Few studies have systematically analyzed how old aging is. Gaining a more accurate knowledge about the natural history of aging could however have several payoffs. This knowledge could unveil lineages with dated genetic hardware, possibly maladapted to current environmental challenges, and also uncover “phylogenetic modules of aging,” i.e., naturally evolved pathways associated with aging or longevity from a single ancestry, with translational interest for anti-aging therapies. Here, we approximated the natural history of the genetic hardware of aging for five model fungal and animal species. We propose a lower-bound estimate of the phylogenetic age of origination for their protein-encoding gene families and protein–protein interactions. Most aging-associated gene families are hundreds of million years old, older than the other gene families from these genomes. Moreover, we observed a form of punctuated evolution of the aging hardware in all species, as aging-associated families born at specific phylogenetic times accumulate preferentially in genomes. Most protein–protein interactions between aging genes are also old, and old aging-associated proteins showed a reduced potential to contribute to novel interactions associated with aging, suggesting that aging networks are at risk of losing in evolvability over long evolutionary periods. Finally, due to reshuffling events, aging networks presented a very limited phylogenetic structure that challenges the detection of “maladaptive” or “adaptative” phylogenetic modules of aging in present-day genomes.

很少有研究系统地分析衰老的程度。然而，获得有关衰老自然史的更准确的知识可能会带来一些好处。这些知识可以揭示具有过时遗传硬件的谱系，这些谱系可能不适应当前的环境挑战，还可以揭示“衰老的系统发育模块”，即与衰老或长寿相关的自然进化途径，来自单一祖先，具有抗衰老疗法的转化意义。在这里，我们对五种模型真菌和动物物种的衰老遗传硬件的自然历史进行了近似。我们提出了对其蛋白质编码基因家族和蛋白质-蛋白质相互作用的起源系统发育年龄的下限估计。大多数与衰老相关的基因家族都有数亿年的历史，比这些基因组中的其他基因家族更古老。此外，我们观察到所有物种中衰老硬件的间断进化，因为在特定系统发育时间出生的与衰老相关的家族优先在基因组中积累。衰老基因之间的大多数蛋白质-蛋白质相互作用也是古老的，并且古老的衰老相关蛋白质显示出促进与衰老相关的新相互作用的潜力降低，这表明衰老网络在长期进化过程中面临着失去进化性的风险。最后，由于重组事件，衰老网络呈现出非常有限的系统发育结构，这对当今基因组中衰老的“适应不良”或“适应性”系统发育模块的检测提出了挑战。