Understanding of NAD+ metabolism provides many critical insights into health and diseases, yet highly sensitive and specific detection of NAD+ metabolism in live cells and in vivo remains difficult. Here, we present ratiometric, highly responsive genetically encoded fluorescent indicators, FiNad, for monitoring NAD+ dynamics in living cells and animals. FiNad sensors cover physiologically relevant NAD+ concentrations and sensitively respond to increases and decreases in NAD+. Utilizing FiNad, we performed a head-to-head comparison study of common NAD+ precursors in various organisms and mapped their biochemical roles in enhancing NAD+ levels. Moreover, we showed that increased NAD+ synthesis controls morphofunctional changes of activated macrophages, and directly imaged NAD+ declines during aging in situ. The broad utility of the FiNad sensors will expand our mechanistic understanding of numerous NAD+-associated physiological and pathological processes and facilitate screening for drug or gene candidates that affect uptake, efflux, and metabolism of this important cofactor.

中文翻译：

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使用遗传编码的荧光传感器照亮活细胞和体内的NAD +代谢。

对NAD +代谢的了解提供了许多有关健康和疾病的重要见解，但是在活细胞和体内对NAD +代谢进行高度灵敏和特异性的检测仍然很困难。在这里，我们介绍了比例，高响应性的遗传编码荧光指示剂FiNad，用于监测活细胞和动物中NAD +的动态。FiNad传感器覆盖生理相关的NAD +浓度，并对NAD +的增加和减少敏感。利用FiNad，我们进行了各种生物中常见NAD +前体的对比研究，并绘制了它们在增强NAD +水平中的生化作用。此外，我们表明增加的NAD +合成控制激活的巨噬细胞的形态功能变化，并直接成像的NAD +在原位老化过程中下降。