Going to bat against inflammaging

Protein found in bats could tackle inflammation – and aging.

In the quest to unlock the secrets of aging, scientists have turned their attention to a rather unexpected source: bats. Recent research by scientists at Duke-NUS Medical School suggest that these small winged mammals possess a remarkable ability to combat inflammation, a process closely associated with aging and age-related diseases. In the latest research, a novel molecule called ASC2 has emerged as a promising player in inhibiting inflammasomes, key molecular complexes responsible for triggering inflammation.

Longevity.Technology: Inflammation, a vital response by the immune system to injury or infection, is a double-edged sword. While acute inflammation serves as a protective mechanism, chronic inflammation can lead to a host of health issues, including cardiovascular disease, cancer and neurodegenerative disorders. In recent years, scientists have been focusing on the concept of “inflammaging,” the chronic low-grade inflammation that accompanies aging. It is believed that inflammaging plays a significant role in the development and progression of age-related diseases.

Now, researchers have discovered that bats possess a unique ability to naturally control inflammation. The latest study, published in Cell, highlights the potential of a specific molecule called ASC2, found in bat cells. ASC2 has demonstrated a powerful capability to inhibit inflammasomes; by suppressing inflammasomes, ASC2 effectively limits inflammation, leading to suggesting its potential for for combating inflammaging [1]. Inflammasomes are also implicated in functional decline in aging.

The research team were studying the unusual ability of bats to host viruses without suffering significant illness.

“Bats have attracted great attention as a likely reservoir of the SARS-CoV-2 virus responsible for the COVID-19 pandemic,” said Professor Wang Lin-Fa, from Duke-NUS’ Emerging Infectious Diseases (EID) Programme, the senior author of the study. “But this unique ability to host yet survive viral infections could also have a very positive impact on human health if we can understand and exploit how they achieve this [2].”

As part of findings, the team discovered ASC2’s powerful inflammasome-inhibiting ability.

“This suggests that the high-level activity of ASC2 is a key mechanism by which bats keep inflammation under control, with implications for their long lifespan and unique status as a reservoir for viruses,” explained Dr Matae Ahn, first author and co-corresponding author of the study [2].

Examination of the ASC2 protein in detail identified four amino acids in the molecule that were key to making the bat protein more effective at dampening inflammation than its corresponding human protein. This provides valuable insight for the development of drugs that can mimic the anti-inflammatory effect of the bat protein [1].

ASC2 also holds promise in the treatment of various inflammatory conditions. By specifically targeting inflammasomes, this molecule may offer a more targeted approach to managing inflammation, avoiding the drawbacks associated with broad immunosuppression. The development of ASC2-based therapies could revolutionize the treatment of chronic inflammatory diseases, offering new hope to scores of individuals worldwide.

As well as tackling diseases, the implications of these findings are interesting from a longevity perspective – if inflammation lies at the core of age-related diseases, could controlling it potentially extend human lifespan? Scientists are cautiously optimistic, as while further research is needed to fully understand the mechanisms at play and assess the translation of bat-based discoveries to humans, initial findings provide a promising foundation.

Professor Wang said: “We have filed patents based on this work and are exploring commercial partnerships for drug discovery. We are hoping to develop a new class of anti-inflammatory drugs for inflammasome-driven human diseases.” Wang added that he strongly believes that it is time to focus on the more promising aspects of what makes bats special “to help fight the human diseases of the future [2].”

One particular challenge in translating bat research to humans is the vast differences in lifespan. Bats, despite their small size, can live exceptionally long lives compared with other mammals of similar size. This unique longevity suggests that bats may have evolved specialized mechanisms to combat aging-related processes, including inflammation. By studying and harnessing these adaptations, scientists hope to uncover novel therapeutic strategies that could benefit human health – when it comes to longevity, research into these flying creatures could prove to be bat-tastic!

[1] https://www.cell.com/cell/fulltext/S0092-8674(23)00333-1
[2] https://www.eurekalert.org/news-releases/989033