Researchers identify protein required to maintain muscle mass and strength during aging.


Researchers have long wondered what causes people to lose muscle strength as they age and how exercise can prevent it from happening.  Now, McMaster University researchers have discovered a key protein required to maintain muscle mass and muscle strength during aging.  The team state that this finding means new and existing drugs targeting the protein may potentially be used to preserve muscle function during aging.  The opensource study is published in the journal Cell Metabolism.

The current study found that the body’s fuel gauge, AMP-activated protein kinase (AMPK), is vital to slow muscle wasting with aging.  The data findings showed that mice lacking AMPK in their muscle developed much greater muscle weakness than expected in a middle-aged mouse.  Instead these mice, which were the equivalent of being just 50 years old, had muscles like that of an inactive 100-year-old.

Previous studies have shown that AMPK activity in muscle is ‘dialed down’ with aging in humans, so this may be an important cause of muscle loss during aging, hypothesize the team. Earlier research from the lab has shown that this metabolic switch is turned on with exercise as well as using commonly-prescribed medications such as metformin and salicylate (the active ingredient in Aspirin).

The team state that the AMPK pathway can be turned on with intense exercise and commonly-used Type 2 diabetes medications.  They go on to add that by knowing that AMPK is vital for maintaining muscle mass with aging, they now plan to adapt exercise regimes and existing drugs to switch on AMPK in muscle more effectively. The researchers conclude that development of new selective activators of the AMPK pathway in muscle may also be effective to prevent muscle loss with aging.

Source:  McMaster University

The AMP-activated protein kinase (AMPK) activates autophagy, but its role in aging and fasting-induced muscle function has not been defined. Here we report that fasting mice lacking skeletal muscle AMPK (AMPK-MKO) results in hypoglycemia and hyperketosis. This is not due to defective fatty acid oxidation, but instead is related to a block in muscle proteolysis that leads to reduced circulating levels of alanine, an essential amino acid required for gluconeogenesis. Markers of muscle autophagy including phosphorylation of Ulk1 Ser555 and Ser757 and aggregation of RFP-LC3 puncta are impaired. Consistent with impaired autophagy, aged AMPK-MKO mice possess a significant myopathy characterized by reduced muscle function, mitochondrial disease, and accumulation of the autophagy/mitophagy proteins p62 and Parkin. These findings establish an essential requirement for skeletal muscle AMPK-mediated autophagy in preserving blood glucose levels during prolonged fasting as well as maintaining muscle integrity and mitochondrial function during aging.  AMPK Activation of Muscle Autophagy Prevents Fasting-Induced Hypoglycemia and Myopathy during Aging.   Steinberg et al 2015.

The AMP-activated protein kinase (AMPK) activates autophagy, but its role in aging and fasting-induced muscle function has not been defined. Here we report that fasting mice lacking skeletal muscle AMPK (AMPK-MKO) results in hypoglycemia and hyperketosis. This is not due to defective fatty acid oxidation, but instead is related to a block in muscle proteolysis that leads to reduced circulating levels of alanine, an essential amino acid required for gluconeogenesis. Markers of muscle autophagy including phosphorylation of Ulk1 Ser555 and Ser757 and aggregation of RFP-LC3 puncta are impaired. Consistent with impaired autophagy, aged AMPK-MKO mice possess a significant myopathy characterized by reduced muscle function, mitochondrial disease, and accumulation of the autophagy/mitophagy proteins p62 and Parkin. These findings establish an essential requirement for skeletal muscle AMPK-mediated autophagy in preserving blood glucose levels during prolonged fasting as well as maintaining muscle integrity and mitochondrial function during aging. AMPK Activation of Muscle Autophagy Prevents Fasting-Induced Hypoglycemia and Myopathy during Aging. Steinberg et al 2015.

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