血液衰老时钟 BAP 量化疾病偏离健康分子衰老轨迹的程度
A blood aging clock defines disease-induced deviation from healthy molecular aging
研究团队整合 23 个队列的 10 753 份全血转录组，用其中 5808 名健康个体构建血液衰老预测器 BAP，定义健康血液分子衰老的参考轨迹。将 BAP 应用于 COVID-19 患者后，经队列基线校正，患者平均转录组年龄加速（AgeAccel）达 9.34 年，且这一偏移在各年龄组均出现，并与干扰素信号、免疫炎症激活、细胞因子与中性粒细胞相关程序、DNA 损伤应答、蛋白稳态应激及细胞质量控制通路受损相关。纵向分析显示 AgeAccel 在急性感染期升高、恢复期下降，提示队列层面存在可能可逆的类衰老分子状态。
来源：Briefings in Bioinformatics · doi.org
Aging shapes disease susceptibility and recovery, yet it remains unclear whether disease-induced molecular perturbations can be quantitatively mapped onto healthy aging trajectories. Here, we integrated 10 753 whole-blood transcriptomic profiles from 23 cohorts and developed a blood aging predictor (BAP) using 5808 healthy individuals to define a reference trajectory of blood molecular aging. Applying BAP to COVID-19 revealed marked transcriptomic age acceleration (AgeAccel), with patients showing an average AgeAccel of 9.34 years after cohort-specific baseline correction. This aging-referenced deviation occurred across age groups and was associated with interferon signaling, immune-inflammatory activation, cytokine and neutrophil-related programs, DNA damage responses, proteostasis stress, and impaired cellular quality-control pathways. Longitudinal analysis showed that AgeAccel increased during acute infection but declined during recovery, indicating a potentially reversible aging-like molecular state at the cohort level rather than irreversible aging. Extension to sepsis, influenza, and major depressive disorder further demonstrated that elevated AgeAccel captures disease-associated molecular burden across distinct pathological contexts. Together, our study redefines transcriptomic AgeAccel as an interpretable measure of disease-induced deviation from healthy molecular homeostasis and provides a quantitative framework for assessing systemic disease burden and recovery dynamics from peripheral blood transcriptomes.