Understanding DNA repair and cancer resistance genes from Bowhead whales to enable 200 year lives in humans

Scientists at the University of Liverpool have sequenced the genome of the bowhead whale, estimated to live for more than 200 years with low incidence of disease.

The bowhead whale is the longest living mammal on earth. The team wanted to understand why they live so long and don’t succumb to some of the same illnesses as humans do earlier in life.

Sequencing of the bowhead whale showed changes in genetic information that related to cell division, DNA repair, disease and aging that with further analysis, could help inform future studies in longevity and cancer resistance.

In their findings published in the journal Cell Reports, the team found as many as 80 candidate genes that may help protect the whale from cancer or contribute to it being the longest living mammal on earth. The team found that the whales have genes related to DNA repair, as well as those regulating how cells proliferate, that differ from those found in humans.

“We know DNA damage and DNA mutation are important for cancer. So when we find genes related to DNA repair and DNA damage responses, we think maybe this could be involved in longevity and disease resistance of the bowhead,” Magalheas said. “In that sense, you don’t find a fountain of youth in the genome but you find some promising leads.”

Longevity work on Bowhead Whales was funded by SENS related organizations

Two groups which funded most of the whale research — the Life Extension Foundation and the Methuselah Foundation — are seeking that magic potion. Life Extension focuses on such things as hormonal and nutritional supplements to fight aging while Methuselah is heavily invested in tissue engineering and regenerative medicine “to create a world where 90 year olds can be as health as 50 year olds, by 2030.”

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Cell Reports – Insights into the evolution of longevity from the bowhead whale genome

Insights into the Evolution of Longevity from the Bowhead Whale Genome (12 pages)

Methuselah’s co-founder and CEO Dave Gobel said it invested in the whale research as part of its “hypothesis that the best way to find out how to become longevity outliers is to study those who already are genetic outliers within mammalian species” and then find “what genetic complexes, pathways seem most common among these outliers and to explore what they do, how they act, and what if any advantages can be derived from them to apply in humans.”

While the whale study offers some hope, Magalheas was quick to point out that it will be years before they know whether any of these genes will lead to new drugs or treatment for humans. There won’t be any bowhead whale supplements on store shelves anytime soon, he joked.

“The ideal scenario would be to take a gene from the bowhead and put it in mouse and see if that mouse is protected from cancer and see if that mouse lives longer,” he said. “Those are quite expensive experiments. We don’t have money to do it yet but that is something we would like to pursue.”

More likely, Magalheas is hoping to “take human cells and modify the human genes to resemble those of the bowhead and see if that has noticeable changes in DNA repair at the cellular level.”

Aubrey de Grey, the SENS Research Foundation’s chief science officer and one of the leading voices on extending human life, said the “biology of aging badly needs studies like this.”

Highlights
* Genome and two transcriptomes of the bowhead whale, the longest-lived mammal
* Bowhead-specific mutations in genes associated with cancer and aging (e.g., ERCC1)
* Duplications in genes associated with DNA repair, cell cycle, and aging (e.g., PCNA)
* Changes in genes related to thermoregulation (UCP1) and other bowhead traits

SOURCES – Eurekalert, CBS News, Cell Reports Journal