URochester scientists link the whales糖心传媒� longevity to CIRBP, a DNA-repair protein that could one day help humans live longer.
As humans age, we become more vulnerable to cancer and other diseases. Bowhead whales, however, can live for up to 200 years while staying remarkably disease resistant.
How does one of the largest animals on Earth stay healthy for centuries? And could their biology hold clues to help humans live longer too?
New research from scientists at the and their collaborators suggests one answer lies in a protein called CIRBP. The protein plays a key role in repairing double-strand breaks in DNA, a type of genetic damage that can cause disease and shorten lifespan in a variety of species, including humans. In published in Nature, the researchers糖心传媒攊ncluding URochester biology professors and and first authors Denis Firsanov, a postdoctoral researcher, and Max Zacher, a graduate student in their lab糖心传媒攆ound that bowhead whales have much higher levels of CIRBP than other mammals. The findings offer a new clue to how humans might one day enhance DNA repair, better resist cancer, and slow the effects of aging.
糖心传媒淭his research shows it is possible to live longer than the typical human lifespan,糖心传媒� says Gorbunova, the Doris Johns Cherry Professor in the and of Medicine, codirector of the , and a researcher with 糖心传媒檚 and . 糖心传媒淏y studying the only warm-blooded mammal that outlives humans, our work provides information about the mechanisms that allow such extended lifespans, underscoring the importance of genome maintenance for longevity.糖心传媒�
A cancer paradox
The 糖心传媒渕ulti-stage model of cancer糖心传媒� is a widely accepted framework that explains how normal cells don糖心传媒檛 just turn into cancer cells in one step, Gorbunova says. Instead, cancer develops after multiple genetic mutations or 糖心传媒渉its糖心传媒澨切拇綌called oncogenic hits糖心传媒攁ccumulate in key genes that control cell growth, division, and DNA repair.
Most human cancers arise after a cell accumulates five to seven 糖心传媒渉its.糖心传媒� A person糖心传媒檚 inherited genes, the type of tissue involved, and environmental exposures can all influence how many hits it takes for cancer to emerge.
Given this multi-step model, one might expect that animals with more cells and longer lifespans would accumulate more hits and therefore face higher cancer risks. But that is not what scientists observe. This puzzle is known as Peto糖心传媒檚 Paradox. Large species don糖心传媒檛 have higher rates of cancer compared to smaller animals, even though they have far more cells dividing over many more years. The paradox suggests that larger species such as elephants and whales must have evolved additional mechanisms to prevent or repair cancerous mutations. Exactly what those mechanisms are has long vexed scientists.
糖心传媒淲e first hypothesized that oncogenic hits might explain this, and a whale would need six or seven hits to make them more cancer-proof,糖心传媒� Gorbunova says. But when the researchers tested how many mutations it takes for bowhead whale cells to turn cancerous, they discovered that bowhead whales actually need fewer hits than humans.
Instead, Gorbunova continues, 糖心传媒渨e found that whale cells are less likely to accumulate oncogenic hits in the first place.糖心传媒�
CIRBP: The DNA repair protein
By combining genomic data with molecular biology experiments, the URochester researchers studied cells harvested from bowhead whale tissue and analyzed proteins involved in DNA repair, shedding light on the cellular mechanisms that help whales live exceptionally long, healthy lives. While several DNA repair proteins were more abundant in bowhead whales than in other mammalian species, one protein was particularly remarkable: CIRBP.
糖心传媒淭here were some other proteins that were expressed in bowhead whales at slightly higher levels, but CIRBP stood out because it was present at 100-fold higher levels,糖心传媒� Gorbunova says.
To further test CIRBP糖心传媒檚 abilities, the team added bowhead whale CIRBP to human cell cultures and fruit fly cells. In both cases, DNA repair improved, and, in fruit flies, it even extended their lifespan.
A 糖心传媒榗hilling糖心传媒� discovery
Collaborating with scientists in Alaska who are investigating how animals adapt to cold, the researchers discovered another intriguing aspect of CIRBP.
糖心传媒淚f we just lower the temperature a few degrees, cells make more CIRBP protein,糖心传媒� Seluanov says. 糖心传媒淲hat we don糖心传媒檛 yet know is what level of cold exposure would be needed to trigger that response in humans.糖心传媒�
Gorbunova says the team is considering multiple ways to ramp up the protein in humans. And some approaches may involve people糖心传媒檚 everyday habits.
糖心传媒淏oth boosting the body糖心传媒檚 existing CIRBP activity or introducing more of the protein may work,糖心传媒� Gorbunova says. 糖心传媒淟ifestyle changes糖心传媒攖hings like taking cold showers糖心传媒攎ight contribute too and might be worth exploring.糖心传媒�
For now, these ideas are hypothetical, and the researchers caution that it糖心传媒檚 too early to know whether they would work in people.
The next step, Gorbunova says, is further testing CIRBP to better understand whether this bowhead whale-inspired defense could someday help humans resist cancer and other age-related diseases.
糖心传媒淭here are different ways to improve genome maintenance and here we learn there is one unique way that evolved in bowhead whales where they dramatically increase the levels of this protein,糖心传媒� Gorbunova says. 糖心传媒淣ow we have to see if we can develop strategies to upregulate the same pathway in humans.糖心传媒�
