Omega-3 PUFAs Slow Organ Aging through Promoting Energy Metabolism. Omega-3 PUFAs Slow Organ Aging through Promoting Energy Metabolism

Energy metabolism dysfunction is highly connected with aging. Aged mice could exhibit multiple energy metabolism disorders, such as insulin resistance, inhibition of fatty acid degradation and lipid accumulation. PPARα is a key transcriptional factor regulating genes of fatty acid β-oxidation, playing a crucial role in lipid metabolism and ATP production. However, the role of PPARα in retarding organ aging has not been fully elucidated. Herein, we investigated the beneficial effects of Omega-3 PUFAs, endogenous agonists of PPARα, in naturally aging mice, accelerated aging mice as well as several kinds of cells cultures. Moreover, we performed studies in mfat-1 transgenic mice at 24 months of age to explore the anti-aging effects of Omega-3 PUFAs. We found that Omega-3 PUFAs and fat-1 gene restored fatty acid β-oxidation and ATP production, reduced lipid accumulation, inhibited age-related pathological changes, preserved organ functions to delay aging process. Our results suggest Omega-3 PUFAs is a promising therapeutic approach to promote healthy aging in the elderly. Overall design: We performed transcriptomics sequencing analysis of kidney to further the beneficial effects of fat-1 gene in 24-month-old mice.

能量代谢功能紊乱与衰老密切相关。老年小鼠可表现出多种能量代谢紊乱症状，如胰岛素抵抗、脂肪酸降解受抑及脂质蓄积。过氧化物酶体增殖物激活受体α（PPARα）是调控脂肪酸β-氧化相关基因的关键转录因子，在脂质代谢与三磷酸腺苷（ATP）生成过程中发挥关键作用。然而，PPARα在延缓器官衰老中的作用尚未完全阐明。
本研究中，我们针对天然衰老小鼠、加速衰老小鼠及多种细胞培养模型，探究了PPARα的内源性激动剂ω-3多不饱和脂肪酸（Omega-3 PUFAs）的有益效应。此外，我们对24月龄的mfat-1转基因小鼠开展相关实验，以探索Omega-3 PUFAs的抗衰老效果。研究发现，Omega-3 PUFAs与fat-1基因可恢复脂肪酸β-氧化与ATP生成水平，减少脂质蓄积，抑制衰老相关病理变化，维持器官功能以延缓衰老进程。本研究结果表明，Omega-3 PUFAs是一种极具潜力的治疗手段，可用于促进老年人的健康衰老。
整体实验设计：我们对24月龄小鼠的肾脏组织进行转录组测序分析，以进一步验证fat-1基因的有益作用。