A study published in Nature offers new insights into how bowhead whales – the longest-living mammals on Earth – maintain genome stability over more than two centuries of life. The findings suggest that the whales’ exceptional lifespan and low cancer incidence may stem from enhanced DNA repair mechanisms, rather than from possessing additional tumor-suppressor genes.
The researchers analyzed connective tissue cells from bowhead whales and compared them with those from humans, mice, and cows. Despite their enormous size and long lifespan, bowhead whales are rarely cancer-prone – a contradiction known as Peto’s paradox.
Whale fibroblasts required fewer oncogenic “hits” to undergo malignant transformation compared with human cells, but they displayed far more efficient DNA repair. Specifically, the study found that whale cells had superior ability to repair DNA double-strand breaks through both homologous recombination and non-homologous end joining. These repair pathways are strongly correlated with species longevity.
A central discovery was the role of the cold-inducible RNA-binding protein (CIRBP), which was found to be highly expressed in whale fibroblasts and tissues. CIRBP enhanced DNA repair efficiency in human cells by promoting both major double-strand break repair pathways and reducing chromosomal abnormalities. When CIRBP was overexpressed in fruit flies, it extended lifespan and increased resistance to irradiation.
This suggests that CIRBP contributes to maintaining genomic stability by protecting DNA ends and supporting efficient repair processes. Unlike species that rely heavily on cell death to eliminate damaged cells, bowhead whales appear to favor faithful DNA repair – a strategy that conserves cell populations and may slow aging.
Whale fibroblasts exhibited lower spontaneous and induced mutation rates than those of other mammals when exposed to mutagens such as N-ethyl-N-nitrosourea or gamma radiation. The cells also showed fewer structural variants and faster resolution of DNA damage after exposure to agents that induce double-strand breaks. These findings collectively point to a robust DNA repair system that minimizes the accumulation of genetic damage over time.
The study indicates how DNA repair efficiency can influence disease susceptibility and lifespan. Understanding the molecular mechanisms that preserve genomic integrity in long-lived species may inform human studies on cancer prevention, aging, and genome stability.
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