PDF(Pubmed)
Abstract：
GDF15 (growth differentiation factor 15) is a marker of cellular energetic stress linked to physical-mental illness, aging, and mortality. However, questions remain about its dynamic properties and measurability in human biofluids other than blood. Here, we examine the natural dynamics and psychobiological regulation of plasma and saliva GDF15 in four human studies representing 4,749 samples from 188 individuals. We show that GDF15 protein is detectable in saliva (8% of plasma concentration), likely produced by salivary glands secretory duct cells. Using a brief laboratory socio-evaluative stressor paradigm, we find that psychosocial stress increases plasma (+3.5-5.9%) and saliva GDF15 (+43%) with distinct kinetics, within minutes. Moreover, saliva GDF15 exhibits a robust awakening response, declining by ~40-89% within 30-45 minutes from its peak level at the time of waking up. Clinically, individuals with genetic mitochondrial OxPhos diseases show elevated baseline plasma and saliva GDF15, and post-stress GDF15 levels in both biofluids correlate with multi-system disease severity, exercise intolerance, and the subjective experience of fatigue. Taken together, our data establish that saliva GDF15 is dynamic, sensitive to psychological states, a clinically relevant endocrine marker of mitochondrial diseases. These findings also point to a shared psychobiological pathway integrating metabolic and mental stress.
摘要：
GDF15（生长分化因子15）是与身心疾病相关的细胞能量应激的标志，老化，和死亡率。然而,关于其在血液以外的人体生物流体中的动态特性和可测量性的问题仍然存在。这里,我们在4项人体研究中研究了血浆和唾液GDF15的自然动力学和心理生物学调节,这些研究代表了来自188名个体的4,749个样本.我们发现唾液中可检测到GDF15蛋白（血浆浓度的8％），可能由唾液腺分泌导管细胞产生。血浆和唾液GDF15水平不相关。使用简短的实验室社会评估压力源范式，我们发现，心理应激增加血浆（+3.4-5.3％）和唾液GDF15（+45％）具有不同的动力学，几分钟之内。此外，唾液GDF15表现出强烈的觉醒反应，在30-45分钟内从醒来时的峰值下降了42-92%。临床上,患有遗传性线粒体OxPhos疾病的个体显示基线血浆和唾液GDF15升高，并且两种生物流体中的应激后GDF15水平与多系统疾病严重程度相关，锻炼不容忍，和疲劳的主观体验。一起来看,我们的数据建立了唾液GDF15的动态特性，揭示了它对压力敏感，并作为线粒体疾病的临床相关标志物。这些发现指出了整合代谢和精神压力的共同心理生物学途径。
