Zhang Hong-Jia, Lan Hai-Quan, Wang Meng-Ying, Wang Cai-Feng, Wei Lu-Gang, Xu Chen
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China.
State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Nanjing Tech University, Nanjing 210009, China.
Metabolites. 2024 Dec 19;14(12):716. doi: 10.3390/metabo14120716.
Aging and age-related diseases are closely linked to an imbalance in energy supply and demand, a condition that can potentially be mitigated through various interventions, including the use of naturally occurring molecules. Norathyriol (NL), a tetrahydroxyxanthone compound, is prevalent in mango fruit and medicinal plants. While studies have indicated that NL may influence metabolism, its effects on aging have not been extensively explored.
We conducted lifespan analysis and measured lipofuscin accumulation in model to evaluate the effects of NL on aging. Additionally, we identified differentially expressed genes (DEGs) through comprehensive RNA-sequencing (RNA-seq) analysis and performed gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGGs) pathway analyses to elucidate the molecular mechanisms underlying NL's effects.
Our study demonstrated that NL at 50 μM extends the lifespan by 15.9% and reduces lipofuscin accumulation in without impacting their feeding capabilities. A total of 928 DEGs were identified in NL-treated worms. The analysis of DEGs indicated that NL's longevity-promoting effects might be due to its regulation of gene expression in lipid metabolism and immune response pathways. Furthermore, the insulin/insulin-like growth factor (IGF)-1 and target of rapamycin (TOR) signaling pathways were implicated in the lifespan-extending effect of NL.
These findings broaden the bioactivity profile of polyphenols and highlight the need for further investigation into the therapeutic potential of NL in combating age-related diseases.
衰老及与年龄相关的疾病与能量供需失衡密切相关，这种情况有可能通过包括使用天然存在的分子在内的各种干预措施得到缓解。诺拉蒂醇（NL）是一种四羟基呫吨酮化合物，在芒果果实和药用植物中普遍存在。虽然研究表明NL可能影响新陈代谢，但其对衰老的影响尚未得到广泛探索。
我们进行了寿命分析，并在模型中测量脂褐素积累，以评估NL对衰老的影响。此外，我们通过全面的RNA测序（RNA-seq）分析鉴定差异表达基因（DEG），并进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析，以阐明NL作用的分子机制。
我们的研究表明，50μM的NL可使寿命延长15.9%，并减少模型中的脂褐素积累，且不影响其进食能力。在经NL处理的线虫中总共鉴定出928个DEG。对DEG的分析表明，NL的促长寿作用可能归因于其对脂质代谢和免疫反应通路中基因表达的调控。此外，胰岛素/胰岛素样生长因子（IGF）-1和雷帕霉素靶蛋白（TOR）信号通路与NL的寿命延长作用有关。
这些发现拓宽了多酚的生物活性谱，并突出了进一步研究NL在对抗与年龄相关疾病方面治疗潜力的必要性。
