More ARGK-1 Increases Nematode Life Span

There are many ways to extend life in short-lived nematode worms, but most overlap, being different ways to manipulate the same few core mechanisms. Everything in cellular biology connects to everything else, so isn't at all unexpected for there to be a dozen indirect ways to alter levels of any one particular protein, or alter the behavior of any one particular pathway. Much of the present focus in the aging research community involves mapping all of these methods so as to pin down the list of those core mechanisms, the most important ways in which metabolism determines variations in longevity between individuals and species. This actually has very little relevance to the future of human longevity and the development of rejuvenation treatments: those will emerge from efforts to repair the cell and tissue damage known to cause aging, an approach that will produce rejuvenation, not from altering the operation of metabolism to merely slightly slow down aging.

"We found that longevity can be extended by increasing the amount of a protein called arginine kinase-1 (ARGK-1). 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 S6 kinase (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 caught our attention because levels in S6K mutant worms were more than 30 times higher compared to normal worms. When we created normal worms that overexpressed ARGK-1, they also lived significantly longer, meaning that ARGK-1 on its own can extend life."

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. "Our main goal in studying aging is not to find ways to extend human lifespan, but to understand the processes by which our cells and tissues become less functional over time. Such insight might allow us to develop better preventive care that improves overall health at advanced ages, or interventions that can slow or perhaps even prevent the progression of diseases associated with aging. For example, in cancer, some tumors highly activate S6K to feed tumor growth. Further work to understand the relationship between creatine kinase and S6K may lead to new avenues to pursue novel drugs for age-related diseases, including cancer."



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