Aging is a complex process that can be characterized by functional and cognitive decline in an individual. Aging can be assessed based on the functional capacity of vital organs and their intricate interactions with one another. Thus, the nature of aging can be described by focusing on a specific organ and an individual itself. However, to fully understand the complexity of aging, one must investigate not only a single tissue or biological process but also its complex interplay and interdependencies with other biological processes. Here, using RNA-seq, we monitored changes in the transcriptome during aging in four tissues (including brain, blood, skin and liver) in mice at 9 months, 15 months, and 24 months, with a final evaluation at the very old age of 30 months. We identified several genes and processes that were differentially regulated during aging in both tissue-dependent and tissue-independent manners. Most importantly, we found that the electron transport chain (ETC) of mitochondria was similarly affected at the transcriptome level in the four tissues during the aging process. We also identified the liver as the tissue showing the largest variety of differentially expressed genes (DEGs) over time. Lcn2 (Lipocalin-2) was found to be similarly regulated among all tissues, and its effect on longevity and survival was validated using its orthologue in Caenorhabditis elegans. Our study demonstrated that the molecular processes of aging are relatively subtle in their progress, and the aging process of every tissue depends on the tissue’s specialized function and environment. Hence, individual gene or process alone cannot be described as the key of aging in the whole organism.

老化是一个复杂的过程，其特征是个体的功能和认知能力下降。可以根据重要器官的功能能力及其彼此之间复杂的相互作用来评估衰老。因此，衰老的本质可以通过关注特定器官和个体本身来描述。然而，要充分了解衰老的复杂性，不仅必须研究单个组织或生物过程，还必须研究其与其他生物过程的复杂相互作用和相互依赖性。在这里，我们使用 RNA-seq 监测了小鼠 9 个月、15 个月和 24 个月时四种组织（包括大脑、血液、皮肤和肝脏）在衰老过程中转录组的变化，并在非常老的时候进行了最终评估30 个月。我们确定了几种基因和过程，它们在衰老过程中以组织依赖性和组织独立方式受到差异调节。最重要的是，我们发现在衰老过程中，线粒体的电子传递链（ETC）在四种组织的转录组水平上受到类似的影响。我们还将肝脏确定为随时间显示差异表达基因 (DEG) 种类最多的组织。发现 Lcn2 (Lipocalin-2) 在所有组织中受到类似的调节，并且使用其在秀丽隐杆线虫中的直向同源物验证了其对长寿和存活的影响。我们的研究表明，衰老的分子过程在其进程中是相对微妙的，每个组织的衰老过程取决于组织的特殊功能和环境。因此，单独的基因或过程不能被描述为整个生物体衰老的关键。