Laboratory of Molecular Radiobiology and Gerontology, Komi Science Center, Institute of Biology, Ural Branch, Russian Academy of Sciences, 28 Kommunisticheskaya St., Syktyvkar, Komi Republic, Russian Federation, 167982.
Pitirim Sorokin Syktyvkar State University, Syktyvkar, Komi Republic, Russian Federation, 167001.
Biogerontology. 2019 Apr;20(2):159-170. doi: 10.1007/s10522-018-9784-2. Epub 2018 Nov 24.
Diet restriction is one of the most accurately confirmed interventions which extend lifespan. Genes coding circadian core clock elements are known to be the key controllers of cell metabolism especially in aging aspect. The molecular mechanisms standing behind the phenomenon of diet-restriction-mediated life extension are connected to circadian clock either. Here we investigate the effects of protein-rich and low-protein diets on lifespan observed in fruit flies overexpressing core clock genes (cry, per, Clk, cyc and tim). The majority of core clock genes being upregulated in peripheral tissues (muscles and fat body) on protein-rich diet significantly decrease the lifespan of male fruit flies from 5 to 61%. Nevertheless, positive increments of median lifespan were observed in both sexes, males overexpressing cry in fat body lived 20% longer on poor diet. Overexpression of per also on poor medium resulted in life extension in female fruit flies. Diet restriction reduces mortality caused by overexpression of core clock genes. Cox-regression model revealed that diet restriction seriously decreases mortality risks of flies which overexpress core clock genes. The hazard ratios are lower for flies overexpressing clock genes in fat body relatively to muscle-specific overexpression. The present work suggests a phenomenological view of how two peripheral circadian oscillators modify effects of rich and poor diets on lifespan and hazard ratios.
饮食限制是最能准确证实的延长寿命的干预措施之一。已知编码昼夜节律核心生物钟元件的基因是细胞代谢的关键控制器，尤其是在衰老方面。饮食限制介导的寿命延长背后的分子机制也与生物钟有关。在这里，我们研究了在过表达核心生物钟基因（cry、per、Clk、cyc 和 tim）的果蝇中观察到的高蛋白和低蛋白饮食对寿命的影响。大多数核心生物钟基因在高蛋白饮食下在周围组织（肌肉和脂肪体）中上调，这显著缩短了雄性果蝇的寿命，从 5 天缩短至 61 天。然而，在两性中都观察到了中位寿命的显著延长，在脂肪体中过表达 cry 的雄性果蝇寿命延长了 20%。在低蛋白培养基中过表达 per 也导致了雌性果蝇的寿命延长。饮食限制降低了核心生物钟基因过表达导致的死亡率。Cox 回归模型显示，饮食限制严重降低了过表达核心生物钟基因的果蝇的死亡率风险。相对于肌肉特异性过表达，过表达时钟基因的果蝇的危险比更低。本工作提出了一种现象学观点，即两个外周生物钟振荡器如何修饰丰富和贫瘠饮食对寿命和危险比的影响。
