PDF(Pubmed)
Abstract：
Organ function declines with age, and large-scale transcriptomic analyses have highlighted differential aging trajectories across tissues. The mechanisms 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 different fat depots and skeletal muscle groups, and most brain regions; 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.
摘要：
器官功能随着年龄的增长而下降,和大规模转录组学分析突出了跨组织的差异衰老轨迹。整个生命周期中共享和器官选择性功能变化的潜在机制，然而,仍然知之甚少。鉴于线粒体在维持组织健康所需的细胞过程中的核心作用，因此，我们对年轻（2.5个月）和老年（20个月）小鼠的33个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揭示：1)在任何一组小鼠中，线粒体活动在不同组织中差异很大,在心中始终如一地看到最高的值，棕色脂肪，和肾脏；2）生物性别是线粒体呼吸的重要但次要因素，它的贡献是组织特异性的，胰腺的主要差异，胃,和白色脂肪组织；3）年龄是影响线粒体活性的主要因素，尤其是在不同的脂肪库和骨骼肌群，和大多数大脑区域；4）年龄影响可以是性别和组织特异性的，在胰腺中看到了一些最大的影响，心,脂肪组织,和骨骼肌；和5）当衰老改变大多数组织中线粒体的功能轨迹时，有些人对年龄引起的变化非常有弹性。总之,我们的数据提供了最全面的线粒体呼吸简编,并阐明了不同组织和器官系统衰老的功能特征.
