Stem Cell Biology of Aging

Research topic(s)

Skeletal muscle serves a multitude of functions in the organism and exhibits a remarkable
ability to adapt to physiological demands. Satellite cells are the stem cells of skeletal
muscle and are associated with its growth, maintenance and regeneration. Aged skeletal
muscle shows a significantly impaired regenerative potential. Evidence in the literature
suggests that functionality of satellite cells in aged skeletal muscle is impaired due to the
aged environment, but also due to intrinsic differences between adult and aged satellite
cells. Our lab investigates the intrinsic differences between adult and aged satellite cells,
especially the satellite stem cell subpopulation. This work will provide insights into
pathways, which are perturbed in aged satellite cells and allow for modification of these
pathways thereby rejuvenating aged muscle.
To assess the functionality of satellite cells during aging, we analyze injured skeletal
muscles from aged and adult mice and investigate the regeneration process at different
time points after injury. We could already show that JAK/STAT-signaling is upregulated in
aged satellite cells leading to impaired regeneration in aged skeletal muscle.

The ultimate goal in the treatment of sarcopenia – the age-related reduction in muscle
mass and functionality – is to preserve muscle mass and restore satellite cell homeostasis.
When the homeostasis of a tissue is perturbed this likely leads to its degeneration. A factor
that can restore the differentiation potential of satellite cells and their ability to self-renew in
the aged has the potential to reinstate tissue homeostasis in old skeletal muscle. Therefore
we propose to perform a screen to determine such factors using single fiber cultures from
aged mice.

Methods

• Single myofiber cultures
• in vivo injury of adult murine skeletal muscle with cardiotoxin

Selected Publications

Schmidt M, Weidemann A, Poser C, Bigot A, von Maltzahn J. (2021) Stimulation of non-canonical NF-κB through lymphotoxin-β-receptor impairs myogenic differentiation and regeneration of skeletal muscle.External link Front Cell Dev Biol, 9:721543

Schüler SC, Kirkpatrick JM*, Schmidt M*, Santinha D, Koch P, Di Sanzo S, Cirri E, Hemberg M, Ori A, von Maltzahn J#. (2021) Extensive remodeling of the extracellular matrix during aging contributes to age-dependent impairments of muscle stem cell functionality.External link Cell Rep, 35(10):109223 (* equal contribution, # cosenior authors)

Schmidt M, Poser C, von Maltzahn J. (2020) Wnt7a counteracts cancer cachexia.External link Mol Ther Oncolytics, 16:134-146

Ahrens HE*, Huettemeister J*, Schmidt M, Kaether C, von Maltzahn J. (2018) Klotho expression is a prerequisite for proper muscle stem cell function and regeneration of skeletal muscle.External link Skelet Muscle, 8(1):20

Schwoerer S, Becker F, Feller C, Koeber U, Henze H, Baig A, Kaus JM, Xin B, Lechel A, Lipka DB, Schmidt M, Rohs R, Aebersold R, Medina KL, Kestler HA, Neri F, von Maltzahn J*, Tuempel S*, Rudolph KL*. (2016) Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals.External link Nature, 540(7633):428-432

Links

Learn moreExternal link