Environmental signaling rescues aging muscle stem cells

This 2023 rodent study applied An environmental signaling paradigm of aging concepts to muscle stem cells:

“The stem cell niche environment represents an important therapeutic target to enhance tissue regeneration in aging. We decoupled age-related cell-intrinsic effects, niche-mediated cell-extrinsic effects, and changes in population dynamics of muscle stem cells (MuSCs) and two key muscle-resident cells in young and aged mice.

in vivo model

We showed that:

  1. Age-related reduction in MuSCs is not stochastic.
  2. Despite differences in transcriptomes of MuSC clusters, the effect of age on gene expression is largely uniform, suggesting that the niche environment has a fundamental role in age-related changes in MuSC gene expression.
  3. A significant fraction of changes in the transcriptome of aging MuSCs can be reversed by exposure to the young muscle environment, i.e. are niche-responsive. Given the high percentage [46.6% at a stringent cutoff of s-value < 0.05] of reversibility in gene expression, our findings indicate that age-related changes in the niche are principal drivers of resulting alterations in the MuSC transcriptome.
  4. Aging is correlated with changes at the level of chromatin accessibility and DNA methylation in MuSCs.

Plasticity of the MuSC transcriptome suggests that modulating the niche environment can be a powerful tool to restore stem cell-mediated endogenous muscle regeneration in aging. Consequently, as opposed to focusing solely on MuSCs themselves to mitigate effects of aging on MuSCs, bioengineering of the niche in its entirety may be a viable therapeutic option.”

https://www.nature.com/articles/s41467-023-36265-x “Transcriptional reprogramming of skeletal muscle stem cells by the niche environment”

This study destroyed extremely well-funded directed research efforts that detract from science, especially those promoting irreversibility of epigenetic changes (but: Rockefeller) and randomness of pro-aging programming (but: Harvard).

These researchers showed they could do more with their ideas and careers than maintain an outdated and easily disproved status quo.


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