Restore And Relaunch Mitophagy With Urolithin A, A Microflora Metabolite of Pomegranate Ellagitannins

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Mitophagy

Mitophagy is critical for maintaining proper cellular functions.  1   It is the key in keeping the cell healthy. 

Mitophagy is the selective degradation of mitochondria by autophagy. It removes damaged mitochondria and often occurs to defective mitochondria following damage or stress.  However, mitophagy is not limited in damaged mitochondria but also involves undamaged mitochondria.

During aging the process of mitophagy slows down and begins to malfunction.  Due to this malfunction of the mitophagy process, worn-out or damaged mitochondria are not recycled and their decomposing components build up inside cells.  Over time, this malfunction may cause problems in various tissues. 

Evidence exists that malfunctioning mitophagy plays a role in certain diseases of aging including:

  • Parkinson’s disease 2 
  • Cancer  3

Mitophagy is critically important to good health for two reasons:  4  5

  • Mitochondria are one of the main sources of reactive oxygen species (ROS) generation and thus subject to ROS damage
  • Dysfunctional mitochondria that are not degraded via mitophagy produce higher amounts of ROS, thus amplifying ROS damage

It is therefore very important that the process of mitophagy is induced at all times, especially during the aging process.

Urolithin A for Mitophagy Restoration

Researchers from the École Polytechnique Fédérale in Lausanne (EPFL), Switzerland, published an article in the journal Nature Medicine on July 2016.  The name of the article is Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents.   The researchers showed that a compound called urolithin A prolonged lifespan in the nematode worm Caenorhabditis elegans and improved exercise capacity in older mice.  Caenorhabditis elegans worms that were exposed to urolithin A:

  • lived an average or 45% longer,  and
  • prevented the accumulation of dysfunctional mitochondria

When the researchers exposed rodents to urolithin A, there was an apparent and significant reduction in dysfunctional mitochondria.  The mice also improved their running endurance and capacity by 42% compared to mice not exposed to urolithin A.

The study revealed that urolithin A can restore and relaunch mitophagy when mitophagy is malfunctioning or becomes sluggish.

Urolithin A Precursor:  Ellagitannins

Urolithin A is not a natural substance that can be consumed.  Instead, it is a microflora human metabolite that is produced in the gastrointestinal tract via the digestion by intestinal bacteria.

Specifically, the precursor to urolithin A is a molecule in the family called the ellagitannins. Ellagitannins are a class of tannins, which is a type of polyphenol. 

Ellagitannins is a natural component of a number of foods, primarily found in red raspberry (Rubus idaeus).  

Once such ellagitannin is ellagic acid.  When ellagic acid is consumed via the diet, the the microflora bacteria in the gut breaks down the ellagic acid and produces urolithin A.  Thus, urolithin A is a microflora human metabolite of dietary ellagic acid derivatives.  

The highest levels of ellagic acid are found in:

  • blackberries
  • cranberries
  • grapes
  • Phellinus linteus  (medicinal mushroom)
  • pecans
  • pomegranates
  • raspberries
  • strawberries
  • walnuts
  • wolfberries

The École Polytechnique Fédérale in Lausanne (EPFL) study used urolithin A from pomegranate ellagitannins.  It appears that of the above listed foods, pomegranate has the greatest potential to produce the urolithin A metabolite from pomegranate ellagitannins.  6

Image result for pomegranate

Efficient Production of Urolithin A

The amount of urolithin A produced in the gastrointestinal tract is dependent on the gut’s microbiome enterotype.  The microbiome enterotype is the complete bacteriological ecosystem in the gut.  

If the gastrointestinal tract is in dysbiosis, then it’s ability to produce urolithin A from pomegranate ellagitannins is compromised.  This is why it is vitally important to create and maintain a symbiotic gastrointestinal tract.  The amount of urolithin A produced can vary widely, depending on whether the microbiome is in dysbiosis or is in symbiosis.

One of the main factors that create dysbiosis is long-term diet influences.  7 

Informational References:

Video – Pomegranates reveal its powerful anti-aging secret (École polytechnique fédérale de Lausanne (EPFL))

Resources:

Life Extension – Pomegranate Complete