional myofiber size and percentage of fibres with centralized nuclei were analysed in a separate cohort of mice from the same colony (n = 4-6 per age group).

resultsWe detected 51 significant DEGs in sciatic nerve of 18-month-old mice compared with 5-month-old mice (absolute value of fold change > 2; false discovery rate [FDR] < 0.05). Up-regulated DEGs included Dbp (log

conclusionsGene expression changes in mouse peripheral nerve were detected prior to disturbances in myofiber innervation and sarcopenia onset. These early molecular changes we report shed a new light on biological processes that may be implicated in sarcopenia initiation and pathogenesis. Future studies are warranted to confirm the disease modifying and/or biomarker potential of the key changes we report here.

Indexed as

Biological PhenomenaSarcopeniaAnimalsCross-Sectional StudiesFemaleMiceMice, Inbred C57BLMuscle, SkeletalReceptors, CholinergicSciatic NerveTranscriptomeChrnd protein, mouseReceptors, Cholinergicagingfrailtymotor unitRNA-seqsarcopeniaskeletal muscle

Identifiers

PMID36905126
PMCPMC10235898
OpenAlexW4323921212

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.