PDF(Pubmed)
Abstract：
The Peto\'s paradox consists in the observation that individuals from long-lived and large animal species do not experience a higher cancer incidence, despite being exposed for longer time to the possibility of accumulating mutations and having more target cells exposed to the phenomenon. The existence of this paradox has been recently confirmed (Vincze et al., 2022). Concurrently, robust evidence has been published that longevity involves a convergent evolution of cellular mechanisms that prevent the accumulation of mutations (Cagan et al., 2022). It remains unclear which cellular mechanisms are critical to allow the evolution of a large body mass while keeping cancer at bay.
Adding to existing data linking cellular replicative potential and species body mass (Lorenzini et al., 2005), we have grown a total of 84 skin fibroblast cell strains from 40 donors of 17 mammalian species and analyzed their Hayflick\'s limit, i.e., their senescent plateau, and eventual spontaneous immortalization escape. The correlation of immortalization and replicative capacity of the species with their longevity, body mass and metabolism has been assessed through phylogenetic multiple linear regression (MLR).
The immortalization probability is negatively related to species body mass. The new evaluation and additional data about replicative potential strengthen our previous observation, confirming that stable and extended proliferation is strongly correlated with the evolution of a large body mass rather than lifespan.
The relation between immortalization and body mass suggests a need to evolve stringent mechanisms that control genetic stability during the evolution of a large body mass.
Adding to existing data linking cellular replicative potential and species body mass (Lorenzini et al., 2005), we have grown a total of 84 skin fibroblast cell strains from 40 donors of 17 mammalian species and analyzed their Hayflick\'s limit, i.e., their senescent plateau, and eventual spontaneous immortalization escape. The correlation of immortalization and replicative capacity of the species with their longevity, body mass and metabolism has been assessed through phylogenetic multiple linear regression (MLR).
The immortalization probability is negatively related to species body mass. The new evaluation and additional data about replicative potential strengthen our previous observation, confirming that stable and extended proliferation is strongly correlated with the evolution of a large body mass rather than lifespan.
The relation between immortalization and body mass suggests a need to evolve stringent mechanisms that control genetic stability during the evolution of a large body mass.
摘要：
背景：Peto的悖论在于观察到来自长寿和大型动物物种的个体没有经历更高的癌症发病率，尽管暴露于积累突变的可能性的时间更长，并且有更多的靶细胞暴露于这种现象。这一悖论的存在最近得到了证实(Vincze等人。,2022年）。同时,已经发表了有力的证据，表明长寿涉及阻止突变积累的细胞机制的趋同进化（Cagan等.2022年）。目前尚不清楚哪些细胞机制对于允许大体重的进化同时阻止癌症至关重要。
方法：将现有数据与细胞复制潜力和物种体重联系起来（Lorenzini等人。2005),我们已经从17种哺乳动物的40个供体中培养了总共84个皮肤成纤维细胞菌株，并分析了它们的Hayflick极限，即，他们衰老的高原，最终自发的永生化逃脱。物种的永生化和复制能力与其寿命的相关性，体重和代谢已通过系统发育多元线性回归进行评估。
结果：永生化概率与物种体重呈负相关。关于复制潜力的新评估和额外数据加强了我们之前的观察，证实稳定和延长的增殖与大体重的进化密切相关，而不是寿命。
结论：永生化和体质量之间的关系表明，在大体重进化过程中，需要进化出控制遗传稳定性的严格机制。
方法：将现有数据与细胞复制潜力和物种体重联系起来（Lorenzini等人。2005),我们已经从17种哺乳动物的40个供体中培养了总共84个皮肤成纤维细胞菌株，并分析了它们的Hayflick极限，即，他们衰老的高原，最终自发的永生化逃脱。物种的永生化和复制能力与其寿命的相关性，体重和代谢已通过系统发育多元线性回归进行评估。
结果：永生化概率与物种体重呈负相关。关于复制潜力的新评估和额外数据加强了我们之前的观察，证实稳定和延长的增殖与大体重的进化密切相关，而不是寿命。
结论：永生化和体质量之间的关系表明，在大体重进化过程中，需要进化出控制遗传稳定性的严格机制。
