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.

中文翻译：

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长寿海鸟中癌症相关基因的年龄依赖性表达。


对小鼠和大鼠等模型动物的研究使我们对肿瘤发生过程的理解取得了巨大进展，但这一研究领域对理解癌症抵抗机制的贡献甚微。从天然抗癌分子机制的角度增加非模式物种的多样性可以带来对肿瘤过程保护机制进化的新见解，并更广泛地了解天然癌症防御机制。这些知识最终可以用于人类癌症疗法的开发。我们在这里建议，海鸟是有前途的，尽管目前完全被忽视的研究癌症防御机制的候选者，因为它们的最大寿命比根据其体型和能量代谢率预期的要长，因此可能进化出限制肿瘤进展的机制，特别是在年龄较大的时候。我们在这里应用一种新颖的种内方法来比较年老和年轻的海鸟，以提高我们对自然环境中衰老和肿瘤过程的理解。我们根据转录组分析和人类癌症基因直系同源数据库，使用长寿鸥（ Larus canus ）来研究癌症相关基因的年龄相关表达模式。对年轻和年老海鸥之间不同表达的癌症相关基因的分析表明，与人类类似，年龄可能会影响该物种的癌症风险。在各组之间 11 个差异表达的癌症相关基因中，有 3 个可能人为地与癌症相关。与年轻海鸥相比，老海鸥中其余八种基因的表达下调。 其中五个的下调可以解释为抑制肿瘤风险的机制，而三个则可以解释为增加风险的机制。基于这些结果，我们认为老年海鸥在癌症易感性和基因水平上的肿瘤抑制方面都与年轻海鸥不同。