Evidence map›Paper›PMID 40473693›Full record

ArticleNature communications2025

Complementing muscle regeneration-fibro-adipogenic progenitor and macrophage-mediated repair of elderly human skeletal muscle.

Jonas Brorson, Lin Lin, Jakob Wang, Amanda Bæk, Tine Borum Billeskov, Frederik Forsberg Thybo, Jesper Just, János Haskó, Christen Ravn, Rehne L Hansen and 5 more

Registry-linked trialAbstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03754842 (Effect of Nicotinamide Riboside and Pterostilbene Supplementation on Muscle Regeneration in Elderly Humans - A Randomized, Placebo-controlled, Clinical Trial), which is not on this map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
–field-weighted citation impact
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.

NCT03754842 nacompletednot on this map

Effect of Nicotinamide Riboside and Pterostilbene Supplementation on Muscle Regeneration in Elderly Humans - A Randomized, Placebo-controlled, Clinical Trial

TypeinterventionalSponsorUniversity of AarhusRan2019 to 2020Enrolled32ConditionsMuscle InjuryArmsPlacebo (twice daily), Nicotinamide Riboside/Pterostilbene (500 mg/100 mg twice daily)
3 · Its place in the literature

Who cites it

37 citing papers in PubMed.

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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

15 authors.

Jonas Brorson *Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.
Lin Lin *Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.ORCID http://orcid.org/0000-0002-7546-4948
Jakob WangSteno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.
Amanda BækSteno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.ORCID http://orcid.org/0009-0005-1500-5466
Tine Borum BilleskovSteno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.
Frederik Forsberg ThyboSteno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.ORCID http://orcid.org/0009-0001-4877-3593
Jesper JustDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0002-3825-0000
János HaskóDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.
Christen RavnDepartment of Orthopedic Surgery and Traumatology, Aarhus University Hospital, Aarhus, Denmark.
Rehne L HansenDepartment of Orthopedic Surgery and Traumatology, Aarhus University Hospital, Aarhus, Denmark.
Mats BueDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Jens Otto Lunde JørgensenDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0001-7408-1526
Yonglun LuoSteno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark. alun@biomed.au.dk.ORCID http://orcid.org/0000-0002-0007-7759
Niels JessenSteno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark. niels.jessen@biomed.au.dk.ORCID http://orcid.org/0000-0001-5613-7274
Jean FarupSteno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark. jean@biomed.au.dk.ORCID http://orcid.org/0000-0002-7579-6512

Funding

Det Frie Forskningsråd (Danish Council for Independent Research) 5053-00195Novo Nordisk Fonden (Novo Nordisk Foundation) NNF17OC0027242Novo Nordisk Fonden (Novo Nordisk Foundation) NNF23OC0085821
6 · The paper itself

Abstract

The capacity to regenerate skeletal muscle after injury requires a complex and well-coordinated cellular response, which is challenged in aged skeletal muscle. Here, we unravel the intricate dynamics of elderly human skeletal muscle regeneration by combining spatial, temporal, and single cell transcriptomics. Using spatial RNA sequencing (n = 3), we profile the expression of human protein-coding genes in elderly human skeletal muscle biopsies before as well as 2-, 8-, and 30-day post injury (NCT03754842). Single Cell-Spatial deconvolution analysis highlights monocytes/macrophages and fibro-adipogenic progenitors (FAPs) as pivotal players in human muscle regeneration. By utilizing flow cytometry (n = 9) and cell sorting we confirm the increased cellular content and activity during regeneration. Spatial correlation analysis unveils FAPs and monocytes/macrophages co-localization and intercellular communication, mediated by complement factor C3. Immunostaining confirms C3 expression in FAPs and FAP secretion of C3, suggesting a role in phagocytosis of necrotic muscle cells. Finally, functional assays demonstrate C3's impact on human monocyte metabolism, survival and phagocytosis, unveiling its involvement in skeletal muscle regeneration. These insights elucidate the FAP-macrophage interplay in aged human muscle with perspectives for future therapeutic interventions to reduce the age-induced decline in regenerative capacity.

Indexed as

MacrophagesMuscle, SkeletalRegenerationStem CellsAdipogenesisAgedAged, 80 and overAgingFemaleHumansMaleMonocytesPhagocytosisRandomized Controlled Trials as Topic

Identifiers

PMID40473693
PMCPMC12141666

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Registered trials

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.