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

• •
  Elevated CD47 levels define a dysfunctional aged muscle stem cell (MuSC) subset
• •
  U1 snRNA upregulation drives CD47 alternative polyadenylation in aged MuSCs
• •
  Thrombospondin-1/CD47 paracrine signaling suppresses aged MuSC proliferation
• •
  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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Muscle stem cells provide insight into treatment of muscular dystrophies and aging muscles

You will need this in conjunction with the shooting in the dark interventions/guidelines your doctor/therapist is doing. You will need lots of muscle mass to accomplish the millions of repetitions needed for your recovery. Even though no one in the world knows how many repetitions are exactly needed to accomplish recovery.  Your doctor should know exactly how much muscle atrophy is occurring and the protocols to correct it.

Your doctors' responsibility is to get you 100% recovered.  Ask for the protocols that will accomplish that. If your doctor states; 'All strokes are different, all stroke recoveries are different.' you have a doctor that understands nothing about stroke, fire him/her. 

Muscle stem cells provide insight into treatment of muscular dystrophies and aging muscles

 

Stem cells may be the key to staying strong in old age

You might need this in conjunction with the non-interventions your doctor is doing. You will need lots of muscle mass to accomplish the millions of repetitions needed for your recovery.
https://www.mdlinx.com/internal-medicine/medical-news-article/2017/06/12/muscle-stem-cells-old-age-age/7207947/?

University of Rochester Medical Center

University of Rochester Medical Center researchers have discovered that loss of muscle stem cells is the main driving force behind muscle decline in old age in mice. Their finding challenges the current prevailing theory that age–related muscle decline is primarily caused by loss of motor neurons. Study authors hope to develop a drug or therapy that can slow muscle stem cell loss and muscle decline in the future.

As early as your mid 30s, the size and strength of your muscles begins to decline. The changes are subtle to start – activities that once came easily are not so easy now – but by your 70s or 80s, this decline can leave you frail and reliant on others even for simple daily tasks. While the speed of decline varies from person to person and may be slowed by diet and exercise, virtually no one completely escapes the decline.

“Even an elite trained athlete, who has high absolute muscle strength will still experience a decline with age,” said study author Joe Chakkalakal, PhD, assistant professor of Orthopaedics in the Center for Musculoskeletal Research at URMC.

Chakkalakal has been investigating exactly how muscle loss occurs in aging mice in order to figure out how humans might avoid it.

In a study, published in the journal eLife, Chakkalakal and lead author Wenxuan Liu, PhD, recent graduate of the Biomedical Genetics Department at URMC, define a new role for stem cells in the life long maintenance of muscle. All adults have a pool of stem cells that reside in muscle tissue that respond to exercise or injury – pumping out new muscle cells to repair or grow your muscles. While it was already known that muscle stem cells die off as you age, Chakkalakal’s study is the first to suggest that this is the main driving factor behind muscle loss.

To better understand the role of stem cells in age–related muscle decline, Chakkalakal and his team depleted muscle stem cells in mice without disrupting motor neurons, nerve cells that control muscle. The loss of stem cells sped up muscle decline in the mice, starting in middle, rather than old age. Mice that were genetically altered to prevent muscle stem cell loss maintained healthier muscles at older ages than age–matched control mice.

At the same time, Chakkalakal and his team did not find evidence to support motor neuron loss in aging mice. Very few muscle fibers had completely lost connection with their corresponding motor neurons, which questions the long–held and popular “Denervation/Re–innervation” theory. According to the theory, age–related muscle decline is primarily driven by motor neurons dying or losing connection with the muscle, which then causes the muscle cells to atrophy and die.

“I think we've shown a formal demonstration that even for aging sedentary individuals, your stem cells are doing something,” said Chakkalakal. “They do play a role in the normal maintenance of your muscle throughout life.”

Chakkalakal is building on this discovery and searching for a drug target that will allow him to maintain the muscle stem cell pool and stave off muscle degeneration as long as possible and he hopes this discovery will help move the field forward.