Natural Health

Tweak Just One Gene to Double Lifespan?

Tweak Just One Gene to Double Lifespan? about undefined
1993 was the year Cynthia Kenyon's lab made an historic breakthrough.

By partially disabling a gene called daf-2, her team able to double the lifespan of worms, the largest extension of life in any organism at the time. On top of that, the worms were completely healthy until the end of their lives.

The finding shocked the scientific community because it demonstrated what they thought impossible -- that aging can be controlled. I remember the discovery well because, at least in my mind, it inaugurated the modern age of life extension.

Before that it was all talk about supplements, diet and exercise – the usual lifestyle advice. Not potent medical interventions.

Dr. Kenyon is confident the technique will work in humans.

Daf-2 Mutant Extends Human Life

In the tiny roundworms called Caenorhabditis elegans that the molecular biologist was working with, Daf-2 -- one of worm’s 20,000 genes -- activates receptors that are sensitive to the hormones insulin and insulin growth factor-1 (IGF-1). The Daf-2 gene performs the same function in all species.

Insulin transfers glucose and nutrients into cells, while IGF-1 promotes growth. But Dr Kenyon believes the two hormones have another function, and that is to affect aging.

Other research groups carried out the same experiments in flies and mice and found they, too, lived longer.

There's good reason to believe human lives would also be extended. Not only do we have about the same number of genes as a worm, but a study of Ashkenazi Jews living in New York found those in their 90s and beyond were more likely to have mutations in daf-2.

These winners in the gene lottery were also less likely to get cancer, Alzheimer's, heart disease and other diseases of aging.

The Role of FOXO

In a person with the Daf-2 mutation, a second gene is activated called FOXO. This regulator gene then switches on or off a whole host of other genes.

The switched-on genes function as antioxidants, make sure proteins fold and function correctly, repair DNA, promote autophagy – i.e., escorting damaged proteins into the cell's garbage can for disposal or recycling -- and activate the immune system. Many of these different genes have been shown to contribute to the long lifespan of the daf-2 mutant gene itself.

In a person with a normal daf-2 gene, FOXO is unable to turn on these protector genes.

Why would a mechanism exist that only allows a mutation to extend life?

Dr. Kenyon believes that when food is in good supply, insulin and IGF-1 are active and energy can be stored.

But in bad times, when the organism is experiencing food shortage and conditions of stress, the hormones drop and trigger a danger signal that activates FOXO. The effect is to allow the insect or animal to protect and repair itself and ultimately live when otherwise it would die.

All humans have FOXO, and, as with daf-2 mutants, certain forms of this gene are found more frequently in people who live to a ripe old age.

Sugar is The New Tobacco

In her lab at the University of California at San Francisco, Dr. Kenyon has been trying to come up with drugs that will delay aging and age-related diseases by activating FOXO in human cells.

She believes this molecular pathway is the key to extending life. She says, "I'm really optimistic, and I think it won't be too long, I hope, before this age-old dream begins to come true."

While we're waiting for Dr. Kenyon to come up with a breakthrough drug, there's something we can all do to help prevent premature aging, as she explained in an interview.

"We gave our worms a tiny bit of sugar and it shortened their lifespan by revving up the insulin pathway. I didn't go home," she laughs, "I went straight to the store and I bought a book on low-GI [glycemic index] diets and found a recipe and that was it, I changed immediately."

Apart from dark chocolate, Dr Kenyon avoids all sugar, as well as bread, and sticks to foods low on the glycemic index to keep her blood sugar as stable as possible. She calls sugar "the new tobacco."
  1. https://www.theguardian.com/science/2013/mar/17/cynthia-kenyon-rational-heroes-interview
  2. https://www.ncbi.nlm.nih.gov/pubmed/8247153
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526670/
  4. https://www.ted.com/talks/cynthia_kenyon_experiments_that_hint_of_longer_lives?language=en

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