Sarver Dylan C, Saqib Muzna, Chen Fangluo, Wong G William
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States.
Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, United States.
Elife. 2024 Dec 20;13:RP96926. doi: 10.7554/eLife.96926.
Organ function declines with age, and large-scale transcriptomic analyses have highlighted differential aging trajectories across tissues. The mechanism underlying shared and organ-selective functional changes across the lifespan, however, still remains poorly understood. Given the central role of mitochondria in powering cellular processes needed to maintain tissue health, we therefore undertook a systematic assessment of respiratory activity across 33 different tissues in young (2.5 months) and old (20 months) mice of both sexes. Our high-resolution mitochondrial respiration atlas reveals: (1) within any group of mice, mitochondrial activity varies widely across tissues, with the highest values consistently seen in heart, brown fat, and kidney; (2) biological sex is a significant but minor contributor to mitochondrial respiration, and its contributions are tissue-specific, with major differences seen in the pancreas, stomach, and white adipose tissue; (3) age is a dominant factor affecting mitochondrial activity, especially across most brain regions, different fat depots, skeletal muscle groups, eyes, and different regions of the gastrointestinal tract; (4) age effects can be sex- and tissue-specific, with some of the largest effects seen in pancreas, heart, adipose tissue, and skeletal muscle; and (5) while aging alters the functional trajectories of mitochondria in a majority of tissues, some are remarkably resilient to age-induced changes. Altogether, our data provide the most comprehensive compendium of mitochondrial respiration and illuminate functional signatures of aging across diverse tissues and organ systems.
器官功能随年龄增长而衰退，大规模转录组分析突出了不同组织间衰老轨迹的差异。然而，整个生命周期中共同的和器官选择性功能变化背后的机制仍知之甚少。鉴于线粒体在为维持组织健康所需的细胞过程提供能量方面的核心作用，我们对年轻（2.5个月）和年老（20个月）的雌雄小鼠的33种不同组织的呼吸活动进行了系统评估。我们的高分辨率线粒体呼吸图谱显示：（1）在任何一组小鼠中，线粒体活性在不同组织间差异很大，心脏、棕色脂肪和肾脏中的活性始终最高；（2）生物性别是线粒体呼吸的一个显著但次要的影响因素，其影响具有组织特异性，在胰腺、胃和白色脂肪组织中差异较大；（3）年龄是影响线粒体活性的主要因素，尤其是在大多数脑区、不同的脂肪库、骨骼肌群、眼睛和胃肠道的不同区域；（4）年龄效应可能具有性别和组织特异性，在胰腺、心脏、脂肪组织和骨骼肌中可见一些最大的效应；（5）虽然衰老改变了大多数组织中线粒体的功能轨迹，但有些组织对年龄诱导的变化具有显著的抵抗力。总之，我们的数据提供了最全面的线粒体呼吸纲要，并阐明了不同组织和器官系统中衰老的功能特征。
