Different weapons, same war: lessons on tumor resistance and longevity from emerging animal models

Evolution has shaped remarkably diverse species with distinct life histories, and comparative biology provides a novel lens for deciphering the mechanisms of aging and tumorigenesis across species [1,2].Recent discoveries using non-conventional animal models have revealed both cellautonomous and non-cell-autonomous strategies that counteract the elevated tumor risk associated with extended lifespans.Previous studies have established a positive correlation between lifespan and body size, which is that larger animals tend to live longer, even though having tumors is one of the major causes of death and its incidence significantly increases with age.Larger animals have a higher likelihood of developing tumors because their longer lifespans allow for more cell divisions, as well as a higher number of somatic cells, increasing the chances of accumulating mutations for tumorigenesis.Nevertheless, a recent study found that tumor mortality risk is independent of body mass [3], supporting what was proposed in Peto's paradox [4].How large animals resist the onset of tumors remains an intriguing question.Accumulating evidence suggests that the evolution of replicative cellular senescence(definition) effectively suppress tumorigenesis, compensating for greater body size.Moreover, elephants have evolved an additional anti-tumor mechanism by increasing the copy number of Tp53 [5].Notably, an interesting question arises: some small animals exhibit a extreme longevity compared to their relatives with similar body sizes.Replicative senescence is typically absent in these species.How might these animals have evolved alternative strategies to prevent tumor formation?Some bat species are exceptionally long-lived given their small body size.In a recent study, Athar et al. investigated the anti-tumor mechanisms in several long-lived bat species [6].As expected, bats exhibit telomerase activity.However, the authors found that, unlike other long-lived mammals, bat fibroblasts can be easily transformed with just two oncogenic