Effects of resveratrol on in vitro circadian clock gene expression in young and older human adipose-derived progenitor cells.
Effects of resveratrol on in vitro circadian clock gene expression in young and older human adipose-derived progenitor cells.
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DOI：
10.18632/aging.205292
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发表时间：
2024-01-06
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临床前模型的观察研究表明，昼夜节律功能与年龄相关。我们假设年龄与人体组织中细胞自主生物钟功能的下降有关。因此，我们从先前收集的年轻女性参与者（年龄：23.4±2.1岁）和老年女性参与者（年龄：70.6±5.9岁）腹部皮下储存库的白色脂肪组织活检中培养脂肪祖细胞（APC）。使用体外模型，我们比较了核心时钟组件的节律基因表达谱，作为昼夜节律振荡功能的指标。我们观察到年轻和年长 APC 的核心时钟组件具有一致的昼夜节律。表达分析显示，与年轻人相比，老年 APC 中某些成分（CLOCK、CRY1、NR1D1）的水平有所增加。我们还研究了白藜芦醇（RSV），一种众所周知的长寿效应物，其对节律时钟基因表达谱的影响。我们发现，RSV 导致某些成分（CLOCK 和 CRY）的节律性增加，其他成分（PER2、CRY2）的节律性丧失，并改变了一些节律参数（NR1D1 和 NR1D2），这在年轻和年长的 APC 中是一致的。对体外保留的可检测昼夜节律的观察表明，APC 中细胞自主核心时钟的振荡功能在衰老过程的这一阶段得以保留。 RSV 影响 APC 中的核心时钟基因表达，暗示其通过靶向核心时钟作为长寿治疗剂的潜力。
Observational studies in preclinical models demonstrate age-related declines in circadian functions. We hypothesized that age would be associated with declines in function of cell-autonomous circadian clocks in human tissue. Accordingly, we cultured adipose progenitor cells (APCs) from previously collected white-adipose tissue biopsies from abdominal subcutaneous depots of young (Age: 23.4 ± 2.1 yrs) vs. older female participants (Age: 70.6 ± 5.9 yrs). Using an in vitro model, we compared rhythmic gene expression profiles of core clock components, as an indicator of circadian oscillatory function. We observed consistent circadian rhythmicity of core clock components in young and older-APCs. Expression analysis showed increased levels of some components in older-APCs (CLOCK, CRY1, NR1D1) vs. young. We also investigated resveratrol (RSV), a well-known longevity-enhancing effector, for its effects on rhythmic clock gene expression profiles. We found that RSV resulted in gained rhythmicity of some components (CLOCK and CRY), loss of rhythmicity in others (PER2, CRY2), and altered some rhythmic parameters (NR1D1 and NR1D2), consistent in young and older-APCs. The observation of detectable circadian rhythmicity retained in vitro suggests that the oscillatory function of the cell-autonomous core clock in APCs is preserved at this stage of the aging process. RSV impacts core clock gene expression in APCs, implicating its potential as a therapeutic agent for longevity by targeting the core clock.
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