The collaborative research published in the journal Cell Reports draws on discovery of 2 major pathways governing aging in the nematode worm commonly used as a model in aging research because it shares many genes with humans and the short lifespan allows for quick assessment of effects on genetics and environmental interventions to extend healthy lifespan.
These pathways have been passed down to humans via evolution and are the subject of intensive research efforts, and a number of drugs are under development that may extend healthy lifespan by altering these pathways; discovery of the synergistic effect may pave the way to even more effective anti-aging therapies.
A double mutant was used in this study in which insulin signalling and TOR pathways have been genetically altered; altering of the IIS pathway yield a 100% increase in lifespan and alteration of the TOR pathway yields a 30% increase, the double mutant was expected to yield a 130% increase but instead it increased lifespan by 500%.
“Despite the discovery in C. elegans of cellular pathways that govern aging, it hasn’t been clear how these pathways interact,” said Hermann Haller, M.D., president of the MDI Biological Laboratory. “By helping to characterize these interactions, our scientists are paving the way for much-needed therapies to increase healthy lifespan for a rapidly aging population.”
“The synergistic extension is really wild,” said Rollins, who is the lead author with Jianfeng Lan, Ph.D., of Nanjing University. “The effect isn’t one plus one equals two, it’s one plus one equals five. Our findings demonstrate that nothing in nature exists in a vacuum; in order to develop the most effective anti-aging treatments we have to look at longevity networks rather than individual pathways.”
Discovery of the synergistic interaction may lead to the use of combination therapies to extend the healthy human lifespan in a similar manner as combination therapies are used to treat HIV and cancer. The interaction may also explain the inability to identify a single gene responsible for the ability of some to live to be centenarians free of major age related diseases.
The study focused on how longevity is regulated in mitochondria which is responsible for energy homeostasis. Accumulating evidence suggests a causative link between mitochondrial dysregulation and aging, future research will focus on further investigating the role of mitochondria in aging.
