Concurrent evolution of anti-aging gene duplications and cellular phenotypes in long-lived turtles

Abstract

There are many costs associated with increased body size and longevity in animals, including the accumulation of genotoxic and cytotoxic damage that comes with having more cells and living longer. Yet, some species have overcome these barriers and have evolved remarkably large body sizes and long lifespans, sometimes within a narrow window of evolutionary time. Here, we demonstrate through phylogenetic comparative analysis that multiple turtle lineages, including Galapagos giant tortoises, concurrently evolved large bodies, long lifespans, and reduced cancer risk. We also show through comparative genomic analysis that Galapagos giant tortoises have gene duplications related to longevity and tumor suppression. To examine the molecular basis underlying increased body size and lifespan in turtles, we treated cell lines from multiple species, including Galapagos giant tortoises, with drugs that induce different types of cytotoxic stress. Our results indicate that turtle cells, in general, are resistant to oxidative stress related to aging, while Galapagos giant tortoise cells, specifically, are sensitive to endoplasmic reticulum stress, which may give this species an ability to mitigate the effects of cellular stress associated with increased body size and longevity.

Unraveling the relationship between cancer and life history traits in vertebrates

“…Turtles have lower mutation rates in mitochondrial and nuclear DNA (Lourenço et al, 2013) than mammals and birds, which may be related to the lower incidence of cancer found in these animals overall. In addition, turtles were recently found to have slower rates of aging and potential cellular mechanisms underlying delayed aging and cancer resistance (da Silva et al, 2022; Glaberman et al, 2021; Reinke et al, 2022). Growths and cancers do occur and can be detected in turtles and crocodilians (Garner et al, 2004; Sykes & Trupkiewicz, 2006).…”

“…Turtles have lower germline mutation rates in mitochondrial and nuclear DNA than mammals and birds (Lourenço et al, 2013), which may be related to lower somatic mutation rates and a lower overall incidence of cancer. In addition, turtles were recently found to have slower rates of aging and derived cellular phenotypes that may be associated with delayed aging and cancer resistance (da Silva et al, 2022;Glaberman et al, 2021;Reinke et al, 2022).…”