Calorie restriction has many beneficial effects on healthspan and lifespan in a variety of species. However, how late in life application of caloric restriction can extend fly life is not clear. Here we show that late-life calorie restriction increases lifespan in female Drosophila melanogaster aged on a high-calorie diet. This shift results in rapid decrease in mortality rate and extends fly lifespan. In contrast, shifting female flies from a low- to a high-calorie diet leads to a rapid increase in mortality and shorter lifespan. These changes are mediated by immediate metabolic and physiological adaptations. One of such adaptation is rapid adjustment in egg production, with flies directing excess energy towards egg production when shifted to a high diet, or away from reproduction in females shifted to low-caloric diet. However, lifelong female fecundity reveals no associated fitness cost due to CR when flies are shifted to a high-calorie diet. In view of high conservation of the beneficial effects of CR on physiology and lifespan in a wide variety of organisms, including humans, our findings could provide valuable insight into CR applications that could provide health benefits later in life.

热量限制对多种物种的健康和寿命有许多有益的影响。然而，在生命后期应用热量限制如何能够延长果蝇的寿命尚不清楚。在这里，我们表明，晚年热量限制可以延长高热量饮食的雌性黑腹果蝇的寿命。这种转变导致死亡率迅速下降并延长果蝇寿命。相比之下，将雌性果蝇从低热量饮食转向高热量饮食会导致死亡率迅速增加和寿命缩短。这些变化是由即时代谢和生理适应介导的。其中一种适应是产蛋量的快速调整，果蝇在转向高饮食时将多余的能量用于产蛋，或者在雌性转向低热量饮食时将多余的能量用于产蛋。然而，当果蝇转向高热量饮食时，终生雌性繁殖力表明，CR 不会导致相关的健康成本。鉴于 CR 对包括人类在内的多种生物体的生理和寿命的有益影响高度保守，我们的研究结果可以为 CR 应用提供有价值的见解，从而为以后的生活带来健康益处。