Long-lived mitochondrial (Mit) mutants of Caenorhabditis elegans utilize a novel metabolism
The secret to a long life comes from how we extract energy from our food. Scientists compared one class of long-lived C. elegans, called the Mit mutants, with non-mutant wild type C. elegans. Their comparison showed significant metabolism changes, suggesting that their cellular engines had been reconfigured to run on new fuels and to make new waste products, leading to increased lifespans. The worms achieved long life through changes in how their cells extracted energy (metabolic state). Although C. elegans often is used as an animal model for human biology, more research is needed to determine if an equivalent metabolic state could be created in humans with the same results.
The Caenorhabditis elegans mitochondrial (Mit) mutants have disrupted mitochondrial electron transport chain (ETC) functionality, yet, surprisingly, they are long lived. We have previously proposed that Mit mutants supplement their energy needs by exploiting alternate energy production pathways normally used by wild-type animals only when exposed to hypoxic conditions. We have also proposed that longevity in the Mit mutants arises as a property of their new metabolic state. If longevity does arise as a function of metabolic state, we would expect to find a common metabolic signature among these animals. To test these predictions, we established a novel approach monitoring the C. elegans exometabolism as a surrogate marker for internal metabolic events. Using HPLC-ultraviolet-based metabolomics and multivariate analyses, we show that long-lived clk-1(qm30) and isp-1(qm150) Mit mutants have a common metabolic profile that is distinct from that of aerobically cultured wild-type animals and, unexpectedly, wild-type animals cultured under severe oxygen deprivation. Moreover, we show that 2 short-lived mitochondrial ETC mutants, mev-1(kn1) and ucr-2.3(pk732), also share a common metabolic signature that is unique. We show that removal of soluble fumarate reductase unexpectedly increases health span in several genetically defined Mit mutants, identifying at least 1 alternate energy production pathway, malate dismutation, that is operative in these animals. Our study suggests long-lived, genetically specified Mit mutants employ a novel metabolism and that life span may well arise as a function of metabolic state.—Butler, J. A., Ventura, N., Johnson, T. E., Rea, S. L. Long-lived mitochondrial (Mit) mutants of Caenorhabditis elegans utilize a novel metabolism.
If you liked this article, please give it a quick review on ycombinator or StumbleUpon. Thanks
Featured articles
Ocean Floor Gold and Copper
Ocean Floor Mining Company
Brian Wang is a Futurist Thought Leader and a popular Science blogger with 1 million readers per month. His blog Nextbigfuture.com is ranked #1 Science News Blog. It covers many disruptive technology and trends including Space, Robotics, Artificial Intelligence, Medicine, Anti-aging Biotechnology, and Nanotechnology.
Known for identifying cutting edge technologies, he is currently a Co-Founder of a startup and fundraiser for high potential early-stage companies. He is the Head of Research for Allocations for deep technology investments and an Angel Investor at Space Angels.
A frequent speaker at corporations, he has been a TEDx speaker, a Singularity University speaker and guest at numerous interviews for radio and podcasts. He is open to public speaking and advising engagements.