Scientists have identified a protein that can extend the natural lifespan of C. elegans, a microscopic roundworm commonly used for research on aging and longevity. The findings, published in Cell Reports, expand what we know about the aging process and may lead to new ways to delay the onset of human age-related diseases such as cancer and neurodegenerative diseases.
"We found that longevity can be extended by increasing the amount of a protein called arginine kinase-1 (ARGK-1)," said first author of the study. "ARGK-1 maintains ATP availability within cells, and we suspect that increased levels trigger a fuel sensor, regulating energy homeostasis and extending lifespan."
The research team identified ARGK-1 by comparing protein levels in normal worms to those in worms lacking (S6K), a genetic change that extends worm lifespan by at least 25%. Reduction of S6K proteins also extends lifespan significantly in several other organisms, including laboratory mice, showing that this pathway that controls aging is evolutionarily conserved.
ARGK-1 and its mammalian equivalent, creatine kinase, are enzymes that transport energy in the form of phosphoarginine or phosphocreatine to various locations within cells. The research team found that, as in worms, creatine kinase levels are increased in the brains of mice lacking a similar S6K protein.
Overexpression of ARGK-1 extends C. elegans lifespan, in part by activating the energy sensor AAK-2/AMPK. argk-1 is also required for the reduced body size and increased stress resistance observed in rsks-1/S6K mutants.
"Interestingly, supplements with creatine, the substrate for creatine kinase, have been found to improve health and longevity in mice and possibly provide beneficial effects to humans with Parkinson's disease, suggesting a potential role for these enzymes in aging and age-related diseases," added the author.
"Sorting out which cell functions are protected will be crucial for understanding exactly how ARGK-1 supports longevity in C. elegans, and potentially in other organisms as well."