Institute of Healthy Ageing, Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK.
European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
Nat Commun. 2017 May 23;8:15458. doi: 10.1038/ncomms15458.
Ageing generates senescent pathologies, some of which cause death. Interventions that delay or prevent lethal pathologies will extend lifespan. Here we identify life-limiting pathologies in Caenorhabditis elegans with a necropsy analysis of worms that have died of old age. Our results imply the presence of multiple causes of death. Specifically, we identify two classes of corpse: early deaths with a swollen pharynx (which we call 'P deaths'), and later deaths with an atrophied pharynx (termed 'p deaths'). The effects of interventions on lifespan can be broken down into changes in the frequency and/or timing of either form of death. For example, glp-1 mutation only delays p death, while eat-2 mutation reduces P death. Combining pathology and mortality analysis allows mortality profiles to be deconvolved, providing biological meaning to complex survival and mortality profiles.
衰老是导致衰老相关疾病的主要原因,其中一些疾病会导致死亡。延缓或预防致命性疾病的干预措施将延长寿命。在这里,我们通过对因衰老而死亡的线虫进行尸检分析,确定了线虫的寿命限制型疾病。我们的结果表明存在多种死亡原因。具体来说,我们确定了两种类型的尸体:咽肿胀的早期死亡(我们称之为“P 死亡”),以及咽萎缩的后期死亡(称为“p 死亡”)。干预措施对寿命的影响可以分解为这两种死亡形式的频率和/或时间的变化。例如,glp-1 突变仅延迟 p 死亡,而 eat-2 突变减少 P 死亡。将病理学和死亡率分析结合起来,可以对死亡率分布进行解卷积,为复杂的生存和死亡率分布提供生物学意义。