Teofilović Ana, Vratarić Miloš, Veličković Nataša, Vojnović Milutinović Danijela, Mladenovic Aleksandra, Prvulovic Milica, Djordjevic Ana
Department of Biochemistry, Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia.
Department of Neurobiology, Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia.
Front Nutr. 2022 May 23;9:899255. doi: 10.3389/fnut.2022.899255. eCollection 2022.
Aging is a progressive process that could disturb metabolic homeostasis in the liver ectopic lipid accumulation, oxidative stress, and deterioration of inflammatory response. Although calorie restriction (CR) is recognized as beneficial for life span and health span prolongation, it is still unclear how late-onset CR, characterized by late beginning and short duration, affects age-related processes. The aim of this study was to examine how late-onset CR-induced metabolic adjustments impact lipid status and inflammation in the liver of old rats. The experiments were conducted on aging male Wistar rats fed (AL) or exposed to late-onset CR (60% of AL daily intake) from 21st to 24th month. The results showed that late-onset CR reduces body weight, visceral adipose tissue and liver mass, and triglyceride levels when compared to old animals on AL diet. The ameliorating effects of CR on lipid metabolism include increased activity of AMP-activated protein kinase, suppressed fatty acid synthesis, stimulated β-oxidation, decreased lipotoxicity, and limited triglyceride synthesis and packaging in the liver. Restricted diet regime, however, does not improve expression of antioxidant enzymes, although it leads to progression of age-related inflammation in the liver, partially through lower corticosterone concentration and decreased activation of glucocorticoid receptor. In conclusion, late-onset CR is able to restore age-related imbalance of lipid metabolism in the liver, but has a negative impact on hepatic inflammatory status, implying that the type of diet for older individuals must be balanced and chosen carefully with appropriate duration and start point.
衰老 是一个渐进的过程，可能会扰乱肝脏的代谢稳态，导致异位脂质堆积、氧化应激和炎症反应恶化。尽管热量限制（CR）被认为有利于延长寿命和健康寿命，但以开始时间晚和持续时间短为特征的迟发性CR如何影响与年龄相关的过程仍不清楚。本研究的目的是探讨迟发性CR诱导的代谢调整如何影响老年大鼠肝脏的脂质状态和炎症。实验在21至24月龄的衰老雄性Wistar大鼠上进行，一组喂食正常饮食（AL），另一组从21月龄到24月龄接受迟发性CR（每日摄入量为AL的60%）。结果表明，与喂食AL饮食的老年动物相比，迟发性CR可降低体重、内脏脂肪组织和肝脏质量以及甘油三酯水平。CR对脂质代谢的改善作用包括增加AMP激活的蛋白激酶活性、抑制脂肪酸合成、刺激β氧化、降低脂毒性以及限制肝脏中甘油三酯的合成和包装。然而，限制饮食方案虽然部分通过降低皮质酮浓度和减少糖皮质激素受体的激活导致肝脏中与年龄相关的炎症进展，但并未改善抗氧化酶的表达。总之，迟发性CR能够恢复肝脏中与年龄相关的脂质代谢失衡，但对肝脏炎症状态有负面影响，这意味着老年人的饮食类型必须平衡，并在适当的持续时间和起始点进行谨慎选择。
