The principal investigators are Monica Driscoll, associate professor in Rutgers' department of molecular biology and biochemistry, and her Einstein collaborator, David Hall. Together with postdoctoral fellows Laura Herndon and Peter Schmeissner, their team looked at what actually happens as C. elegans grows old.
C. elegans is popular as an experimental model system - an organism simple to study, easy to manipulate and having biological elements parallel enough to humans to draw comparisons. This is the same nematode worm whose genetics were studied by three of this year's Nobel Prize winners. While much is known of the worm's genes and mutations affecting longevity, virtually nothing was known about what happens to its cells and tissues as the animal ages. The team's observations focused on this unexplored area.
In the muscle tissues, the scientists observed an age-related condition known as sarcopenia, characterized by a progressive loss of muscle mass and strength over time. Genetic analysis showed that a specific enzyme, age-1/PI3 kinase, plays an important role in this muscle deterioration. The investigators already knew that mutant worms lacking this enzyme live longer. This was the first demonstration, however, that the enzyme had to be present for age-related muscle deterioration to take place. The work raises the possibility that decline of one tissue type may drive the aging of the entire organism.
Sarcopenia, Driscoll and Hall point out, is also characteristic of aging in humans and the researchers were somewhat surprised to see its effects in the worms. Their observations suggest that genetic analysis of sarcopenia genes in C. elegans may have the potential to address crucial questions of molecular mechanisms in human sarcopenia, a major problem in human health.
"Once you have figured out what a key molecule is doing in the worm, you can look for it in humans and expect the same things to happen," said Driscoll. "All the basic machinery is there, and the way things work in the worm is the way things work in people, though we are a bit more complicated with a few more bells and whistles."
Given the strong parallels the researchers noted between nematode and human sarcopenia, the human potential is obvious, said Driscoll. "You don't necessarily need to fix everything, but we can now imagine making a few key adjustments that can actually make us live with a more youthful muscle profile for longer.
"Ultimately, we would like to be in a position to engineer or adjust the chemistry of the body so that you can extend the period of health and delay some of the unwanted aspects of aging," Driscoll continued. "The long-term goal is to regulate the responsible biochemical pathway through drug therapy. In this way, we could maintain the health of the muscle based on the lessons the little worm taught us."
"Another striking aspect of the biology of aging in nematodes is the wide variability in the rate and time of onset for deterioration in different cells and tissues," said Hall, an associate professor in Einstein's department of neuroscience. He explained that apparently each cell is subject to random events that can trigger it to begin the aging process apart from what is happening in other tissues of the same animal. "We suspect that similar random events can also provoke the aging process in humans, and we plan to test protective strategies by using the worm as our model system," he said.
Karen Gardner at Albert Einstein College of Medicine