Limited cell-autonomous anticancer mechanisms in long-lived bats

Fathima Athar, Zhizhong Zheng, Sebastien Riquier, Max Zacher, J. Yuyang Lu, Yang Zhao, Valentin Volobaev, Dominic Alcock, Alex Galazyuk, Lisa Noelle Cooper, Tony Schountz, Lin-Fa Wang, Emma C. Teeling, Andrei Seluanov () and Vera Gorbunova ()
Additional contact information
Fathima Athar: University of Rochester
Zhizhong Zheng: University of Rochester
Sebastien Riquier: University College Dublin
Max Zacher: University of Rochester
J. Yuyang Lu: University of Rochester
Yang Zhao: University of Rochester
Valentin Volobaev: University of Rochester
Dominic Alcock: University College Dublin
Alex Galazyuk: Northeast Ohio Medical University
Lisa Noelle Cooper: Northeast Ohio Medical University
Tony Schountz: Colorado State University
Lin-Fa Wang: Singapore; SingHealth Duke-NUS Global Health Institute
Emma C. Teeling: University College Dublin
Andrei Seluanov: University of Rochester
Vera Gorbunova: University of Rochester

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Several bat species live >20–40 years, suggesting that they possess efficient anti-aging and anti-cancer defenses. Here we investigate the requirements for malignant transformation in primary fibroblasts from four bat species Myotis lucifugus, Eptesicus fuscus, Eonycteris spelaea, and Artibeus jamaicensis – spanning the bat evolutionary tree and including the longest-lived genera. We show that bat fibroblasts do not undergo replicative senescence, express active telomerase, and show attenuated SIPs with dampened secretory phenotype. Unexpectedly, unlike other long-lived mammals, bat fibroblasts are readily transformed by two oncogenic “hits”: inactivation of p53 or pRb and activation of HRASG12V. Bat fibroblasts exhibit increased TP53 and MDM2 transcripts and elevated p53-dependent apoptosis. M. lucifugus shows a genomic duplication of TP53. We hypothesize that some bat species have evolved enhanced p53 activity as an additional anti-cancer strategy, similar to elephants. Further, the absence of unique cell-autonomous tumor suppressive mechanisms may suggest that in vivo bats may rely on enhanced immunosurveillance.

Date: 2025
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DOI: 10.1038/s41467-025-59403-z

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