Aging is a complex multifactorial process that results in a general functional decline, including cognitive impairment. Caloric restriction (CR) can positively influence the aging processes and delay cognitive decline. There is a rhythmic variation in memory and learning processes throughout the day, indicating the involvement of the circadian clock in the regulation of these processes. Despite growing evidence on the efficacy of CR, it has not yet been fully determined whether starting this strategy at an advanced age is beneficial for improving quality of life and eventually, for protection against age-related diseases. Here, we investigated the effect of late-onset CR on the temporal organization of the molecular clock machinery, molecules related to cognitive processes and epigenetic regulation, in the hippocampus of male old rats maintained under constant darkness conditions. Our results evidenced the existence of a highly coordinated temporal organization of Bmal1, Clock, Bdnf, Trkb, Dnmts, Sirt1, and Pgc-1α in the hippocampus of young adult rats. We observed that aging led to cognitive deficits and loss of circadian oscillations of all the above variables. Interestingly, CR restored circadian rhythmicity in all cases and, in addition, improved the cognitive performance of the old animals. This work would highlight the importance of the circadian clock and its synchronization with feeding signals, as the basis of the beneficial effects of CR. Thus, lifestyle modifications, such as CR, might be a powerful intervention to preserve hippocampal circadian organization and cognitive health during aging.

中文翻译：

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迟发性热量限制可改善认知能力，并恢复雄性老年大鼠海马体中神经营养、时钟和表观遗传因子的昼夜节律模式


衰老是一个复杂的多因素过程，会导致一般功能下降，包括认知障碍。热量限制 （CR） 可以积极影响衰老过程并延缓认知能力下降。全天记忆和学习过程有节奏的变化，表明生物钟参与了这些过程的调节。尽管越来越多的证据表明 CR 的疗效，但尚未完全确定在高龄开始这种策略是否有利于提高生活质量，并最终预防与年龄相关的疾病。在这里，我们研究了晚发性 CR 对在恒定黑暗条件下维持的雄性老鼠海马体中分子钟机制的时间组织的影响，这些分子与认知过程和表观遗传调控有关。我们的结果证明，年轻成年大鼠海马中存在 Bmal1 、 Clock 、 Bdnf 、 Trkb 、 Dnmts 、 Sirt1 和 Pgc-1α 高度协调的时间组织。我们观察到衰老导致上述所有变量的认知缺陷和昼夜节律振荡的丧失。有趣的是，CR 在所有情况下都恢复了昼夜节律，此外，还改善了老年动物的认知能力。这项工作将强调生物钟及其与摄食信号同步的重要性，这是 CR 有益效果的基础。因此，生活方式的改变，例如 CR，可能是在衰老过程中保持海马昼夜节律组织和认知健康的有力干预措施。