Defending Against Environmental Stressors May Shorten Lifespan

A shorter life may be the price an organism pays for coping with the natural assaults of daily living, according to researchers at NIH and colleagues in Japan. The scientists used fruit flies to examine the relationship between lifespan and signaling proteins that defend the body against environmental stressors, such as bacterial infections and cold temperatures. 

Since flies and mammals share some of the same molecular pathways, the work may demonstrate how the environment affects longevity in humans.

Appearing in the Proceedings of the National Academy of Sciences, the research identified Methuselah-like receptor-10 (Mthl10), a protein that moderates how flies respond to inflammation. The finding provides evidence for one theory of aging, which suggests longevity depends on a delicate balance between proinflammatory proteins, thought to promote aging, and anti-inflammatory proteins, believed to prolong life. These inflammatory factors are influenced by what an organism experiences in its everyday environment.

Corresponding author Dr. Stephen Shears of NIEHS explained that Mthl10 appears on the surface of insect cells and acts as the binding partner to a signaling molecule known as growth-blocking peptide (GBP). 

Once Mthl10 and GBP connect, they initiate the production of proinflammatory proteins, which, in turn, shortens the fly’s life. However, removing the Mthl10 gene makes the flies unable to produce Mthl10 protein and prevents the binding of GBP to cells. As a result, the flies experienced low levels of inflammation and longer lifespans.

“Fruit flies without Mthl10 live up to 25 percent longer,” Shears said. “But, they exhibit higher death rates when exposed to environmental stressors.”

Shears said the research reveals that the ability of a young organism to defend against repeated environmental stress may be an empty victory, because the animal may not live as long. He believes the research may contribute to the discovery of drugs that target excess inflammation induced by signaling proteins in humans, extending life.