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Muscle age and lifespan: beyond physiological strength

  • Data Source:National Health Research Institutes
  • Created:2020-10-30
  • Last Updated:2020-10-30

─NHRI has discovered a direct link between skeletal muscle aging and mortality through thermogenic and metabolic abnormalities─

 

October 30, 2020

Using genetic modified mouse models, research at the National Health Research Institutes (NHRI) has shown promise for advances in understanding the causal relationship between muscle aging, thermogenesis, and mortality.

Lamin A is a component of the nucleoskeleton. De novo mutation of human lamin A gene (i.e. LMNA) generated progerin protein, which is causal to the Hutchinson-Gilford progeria syndrome (HGPS). The aging process in HGPS patients is about 8 time faster than normal people. Dr. Chi and her team developed a mouse model which conditionally overexpressed with human progerin in muscle, and discovered that muscle‐specific overexpression of progerin was sufficient to induce muscular dystrophy and alter whole‐body energy expenditure, leading to premature death.

 The team found sarcolipin (Sln), an ER‐associated protein involved in heat production, is upregulated in the skeletal muscle expressing progerin. The depletion of Sln accelerated the early death of Lmna mutant mice. A further examination at the molecular level revealed that progerin recruits Sln and Calnexin to the nuclear periphery. Furthermore, progerin‐expressing myoblasts presented enhanced store‐operated Ca2+ entry. These findings suggested that progerin dysregulated calcium homeostasis through an interaction with a subset of ER‐associated proteins, resulting in thermogenic and metabolic abnormalities.

This research was recently published in Aging Cell. For the full text of the publication, see:

  1. Wang, W. P., Wang, J. Y., Lin, W. H., Kao, C. H., Hung, M. C., Teng, Y. C., Tsai, T. F. and Chi, Y. H. (2020) Progerin in muscle leads to thermogenic and metabolic defects via impaired calcium homeostasis. Aging Cell Feb;19(2):e13090.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996945/