Impact of mtDNA Mutations on Age-Related Muscle Loss | 25 Dec 2024

Source: TH 

Why in News?  

A recent study published in Genome Research reveals that deletion mutations in mitochondrial Deoxyribonucleic Acid (mtDNA) contribute significantly to muscle loss with age.  

• Researchers found that these mutations impair mitochondrial function, leading to muscle degradation. This discovery offers potential pathways for delaying age-related muscle decline. 

What is Mitochondria? 

• About: Mitochondria are membrane-bound organelles found in the cytoplasm of most eukaryotic cells.  
  • Often referred to as the "powerhouses" of the cell, mitochondria are essential for producing energy needed for various cellular processes.  
  • Mitochondria are inherited exclusively from the mother through the egg cell. 
• Key Functions: 
  • ATP Production: Mitochondria generate adenosine triphosphate (ATP), the primary energy carrier in cells.  
    • ATP is crucial for almost all cellular functions, including muscle contraction, protein synthesis (process by which cells create proteins from DNA), and cell division. 
  • Cellular Respiration: Mitochondria are central to cellular respiration (break down food and release energy in the form of ATP). 
  • Regulating Cell Death: Mitochondria are involved in controlling apoptosis (type of cell death), which is important for maintaining healthy tissues and organs. 
• Mitochondrial DNA (mtDNA): Unlike most other organelles, mitochondria have their own DNA, known as mtDNA. 
  • mtDNA is prone to deletion mutations, where parts of the DNA are lost. These mutations can have significant consequences on cellular function. 
    • A deletion mutation in mtDNA makes the molecule smaller and less functional. Mutated mtDNA can outcompete healthy mtDNA during replication, causing a gradual decline in mitochondrial function. 

What are the Key Findings of the Study? 

• mtDNA Mutations: The study identifies that deletion mutations in mitochondrial DNA (mtDNA) play a significant role in the loss of muscle mass with age. 
• Dysfunction and Muscle Loss: Mutations impair mitochondrial function, causing muscle cells to struggle in generating enough ATP, leading to muscle cell death and atrophy. 
  • The study found that mtDNA deletions lead to the creation of chimeric genes (where two different mitochondrial genes fuse and form abnormal sequences).  
    • These chimeric genes disrupt the normal expression of mtDNA, further accelerating mitochondrial dysfunction. 
• Age-Related Changes: Researchers found that older individuals showed a two-fold increase in chimeric mitochondrial mRNA due to mtDNA deletions, which, along with abnormal gene expression, accelerated mitochondrial dysfunction and aging in muscle and brain tissues. 
• Biological Age Indicators: mtDNA deletion mutations and chimeric mRNA are valuable biomarkers for biological aging.  
  • Understanding their role could lead to therapies that prevent or repair these mutations, potentially delaying age-related muscle loss and other aging symptoms.