Control of Inflammation May Contribute to the Longevity of Bats

Bat species tend to be very long lived in comparison to other mammalian species of a similar size. The usual explanation for this involves evolutionary adaptation to the metabolic demands of flight. Bats and birds exhibit similar biochemical and metabolic features, despite their evolutionary distance from one another. Bats may have evolved mitochondria, the power plants of the cell, that are more efficient and more resilient to oxidative damage than their closest mammalian relatives that do not fly, and it is generally acknowledged that mitochondrial function and metabolic rate are important determinants of species longevity.

Here, however, researchers argue for greater control over inflammatory responses to be a noteworthy contributing factor in the longevity of bats versus other small mammals. Chronic inflammation is certainly a major issue in human aging; the immune system becomes progressively ever more overactive and incapable. Inflammation is useful and necessary in short bursts, whether defending against pathogens or assisting in regeneration from injury, but those same mechanisms cause considerable harm when turned on all the time.

Bats live very long and host numerous viruses that are extremely harmful when they infect humans and other animals. Researchers wanted to find out how bats can harbour so many of these pathogens without suffering from diseases. The key, they found, is in the bat's ability to limit inflammation. Bats do not react to infection with the typical inflammatory response that often leads to pathological damage. In humans, while the inflammatory response helps fight infection when properly controlled, it has also been shown to contribute to the damage caused by infectious diseases, as well as to aging and age-related diseases when it goes into overdrive.

The researchers found that the inflammation sensor that normally triggers the body's response to fight off stress and infection, a protein called NLRP3, barely reacts in bats compared to humans and mice, even in the presence of high viral loads. The researchers compared the responses of immune cells from bats, mice and humans to three different RNA viruses - influenza A virus, MERS coronavirus, and Melaka virus. The inflammation mediated by NLRP3 was significantly reduced in bats compared to mice and humans.

Digging further, they found that 'transcriptional priming', a key step in the process to make NLRP3 proteins, was reduced in bats compared with mice and humans. They also found unique variants of NLRP3 only present in bats that render the proteins less active in bats than in other species. These variations were observed in two very distinct species of bats - Pteropus alecto, a large fruit bat known as the Black Flying Fox, and Myotis davadii, a tiny vesper bat from China - indicating that they have been genetically conserved through evolution. Further analysis comparing 10 bat and 17 non-bat mammalian NLRP3 gene sequences confirmed that these adaptations appear to be bat-specific. What this implies is that rather than having a better ability to fight infection, bats have a much higher tolerance for it. The dampening of the inflammatory response actually enables them to survive.

Link: https://www.duke-nus.edu.sg/news/duke-nus-researchers-discover-secret-bats%E2%80%99-immunity

Comments

Let's not forget that bats have to live in a constant state of calorie restriction. They cannot afford any fat or they would become too heavy for flight...

On the other hand...If the dampened reaction to infection is so beneficial why didn't the terrestrial animals evolve it too?

Posted by: cuberat at March 4th, 2019 7:06 AM

Perhaps they are safer from injury generally, and if a predator did catch them it would be game over anyway - no chance of escaping and healing. Or perhaps it is due to the types of pathogens they are prone to encountering.

Having hyperactive NLRP3 is supposed to offer some protection against Clostridium difficile and that has been suggested to be the reason the FMF gene variant persists.
http://stke.sciencemag.org/content/9/459/ec299

I might be a walking NLRP3 inflammasome activation assay kit. Stuff that seems to help reduce NLRP3 activation - progesterone, cannabidiol, vitex (orientin?), magnesium chloride, potassium, NO (beets or exercise).

Posted by: CD at March 4th, 2019 10:53 AM

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