Insights into a long life without cancer: The case of the bowhead whale.

Abstract

Long-lived and large-bodied organisms face an inherent challenge: The more cells they contain and the longer they live, the greater the cumulative risk of acquiring mutations that can drive cancer. Yet, paradoxically, cancer incidence does not always scale with size or lifespan-a phenomenon known as Peto's paradox. This observation implies that some species have evolved highly effective anticancer mechanisms that preserve cellular and tissue integrity over long lifespans. Whales, which combine extreme longevity with vast numbers of cells, exemplify this paradox. In this commentary, we discuss a recent study showing that a key contributor to bowhead whales' exceptional lifespan and cancer resistance is their superior genome maintenance capacity. We further discuss DNA repair as a determinant of longevity in other long-lived species and explore how these naturally occurring mechanisms could be harnessed to improve genome integrity, reduce cancer risk, and promote healthy aging in humans.