Shavlakadze Tea, Morris Melody, Fang Jian, Wang Sharon X, Zhu Jiang, Zhou Weihua, Tse Herman W, Mondragon-Gonzalez Ricardo, Roma Guglielmo, Glass David J
Chemical Biology and Therapeutics, Novartis Institutes for Biomedical Research, 181 Massachusetts Avenue, Cambridge, MA 02139, USA.
Respiratory Diseases, Novartis Institutes for Biomedical Research, 181 Massachusetts Avenue, Cambridge, MA 02139, USA.
Cell Rep. 2019 Sep 17;28(12):3263-3273.e3. doi: 10.1016/j.celrep.2019.08.043.
To understand the changes in gene expression that occur as a result of age, which might create a permissive or causal environment for age-related diseases, we produce a multi-time point age-related gene expression signature (AGES) from liver, kidney, skeletal muscle, and hippocampus of rats, comparing 6-, 9-, 12-, 18-, 21-, 24-, and 27-month-old animals. We focus on genes that changed in one direction throughout the lifespan of the animal, either early in life (early logistic changes), at mid-age (mid-logistic), late in life (late-logistic), or linearly, throughout the lifespan of the animal. The pathways perturbed because of chronological age demonstrate organ-specific and more-global effects of aging and point to mechanisms that could potentially be counter-regulated pharmacologically to treat age-associated diseases. A small number of genes are regulated by aging in the same manner in every tissue, suggesting they may be more-universal markers of aging.
为了解因年龄增长而发生的基因表达变化,这些变化可能为与年龄相关的疾病创造一个许可或因果环境,我们从大鼠的肝脏、肾脏、骨骼肌和海马体中生成了一个多时间点的与年龄相关的基因表达特征(AGES),比较了6个月、9个月、12个月、18个月、21个月、24个月和27个月大的动物。我们关注在动物整个生命周期中朝一个方向变化的基因,这些变化要么发生在生命早期(早期逻辑变化)、中年(中期逻辑变化)、生命后期(后期逻辑变化),要么在动物整个生命周期中呈线性变化。由于 chronological age 而受到干扰的通路显示出衰老的器官特异性和更广泛的影响,并指出了可能通过药理学进行反向调节以治疗与年龄相关疾病的机制。少数基因在每个组织中都以相同的方式受到衰老的调节,这表明它们可能是更普遍的衰老标志物。