The super surprise here is that a combination of gene
therapies both effective and extending life triggered a huge life extension by
somehow reinforcing each other unexpectedly.
Imagine just how easy this was to miss.
Now we will search forever.
As posted before, life extension research is just getting
going. The payoff is huge. Just allowing everyone to work productively
until the age of 100 in good health will eliminate the bulk of our health care
budgets. Then we add in the effective
doubling of human output that such a lifespan supports.
The cost benefit equation will be hugely shifted and a
hugely enriched civilization will naturally follow.
Five-Fold Lifespan Extension in C. Elegans by Combining
Mutants
Research Highlights Possibility of Combination
Therapy for Aging
December
12, 2013/Novato, California: What are the limits to longevity? New
research in simple animals suggests that combining mutants can lead to
radical lifespan extension. Scientists at the Buck Institute combined
mutations in two pathways well-known for lifespan extension and report a
synergistic five-fold extension of longevity in the nematode C. elegans. The research, done at the
Buck Institute and published online in Cell Reportson December 12, 2013, introduces the possibility
of combination therapy for aging and the maladies associated with it.
The
mutations inhibited key molecules involved in insulin signaling (IIS) and the
nutrient signaling pathway Target of Rapamycin (TOR). Lead scientist and Buck
faculty Pankaj Kapahi, PhD, said single mutations in TOR (in this case RSKS-1)
usually result in a 30 percent lifespan extension, while mutations in IIS
(Daf-2) often result in a doubling of lifespan in the worms – added together
they would be expected to extend longevity by 130 percent. “Instead,
what we have here is a synergistic five-fold increase in lifespan,” Kapahi
said. “The two mutations set off a positive feedback loop in specific tissues
that amplified lifespan. Basically these worms lived to the human
equivalent of 400 to 500 years.”
[ it came down to engineering a virtuous
feedback loop – arclein ]
Kapahi
said the research points to the possibility of using combination therapies for
aging, similar to what is done for cancer and HIV. “In the early years, cancer
researchers focused on mutations in single genes, but then it became apparent
that different mutations in a class of genes were driving the disease process,”
he said. “The same thing is likely happening in aging.” Kapahi said this
research could help explain why scientists are having a difficult time
identifying single genes responsible for the long lives experienced by human
centenarians. “It’s quite probable that interactions between genes are critical
in those fortunate enough to live very long, healthy lives.”
Former
Buck postdoctoral fellow Di Chen, PhD, now an associate professor at the Model
Animal Research Center, Nanjing University, China, lead author of the study,
said that the positive feedback loop (DAF-16 via the AMPK complex) originated
in the germline tissue of worms. The germline is a sequence of reproductive
cells that may be passed onto successive generations. “The germline was the key
tissue for the synergistic gain in longevity – we think it may be where the
interactions between the two mutations are integrated,” Chen said. “The finding
has implications for similar synergy between the two pathways in more complex
organisms.”
Kapahi
said ideally the research would move into mice as a way of determining if the
lifespan-extending synergy extends into mammals. “The idea would be to use mice
genetically engineered to have suppressed insulin signaling, and then treat
them with the drug rapamycin, which is well-known to suppress the TOR pathway.”
Other
Buck Institute researchers involved in the study include Patrick Wai-Lun Li,
Emma Lynn Thomas, and Simon Melov. Other contributors include Benjamin A.
Goldstein and Alan Hubbard from the School of Public Health, University of
California, Berkeley and Waijiao Cai, from the Institute of Traditional Chinese
and Western Medicine, Huashan Hospital, Fudan University, Shanghai. The work
was supported by the National Institutes of Health (P30AG025708)( RO1AG038688),
(RL1AAG032113) and (3RL1AG032113-03S1); the American Federation for Aging
Research and the Hillblom Foundation.
Citation: “Germline
Signaling Mediates the Synergistically Prolonged Longevity by Double Mutations
in daf-2 and rsks-1 in C. elegans”;
publishing online December 12, 2013 in Cell Reports.
About
the Buck Institute for Research on Aging
The
Buck Institute is the U.S.’s first independent research organization devoted to
Geroscience – focused on the connection between normal aging and chronic
disease. Based in Novato, CA, The Buck is dedicated to extending “Healthspan”,
the healthy years of human life and does so utilizing a unique
interdisciplinary approach involving laboratories studying the mechanisms of
aging and those focused on specific diseases. Buck scientists strive to
discover new ways of detecting, preventing and treating age-related diseases
such as Alzheimer’s and Parkinson’s, cancer, cardiovascular disease, macular
degeneration, osteoporosis, diabetes and stroke. In their collaborative
research, they are supported by the most recent developments in genomics,
proteomics, bioinformatics and stem cell technologies. For more
information: www.thebuck.org.
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