Drug seems to mimic the biological effects of calorie restriction, letting worms live up to 70 percent longer.

A light micrograph of Caenorhabditis elegans, a soil-dwelling nematode often used in research.

The latest in a long line of longevity brews that prolong the lives of laboratory animals was described today in Nature: a natural molecule that extends life spans longer than any previous such agent, in some cases by as much as 70 percent.

“An internal fountain of youth,” is how lead investigator Jing Huang, a molecular biologist at the University of California, Los Angeles, described the compound, known as alpha-KG. In experiments on the roundworm Caenorhabditis elegans, she and her colleagues supplemented feedings with a handful of different chemicals involved in metabolism. The only one that had a significant effect on longevity was alpha-KG, which allowed worms to live about 25 days on average, compared with the typical 15 days. “It was an amazing hit,” Huang said.

Huang’s team was testing metabolic compounds in an effort to uncover the mechanism by which calorie restriction dramatically extends life spans in experimental animals, including C. elegans and mice. “Despite the fact that people have been studying it for decades, we still don’t really know at the molecular level how it happens,” said Matthew Gill, a biologist at the Scripps Research Institute in Jupiter, Florida, who was not involved in the new study.

Curbing Growth

Huang’s team learned that alpha-KG triggers several cellular processes that slow down metabolism. It curbs the activity of ATP, a molecule that transports energy inside a cell. It also decreases oxygen consumption and increases autophagy, a process in which the cell eats its own parts when food is in short supply. In other words, the alpha-KG seems to delay aging by switching the cell from growth mode to survival mode. This is thought to be how calorie restriction works as well, Huang said.

It’s far too soon to say whether alpha-KG will have any clinical use, said João Pedro de Magalhães, a biologist at the University of Liverpool who was not involved in the research. “There’s no evidence that this will work in mammals, much less in people,” he said.

But Huang has great hopes for the compound. She said that preliminary experiments in her lab suggest that alpha-KG will have similar effects on longevity in mice. “We are very excited about testing [it] in clinical trials” at some point in the future, she said. (Related: “The Secrets of Long Life.”)

Supplement Surprises

Still, it’s probably much too early to bet the house on alpha-KG, which is currently sold as a dietary supplement and sometimes marketed as a way to build muscles or boost athletic performance. The most important aspect of Huang’s study, according to Gill, is that it found a link between alpha-KG and ATP. By better understanding these molecular interactions, researchers might be able to find other compounds that also target ATP pathways and mimic alpha-KG’s effects. But, he added, that doesn’t mean alpha-KG itself “is necessarily going to be the thing that we all take to extend life span.”

Matt Kaeberlein
, a molecular biologist at the University of Washington in Seattle who was not involved in the work, agreed that the study doesn’t provide enough evidence to suggest anyone should start taking alpha-KG. The irony, he said, is that if the mechanism uncovered by Huang’s lab holds true in people, “those folks who are taking alpha-KG to promote muscle growth may actually be having the opposite effect.”

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