Department of Comparative Medicine, University of Washington, Seattle, WA 98195, USA.
Ageing Res Rev. 2010 Jul;9(3):269-72. doi: 10.1016/j.arr.2010.02.004. Epub 2010 Feb 24.
Protein kinase A (PKA) is a multi-unit protein kinase that mediates signal transduction of G-protein-coupled receptors through its activation by adenyl cyclase (AC)-mediated cAMP. The vital importance of PKA signaling to cellular function is reflected in the widespread expression of PKA subunit genes. As one of its many functions, PKA plays a key role in the regulation of metabolism and triglyceride storage. The PKA pathway has become of great interest to the study of aging, since mutations that cause a reduction in PKA signaling have been shown to extend lifespan in yeast, and to both delay the incidence and severity of age-related disease, and to promote leanness and longevity, in mice. There is increasing interest in the potential for the inhibition or redistribution of adiposity to attenuate aging, since obesity is associated with impaired function of most organ systems, and is a strong risk factor for shortened life span. Its association with coronary heart disease, hypertension, type 2 diabetes, cancer, sleep apnea and osteoarthritis is leading to its accession as a major cause of global ill health. Therefore, gene signaling pathways such as PKA that promote adiposity are potential inhibitory targets for aging intervention. Since numerous plant compounds have been found that both prevent adipogenesis and inhibit PKA signaling, a focused investigation into their effects on biological systems and the corresponding molecular mechanisms would be of high relevance to the discovery of novel and non-toxic compounds that promote healthy aging.
蛋白激酶 A（PKA）是一种多亚基蛋白激酶，通过其被腺苷酸环化酶（AC）介导的 cAMP 激活来介导 G 蛋白偶联受体的信号转导。PKA 信号对细胞功能的重要性反映在 PKA 亚基基因的广泛表达上。作为其众多功能之一，PKA 在调节代谢和甘油三酯储存中发挥着关键作用。PKA 途径已成为衰老研究的热点，因为已经证明导致 PKA 信号降低的突变可以延长酵母的寿命，并延迟与年龄相关的疾病的发生和严重程度，并促进小鼠的瘦素和长寿。人们越来越关注抑制或重新分配肥胖以减缓衰老的潜力，因为肥胖与大多数器官系统功能受损有关，并且是缩短寿命的强烈危险因素。肥胖与冠心病、高血压、2 型糖尿病、癌症、睡眠呼吸暂停和骨关节炎有关，这使其成为全球健康不良的主要原因。因此，促进肥胖的 PKA 等基因信号通路是衰老干预的潜在抑制靶点。由于已经发现许多植物化合物既能预防脂肪生成又能抑制 PKA 信号，因此对它们对生物系统的影响及其相应的分子机制进行集中研究将高度有助于发现促进健康衰老的新型无毒化合物。
