Nitric Oxide and Longevity in Nematodes

Nitric oxide shows up in many places in the the biochemistry of longevity, the processes by which differences in the operation of metabolism influence the pace of aging. In this example, however, it isn't particularly clear that it has any great relevance to human biology:

Although humans and many other organisms have the enzyme needed to produce nitric oxide, C. elegans does not. Instead, [the] worm can "hijack" the compound from the soil-dwelling Bacillus subtilis bacterium that is not only a favored food but also a common colonist within its gut. This resourcefulness [partially] explains why worms fed B. subtilis live roughly 50 percent longer than counterparts fed Escherichia coli, which does not produce the compound.

In the new study, the average C. elegans lifespan increased by nearly 15 percent, to about two weeks, when researchers fed the worms nitric oxide-producing B. subtilis bacteria, compared to worms fed mutant B. subtilis with a deleted nitric oxide production gene. The research group also used fluorescent sensors to show that C. elegans does not make its own nitric oxide gas. When the worms were fed normal B. subtilis bacteria, however, the fluorescent signal appeared in their guts.

Fluorescent labeling and other tests also demonstrated that B. subtilis-derived nitric oxide penetrated the worms' tissues, where it activated a set of 65 genes. Some had been previously implicated in stress resistance, immune response, and increased lifespan, though others have unknown functions. Importantly, the researchers showed that two well-known regulatory proteins were essential for activating all of the genes.

"What we found is that nitric oxide gas produced in bacteria inside the worms diffuses into the worm tissue and activates a very specific set of genes acting through two master regulators, hsf-1 and daf-16, resulting in a high resistance to stress and a longer life. It's striking that a small molecule produced by one organism can dramatically affect the physiology and even lifespan of another organism through direct cell signaling."

Link: http://www.eurekalert.org/pub_releases/2013-02/jhm-jhr021213.php

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