Published June 26, 2018 | FASEB Journal

It may come as little surprise that younger mice develop less liver damage from septic infections than older mice. But in discovering a mechanism that drives the difference, scientists in the Division of Critical Care Medicine may have opened the door to a new treatment for a condition that causes nearly 215,000 deaths a year in pediatric and adult intensive care units.

The researchers observed that young mice (2-3 months old) activate the AMPK protein in their livers in response to sepsis infection. However, this cell-protecting process is impaired in mature mice (11-13 months old).

“This protein initiates a machinery to maintain optimal mitochondrial function by promoting autophagy of damaged mitochondria and by promoting mitochondrial biogenesis, thus maintaining energy production,” says senior author Basilia Zingarelli, MD, PhD, the division’s Director of Basic Science Research.

Beyond identifying the protein involved, the team also identified a therapeutic agent that “could have a major impact in clinical intervention.”

Zingarelli’s team found that treatment with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) to activate AMPK reduced infection-induced liver damage in both younger and older mice.

Her team theorizes that AICAR ameliorates liver injury in mature animals by inducing robust gene transcription that repairs healthy mitochondria and removes damaged mitochondria.

More investigation is needed before human clinical trials can be launched, but Zingarelli notes that the potential benefits could be worth the effort.

Hospital care in the U.S. for patients with septicemia costs about $14 billion a year. While the sepsis mortality rate for children ranges from 5 to 10 percent, the rate rises up to 50 percent among those 65 and older.