Old mice regain leg strength after antibody treatment, Stanford Medicine researchers find

With our lost muscle strength our doctors and hospital should be initiating human research on this. But that won't occur, they have proven themselves incompetent for decades. I'm sure your hospital did nothing with this earlier research.

• CD47 (1 posts to July 2016)

• muscle stem cells (2 posts to June 2017)

The Stanford article here: 

Old mice regain leg strength after antibody treatment, Stanford Medicine researchers find

The actual research here:

Elevated CD47 is a hallmark of dysfunctional aged muscle stem cells that can be targeted to augment regeneration

• Ermelinda Porpiglia
• Thach Mai
• Peggy Kraft
• 
  
• Peter K. Jackson
• Wendy J. Fantl
• Helen M. Blau ⁸
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Published:November 15, 2022DOI:https://doi.org/10.1016/j.stem.2022.10.009

Highlights

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  Elevated CD47 levels define a dysfunctional aged muscle stem cell (MuSC) subset
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  U1 snRNA upregulation drives CD47 alternative polyadenylation in aged MuSCs
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  Thrombospondin-1/CD47 paracrine signaling suppresses aged MuSC proliferation
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  In vivo thrombospondin-1 blockade restores regeneration and strength in aged muscle

Summary

In aging, skeletal muscle strength and regenerative capacity decline, due in part to functional impairment of muscle stem cells (MuSCs), yet the underlying mechanisms remain elusive. Here, we capitalize on mass cytometry to identify high CD47 expression as a hallmark of dysfunctional MuSCs (CD47^hi) with impaired regenerative capacity that predominate with aging. The prevalent CD47^hi MuSC subset suppresses the residual functional CD47^lo MuSC subset through a paracrine signaling loop, leading to impaired proliferation. We uncover that elevated CD47 levels on aged MuSCs result from increased U1 snRNA expression, which disrupts alternative polyadenylation. The deficit in aged MuSC function in regeneration can be overcome either by morpholino-mediated blockade of CD47 alternative polyadenylation or antibody blockade of thrombospondin-1/CD47 signaling, leading to improved regeneration in aged mice, with therapeutic implications. Our findings highlight a previously unrecognized age-dependent alteration in CD47 levels and function in MuSCs, which underlies reduced muscle repair in aging.

Graphical abstract

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