衰老细胞的积累会诱导多种衰老表型，p53 肿瘤抑制蛋白调节两种已知的细胞衰老途径之一。然而p53对衰老的调节尚不清楚。例如，一些小鼠的 p53 缺陷已被证明可以挽救过早衰老，而另一些小鼠则在 p53 缺陷时表现出显着的衰老表型。本研究旨在从结构和机制上阐明 p53 在长寿中的作用。通过相对进化评分 (RES) 算法，我们量化了六个分类目中不同平均寿命的生物体中 p53 残基的进化变化水平。其次，我们使用 PEPPI 评估了灵长类和鲈形目生物体中 p53 或 p53 连接蛋白与已知衰老调节蛋白之间相互作用的可能性。我们的 RES 算法发现目内和目之间的比对存在差异，这表明 p53 介导的长寿调节机制可能有所不同。 PEPPI 结果表明，寿命较长的物种可能已经进化到比寿命较短的物种更好地调节细胞衰老的诱导和抑制。通过实验验证，这些预测可以帮助阐明 p53 介导的细胞衰老机制，最终阐明我们对 p53 在多物种背景下与衰老的联系的理解。p53 肿瘤抑制蛋白通过修复 DNA 损伤、调节 DNA 损伤、调节 DNA 损伤，保护我们的基因组免受癌症侵害。细胞死亡和/或将细胞推向永久无法分裂的状态（称为细胞衰老）。在小鼠和人类细胞模型中，衰老细胞的积累会产生各种衰老分子特征，从而将 p53 与衰老过程联系起来。然而，p53 调节衰老的分子机制及其对此调节的结构影响尚不清楚。在这项研究中，我们定量评估了多个分类目生物体 p53 序列的进化差异，以确定平均寿命和序列进化之间是否存在关系。此外，我们使用蛋白质-蛋白质相互作用工具来评估 p53 或 p53 相关蛋白与两种分类目（灵长类和鲈形目）不同寿命生物体中的各种衰老相关蛋白之间相互作用的可能性。阐明 p53 结构差异和与 p53 调节细胞衰老相关的机制蛋白质组网络可以推进针对异常衰老的治疗。

The accumulation of senescent cells induces several aging phenotypes, and the p53 tumor suppressor protein regulates one of the two known cellular senescence pathways. p53's regulation of senescence is however not clear. For example, p53 deficiency in some mice has been shown to rescue premature aging while others display significant aging phenotype when p53-deficient. This study seeks to elucidate, structurally and mechanistically, p53's roles in longevity. Through a relative evolutionary scoring (RES) algorithm, we quantify the level of evolutionary change in the residues of p53 across organisms of varying average lifespans in six taxonomic orders. Secondly, we used PEPPI to assess the likelihood of interaction between p53-or p53-linked proteins-and known senescence-regulating proteins across organisms in the orders Primates and Perciformes. Our RES algorithm found variations in the alignments within and across orders, suggesting that mechanisms of p53-mediated regulation of longevity may vary. PEPPI results suggest that longer-lived species may have evolved to regulate induction and inhibition of cellular senescence better than their shorter-lived counterparts. With experimental verification, these predictions could help elucidate the mechanisms of p53-mediated cellular senescence, ultimately clarifying our understanding of p53's connection to aging in a multiple-species context.The p53 tumor suppressor protein protects our genome from cancers by repairing DNA damage, regulating cell death and/or pushing cells to a state where they become permanently unable to divide (known as cellular senescence). An accumulation of senescent cells produces various molecular features of aging in both mouse and human cellular models-thus linking p53 to the aging process. However, the molecular mechanism by which p53 regulates aging and its structural implications on this regulation are not clear. In this study, we assessed quantitatively the evolutionary differences in p53 sequences of organisms across several taxonomical orders to determine if there is a relationship between average lifespan and sequence evolution. In addition, we used a protein-protein interaction tool to assess the likelihood of interaction between p53, or p53-associated protein, and various senescence-associated proteins across organisms of various lifespans in two taxonomic orders: Primates and Perciformes. An elucidation of p53 structural difference and mechanistic proteomic network linked to p53 regulation of cellular senescence could advance therapeutics targeting abnormal aging.