The researchers at University of Birmingham have found a unique relationship between AMP-activated protein kinase (AMPK) and the mechanism with which body clears damaged mitochondria.
The former can stimulate the clearance of the latter. This suggests AMPK activators such as exercise can be potentially beneficial in helping elderly people preserve their physical bodily functions longer. These findings were published in the Federation of American Societies for Experimental Biology Journal.
Delighted to announce that my first, first-author paper on AMPK-mediated mitophagy in skeletal muscle as of today, has been accepted in @FASEBJournal. Super excited to present this work @KeystoneSymp on Wednesday. Find me at P3010. @LaiYuChiang @MIBTP1 @UBSportExR #KSexercise pic.twitter.com/BHHyL1jgw1
— Alex Seabright (@alex_seabright) March 3, 2020
First, let’s us understand the complex relationship between the mitochondria and preservation of physical function in old adults.
Mitochondria are present in every human cell. It is an organelle where biochemical processes of respiration and energy production occur. Mitochondria are the powerhouses of cells. They take in nutrients absorbed by the body and break them down. This creates energy molecules for the body to use. Decline in its quality and activity is associated with aging and development of other age-related diseases.
Mitochondria can contribute to the aging processes through multiple means like chronic inflammation, cellular senescence, and age dependent decline in stem cell activity. One key aspect of this is the signaling pathways that regulate the mitochondrial unfolded protein response and mitophagy.
This is what the researchers wanted to understand — the relationship between mitophagy and the factors controlling it.
Mitophagy is the process by which cells selectively destroy and clear away the unwanted mitochondria. This usually happens after some type of stress damages the mitochondria. The synthesis and breakdown of the mitochondria occurs as body’s demand for energy changes.
In older adults, however, the way this breakdown occurs can change, leading to a build-up of old and damaged mitochondria. This can decline the function of a person’s muscles which in turn can limit their physical prowess.
What This Study Tells Us
The experimental study aimed to understand the relationship between AMPK and mitophagy in cells. The researchers used mouse skeletal muscle cell lines to perform their experiment. These cells were then treated with CCCP (carbonyl cyanide m‐chlorophenyl hydrazine) and adenosine monophosphate (AMP)–activated protein kinase (AMPK) activator 991.
The subsequent changes in the cells were observed using a new tool developed by the lead researcher Alex Seabright. This tool uses fluorescent tags to study mitochondria changes. When the networks of mitochondria are healthy, they appear gold in color, but when cells break down mitochondria, the color appears red.
They found out that AMPK activators help stimulate mitochondrial break down. They saw that AMPK activation promotes the process of mitophagy by enhancing mitochondrial fission (division) and subsequent autophagosomal engulfment of this damaged matter. As exercise is an AMPK activator, it stands to reason that it can help prolong physical function in old adults with mitochondrial damage in their cells.
This can also be operationalized by formulating drugs that can activate AMPK, which can in turn clear away damaged mitochondria. The project leader, Dr Yu-Chiang Lai, says:
Many pharmaceutical companies are currently working to develop pre-clinical compounds that activate AMPK. We hope that our new discovery will accelerate targeted drug development to help identify new and safe compounds to activate this key molecule in muscle.
The study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC).
Elderly People and Physical Activity
World Health Organization estimates that globally 3.2 million deaths are due to physical inactivity. As it has been proven that physical activity is essential in elderly people, WHO has given its own recommendations for exercise for older adults of ages 65 and above. These recommendations include:
- At least 150 minutes of moderate aerobic activity or 75 minutes of vigorous aerobic activity should be adopted per week
- The aerobic activity that is performed should be at least of 10 minutes duration
- To enjoy additional benefits 300 minutes of moderate or 150 minutes of vigorous aerobic activity should be adopted
- Adults with poor mobility should do balance exercises on 3 or more dayseach week. This can help prevent falls
- Muscle strengthening activities should be performed two or more days each week
- If olderadults do not have the strength to perform these activities, they should do as much exercise as they are able to