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Hallmarks of aging
Research brief

Abstract: Candidate INHBA/Activin A macrophage–muscle stem cell axis in aged human muscle

In an abstract integrating bulk and single-cell RNA data plus an older adult cohort, the authors propose a candidate INHBA/Activin A signal from inflammatory macrophages to early-primed muscle stem cells in aged human muscle; Activin A effects in primary human muscle stem cells were attenuated by SB431542. [1]

Automatic summary · not editorially reviewed

The key findings

  1. Bulk analysis of aged human muscle showed inflammatory activation, reduced mitochondrial and metabolic programmes and increased macrophage-associated signatures. [1]

  2. Ligand-target modelling prioritized INHBA/Activin A as a candidate signal from inflammatory macrophages to the aged early-primed muscle stem cell programme. [1]

  3. In primary human muscle stem cells, Activin A induced Activin-responsive genes and suppressed myogenic regulators, effects attenuated by the ALK4/5/7 inhibitor SB431542. [1]

The source at a glance

Study type / format
Integrated bulk and single-cell RNA-sequencing analysis with an independent cohort and primary cell experiments (abstract).
Population / context
Human skeletal muscle, including aged muscle, older adult single-cell cohorts and primary human muscle stem cells.
Summary based on
Study abstract
Original publication
September 17, 2026

Aged human muscle transcriptomes and single-cell states

The abstract describes an integrated analysis of bulk RNA sequencing, single-cell RNA sequencing and an independent older adult cohort to characterise age-associated changes in human skeletal muscle. Bulk analysis showed inflammatory activation, reduced mitochondrial and metabolic programmes, and increased macrophage-associated signatures in aged muscle. Single-cell analysis resolved distinct myeloid and muscle stem cell states. Among aged myeloid populations, inflammatory macrophages had the highest SenMayo score, and donor-level pseudobulk analysis identified age-related remodelling of early-primed muscle stem cells involving inflammatory, interferon-related and extracellular matrix programmes.

Supporting source [1]

Candidate INHBA/Activin A link and inhibitor test

Ligand-target modelling prioritized inhibin subunit beta A (INHBA)/Activin A as a candidate signal linking inflammatory macrophages to the aged early-primed muscle stem cell programme. An independent older adult human muscle single-cell cohort showed concordant INHBA expression in inflammatory macrophages and Activin receptor expression in early-primed muscle stem cells. In primary human muscle stem cells, Activin A induced Activin-responsive genes and suppressed myogenic regulators; these effects were attenuated by SB431542, a small-molecule inhibitor of ALK4/5/7 signalling. The authors describe this as a candidate communication framework, not an established causal mechanism.

Supporting source [1]

Abstract-only scope of the proposed framework

The findings are presented as supporting a candidate INHBA-associated, cell-state-resolved communication framework between inflammatory macrophages and early-primed muscle stem cell remodelling in aged human muscle, a potential link between immune remodelling and altered regenerative cell states. This is an abstract; the full text was not reviewed. Sample sizes, donor numbers, follow-up and detailed methods are not reported here, and the proposed framework is not a validated clinical tool. Associations and cell-culture inhibitor effects do not establish cause or a human lifespan or regeneration benefit.

Supporting source [1]

How to interpret this

Abstract only; the full text was not reviewed. Donor numbers, sample sizes, follow-up and detailed methods are not reported. The INHBA/Activin A axis is a candidate framework, and cell-culture inhibitor results do not establish causation or a human benefit.

Based on the study abstract; the full paper, tables and supplementary data were not reviewed.

Source & supporting passages

Read the quoted passagesIn the language of the original source
  1. Finding 1 ↑

    inflammatory activation, reduced mitochondrial and metabolic programmes
  2. Finding 2 ↑

    prioritized inhibin subunit beta A (INHBA)/Activin A
  3. Finding 3 ↑

    these effects were attenuated by SB431542

AI-assisted summary with linked source passages. No independent editorial or clinical review.

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