Shijing Lauo/The New York Times

Worm world | Research indicates that disabling the SET-26 gene in worms increases longevity, bringing hope that a similar effect might be seen in humans.

February 13, 2018

Gene in Worms Could Be Key to Longer Human Lifespan

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Popular legend claims that drinking from the fountain of youth will keep one’s body vigorous and vivacious for years to come.
Prof. Sylvia Lee, molecular biology and genetics, may have discovered such an elixir in the soils of Ithaca. Her research indicates the secret of immortality may be hidden in the genome of a worm.

Lee found that Caenorhabditis elegans, a common species of soil worm, has a very similar lifespan and reproductive pattern to humans, importantly sharing hallmark features of human aging. These similarities make C. elegans a premier experimental model to reveal the mysterious mechanisms of mortality in humans.

Although mortality has worried people since the beginning of humankind, scientists do not understand the process of aging very well. We do know that the length of certain structures on the ends of chromosomes called telomeres play a role, as do certain byproducts of human metabolism known as free radicals. Studies have found potentially important genetic factors as well.

For Lee, the most important question is how can humans age in a healthier manner. Wanke Wang grad, a student in Lee’s lab, recently found that two genes in the C. elegans genome, called SET-26 and SET-9, are associated with a longer and healthier life in worms. Initially, Wang and Lee thought both genes influenced aging. They later found that SET-26 was the key gene since it is present in all worm cells, while SET-9 protein only appears in the worm’s reproductive cells.

What was the SET-26 gene doing to influence the aging process in worms? Lee and Wang set out to parse the gene’s role in C. elegans by performing a gene knockout — disabling the SET-26 gene’s function. Lee and Wang observed a three-day addition to the worms’ lifespan, which is normally two to three weeks. More critically, with the SET-26 gene function disrupted, the worms appeared more robust, alert and resilient to stress as they aged.

In a normal cell, DNA is compactly wrapped around molecules called histones. The SET-26 gene codes for a protein that modifies this bundling process. Lee explains that the SET-26 protein recognizes a receptor called Histone H3-Lysine 4, which modulates how securely the DNA is coiled. Lee describes this as a “decoration on the histone which changes how tightly the DNA gets wrapped.”

The SET-26 protein ensures that only the section of DNA adjacent to the receptor gets wrapped. Once deactivated, the absence of the SET-26 protein allows more DNA to come in contact with the receptor region and, somehow, extends the life of the worm. A big mystery remains, however. Lee and Wang know that more DNA bundling leads to longer life in worms, but they do not know why this occurs.

But Lee is hopeful that the increased longevity and resilience in worms with the disabled SET-26 gene could be applied to humans in the future.

“The SET-26 protein itself has a good homolog (functionally similar gene) in humans which is actually not very well studied,” Lee explained.

With more research and a little more time, Lee believes gene therapy that improves the health and vigor of older individuals could become a reality.

Lee said that one of the most exciting aspects of her research is the possibility of intergenerational epigenetic influence on aging. It is possible that an individual could influence the longevity of their progeny by passing down specific histone molecule modifications. These modifications can be preserved through generations and result in entire family lines of healthy agers.

While the project was performed on a molecular level, the future impact and implications of this discovery may be massive. With a healthier senior population, individuals can work longer, retire later and decrease their reliance on social safety nets such as social security, all while also staving off the gray hairs and senility.