Semi-starvation triggers an increase in the protein produced by the PHA-4/Foxa gene, marked in pink, and increases the lifespan of the worm Caenorhabditis elegans.
Credit: Siler Panowski
MELBOURNE: A new gene that may be the key to prolonging both the longevity and the quality of life has been discovered.
"Live long and prosper", say the Vulcans, and "I wish you long life", goes the salutation at a Jewish funeral. Longer life has been a coveted goal in virtually all cultures - fictional or real.
Though aging was once thought to be an inevitable wear and tear process, it turns out science has shown three fool-proof ways to extend the lifespan. None of them are appealing: starve yourself; mess with your insulin hormones; or get rid of your sex cells.
Now, a study published today in the U.K. journal Nature suggests it might be possible to tweak the system with a little more finesse – suggesting we may be able to reap the benefits of longevity without having to pay the costs.
Starvation response
While studying the effects of dietary restriction on the tiny worm Caenorhabditis elegans, Andrew Dillin and his team at the Salk Institute in La Jolla, California, identified a 'starvation response' gene known as PHA-4/Foxa.
When worms are starved this gene springs into action, switching the worm's metabolism over to a longer lifespan 'setting'. Like the conductor of a biological symphony, the starvation gene conducts a whole orchestra of longevity genes whose members produce enzymes that mop up damaging free radicals.
"[PHA-4/Foxa] is the first unique gene in the dietary restriction pathway to be identified," said Dillin. And he believes this raises exciting new opportunities to intervene in lifespan extension. Rather than messing with insulin hormone levels, or semi-starvation, it might be possible to design a drug that would just tweak the PHA-4/Foxa equivalent in mammals, he said.
While no-one can yet say whether the worm gene will have the same effect in mammals, there are reasons to be hopeful. Most dramatically the worm starvation gene does have close mammalian relatives. Known as Foxa genes, they play a key role in starvation by controlling the release of the hormone glucagon, which reset an animal's metabolism so it has a better chance of survival.
Longevity genetics
In fact, much of what is true for worms ends up being true for mammals. For instance: the first evidence that it might be possible to alter lifespan by interfering with genes came from studies of C.elegans by biologist Cynthia Kenyon at the University of California, San Francisco (UCSF), in 1993. She found that tampering with a single gene made worms live twice as long.
Researchers then went on to find a similar effect with an equivalent gene in rats. A recent study has even hinted that same gene is altered in long-lived Jewish Ashkenazi Centenarians.
Malene Hansen is a senior researcher in Kenyon's lab at UCSF. Though cautious about whether the worm finding will hold true for mammals, she said the find is potentially exciting. "You could hit this molecule [PHA-4/Foxa] and still eat as much as you want," she said, but you'd get the benefits of dietary restriction, such as longer life as well as reduced chance of cancer and diabetes.
However, other researchers are less upbeat. "The most they see is around a 25 per cent increase in lifespan [from activating the PHA-4/Foxa gene]," said David Vaux, of LaTrobe University in Melbourne, who once studied cell death and has now turned to his interest to life-span factors in bees.
"Queen bees and worker bees have a 50 fold difference in lifespan - now that's a robust effect," said Vaux.
With continuing research, we may finally crack the "live long" side of the equation. All we have to do then is ensure the "prosper" bit.
