Lindborg Carter M, Propert Kathleen J, Pignolo Robert J
Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Mech Ageing Dev. 2015 Mar;146-148:23-7. doi: 10.1016/j.mad.2015.03.004. Epub 2015 Mar 21.
Genes which confer a relative longevity advantage may be regulated at the level of transcription or translation. Alternatively, pro-longevity genes may mediate their effects at the level of protein structure-functional relationships that are beneficially optimized in long-lived species. Longevity associated genes (LAGs) may be operationally defined as genes that confer beneficial effects and are relatively more conserved among long-lived species. Global and local protein sequence alignments of over 10,000 genes across at least 30 mammalian species were examined to identify LAGs. Known LAGs, including growth hormone receptor (GHR), and breast cancer 1, early onset (BRCA1), have strong associations with maximum lifespan by our analysis. Several common categories of protein function were observed among genes ranked with the strongest associations with MLS identified by all regression models. These genes included those that function in the immune system, cell cycle regulation, and DNA damage response. We provide a ranking of genes with the strongest associations with species maximum lifespan (MLS) by several phylogenetic generalized least squares regression models, including adjustment for confounding variables such as body weight and gestation length.
赋予相对长寿优势的基因可能在转录或翻译水平受到调控。或者，长寿基因可能在蛋白质结构 - 功能关系层面发挥作用，而这些关系在长寿物种中得到了有益的优化。与长寿相关的基因（LAGs）在操作上可定义为那些具有有益作用且在长寿物种中相对更保守的基因。我们对至少30种哺乳动物的10000多个基因进行了全局和局部蛋白质序列比对，以识别LAGs。通过我们的分析，已知的LAGs，包括生长激素受体（GHR）和乳腺癌1号基因（BRCA1），与最大寿命有很强的关联。在所有回归模型确定的与最大寿命（MLS）关联最强的基因中，观察到了几种常见的蛋白质功能类别。这些基因包括在免疫系统、细胞周期调控和DNA损伤反应中发挥作用的基因。我们通过几种系统发育广义最小二乘回归模型，给出了与物种最大寿命（MLS）关联最强的基因排名，包括对体重和妊娠期长度等混杂变量的校正。
