Cytochrome b₅ reductases (CYB5R) are required for the elongation and desaturation of fatty acids, cholesterol synthesis and mono-oxygenation of cytochrome P450 enzymes, all of which are associated with protection against metabolic disorders. However, the physiological role of CYB5R in the context of metabolism, healthspan and aging remains ill-defined. We generated CYB5R-overexpressing flies (CYB5R-OE) and created a transgenic mouse line overexpressing CYB5R3 (CYB5R3-Tg) in the C57BL/6J background to investigate the function of this class of enzymes as regulators of metabolism and age-associated pathologies. Gender- and/or stage-specific induction of CYB5R, and pharmacological activation of CYB5R with tetrahydroindenoindole extended fly lifespan. Increased expression of CYB5R3 was associated with significant improvements in several metabolic parameters that resulted in modest lifespan extension in mice. Diethylnitrosamine-induced liver carcinogenesis was reduced in CYB5R3-Tg mice. Accumulation of high levels of long-chain polyunsaturated fatty acids, improvement in mitochondrial function, decrease in oxidative damage and inhibition of chronic pro-inflammatory pathways occurred in the transgenic animals. These results indicate that CYB5R represents a new target in the study of genes that regulate lipid metabolism and healthspan.

细胞色素b ₅还原酶 (CYB5R) 是脂肪酸的延长和去饱和、胆固醇合成和细胞色素 P450 酶的单氧合所必需的，所有这些都与防止代谢紊乱有关。然而，CYB5R 在新陈代谢、健康寿命和衰老方面的生理作用仍然不明确。我们生成了过表达 CYB5R 的果蝇 (CYB5R-OE) 并在 C57BL/6J 背景中创建了过表达 CYB5R3 (CYB5R3-Tg) 的转基因小鼠系，以研究这类酶作为代谢和年龄相关病理调节剂的功能。CYB5R 的性别和/或阶段特异性诱导，以及 CYB5R 与四氢茚满多延长苍蝇寿命的药理学激活。CYB5R3 表达增加与一些代谢参数的显着改善相关，从而导致小鼠寿命适度延长。在 CYB5R3-Tg 小鼠中，二乙基亚硝胺诱导的肝癌发生减少。在转基因动物中发生高水平长链多不饱和脂肪酸的积累、线粒体功能的改善、氧化损伤的减少和慢性促炎途径的抑制。这些结果表明，CYB5R 代表了研究调节脂质代谢和健康寿命的基因的新靶点。在转基因动物中发生了氧化损伤的减少和慢性促炎途径的抑制。这些结果表明，CYB5R 代表了研究调节脂质代谢和健康寿命的基因的新靶点。在转基因动物中发生了氧化损伤的减少和慢性促炎途径的抑制。这些结果表明，CYB5R 代表了研究调节脂质代谢和健康寿命的基因的新靶点。