Age‐dependent expression of cancer‐related genes in a long‐lived seabird

Abstract

Studies of model animals like mice and rats have led to great advances in our understanding of the process of tumorigenesis, but this line of study has less to offer for understanding the mechanisms of cancer resistance. Increasing the diversity of nonmodel species from the perspective of molecular mechanisms of natural cancer resistance can lead to new insights into the evolution of protective mechanisms against neoplastic processes and to a wider understanding of natural cancer defense mechanisms. Such knowledge could then eventually be harnessed for the development of human cancer therapies. We suggest here that seabirds are promising, albeit currently completely ignored candidates for studying cancer defense mechanisms, as they have a longer maximum life span than expected from their body size and rates of energy metabolism and may have thus evolved mechanisms to limit neoplasia progression, especially at older ages. We here apply a novel, intraspecific approach of comparing old and young seabirds for improving our understanding of aging and neoplastic processes in natural settings. We used the long‐lived common gulls (Larus canus) for studying the age‐related pattern of expression of cancer‐related genes, based on transcriptome analysis and databases of orthologues of human cancer genes. The analysis of differently expressed cancer‐related genes between young and old gulls indicated that similarly to humans, age is potentially affecting cancer risk in this species. Out of eleven differentially expressed cancer‐related genes between the groups, three were likely artifactually linked to cancer. The remaining eight were downregulated in old gulls compared to young ones. The downregulation of five of them could be interpreted as a mechanism suppressing neoplasia risk and three as increasing the risk. Based on these results, we suggest that old gulls differ from young ones both from the aspect of cancer susceptibility and tumor suppression at the genetic level.

Telomeres, the loop tying cancer to organismal life‐histories

“…The increased anthropogenic impacts on our environment is predicted to result in that the synergistic interaction between environmental stressors, parasites, telomere shortening and cancer development will be accelerated in the future (Giraudeau et al, 2018 , 2019 ; Greaves, 2015 ; Meitern et al, 2020 ; Monaghan, 2014 ; Sepp et al, 2019 ). For example, inverse associations have been observed in TL and air pollution (Zhao et al, 2018 ), traffic noise pollution (Dorado‐Correa et al, 2018 ) and chemical pollutants (Angelier et al, 2019 ; Blévin et al, 2016 ; Stauffer et al, 2017 ).…”

“…To test if the assumption is correct, it would be crucial to get accurate estimates of cancer prevalence among for example, long‐lived sea birds. It is interesting to note that a recent study in common gulls reported a complex downregulation of the expression of eight cancer‐related genes with age, a process that might be interpreted as a mechanism suppressing cancer risk for five of the genes but as increasing the risk for the three other genes differently expressed between young and old gulls (Meitern et al, 2020 ). An important note is, when considering telomerase activity in long‐lived species and in association with cancer, that a detectable telomerase activity not necessarily result in telomere elongation as the enzyme has many other functions (e.g., inhibition of apoptosis in immune cells, enhancement of cellular inflammatory responses and maintenance of mitochondrial function, reviewed in Zheng et al, 2019 ).…”

The interface between ecology, evolution, and cancer: More than ever a relevant research direction for both oncologists and ecologists

“…There is thus a need to explore, especially in long‐lived species, the evolution of protective mechanisms against neoplastic processes and natural cancer defense mechanisms in general. Meitern et al (2020, This volume) proposed that seabirds are promising model given their longevity and their habitats that are currently often polluted. This study revealed that old gulls differ from young ones both from the aspect of cancer susceptibility and of tumor suppression at the genetic level.…”