Ruocco Chiara, Ragni Maurizio, Nisoli Enzo
Center of Study and Research on Obesity, Department of Medical Technologies and Translational Medicine, University of Milan, Milan, Italy.
Front Pharmacol. 2024 Nov 25;15:1512526. doi: 10.3389/fphar.2024.1512526. eCollection 2024.
Dietary restriction (DR) has long been recognized as a powerful intervention for extending lifespan and improving metabolic health across species. In laboratory animals, DR-typically a 30%-40% reduction in caloric intake-delays aging and enhances mitochondrial function, oxidative defense, and anti-inflammatory pathways. In humans, findings from the CALERIE™ trial confirm DR's potential benefits, with a 25% caloric reduction over 2 years resulting in reduced visceral fat, improved cardiometabolic health, and favorable gene expression changes linked to proteostasis, DNA repair, and inflammation. However, recent research in genetically diverse mouse populations reveals that the impact of DR on lifespan is substantially modulated by genetic background, underscoring the importance of individual variability. Additionally, emerging evidence challenges previous assumptions that lower body temperature universally benefits lifespan extension, with data indicating complex relationships between thermoregulation, sex, and longevity. These findings underscore the need for nuanced approaches to DR in both research and potential therapeutic applications, with considerations for genetic and sex-specific factors to maximize healthspan and lifespan outcomes.
长期以来，饮食限制（DR）一直被认为是一种强大的干预措施，可延长物种的寿命并改善新陈代谢健康。在实验动物中，饮食限制通常是将热量摄入减少30%-40%，它可以延缓衰老，并增强线粒体功能、氧化防御和抗炎途径。在人类中，CALERIE™试验的结果证实了饮食限制的潜在益处，在两年内将热量摄入减少25%，可减少内脏脂肪，改善心脏代谢健康，并产生与蛋白质稳态、DNA修复和炎症相关的有利基因表达变化。然而，最近对基因多样化小鼠群体的研究表明，饮食限制对寿命的影响受到遗传背景的显著调节，这凸显了个体差异的重要性。此外，新出现的证据挑战了以前的假设，即体温降低普遍有利于延长寿命，数据表明体温调节、性别和寿命之间存在复杂的关系。这些发现强调，在研究和潜在治疗应用中，需要采用细致入微的饮食限制方法，考虑遗传和性别特异性因素，以最大限度地提高健康寿命和寿命结果。
