College of Pharmacy, Dalian Medical University, Dalian, Liaoning Province, China; The First People's Hospital of Foshan, Foshan, Guangdong province, China.
College of Pharmacy, Dalian Medical University, Dalian, Liaoning Province, China; National-Local Joint Engineering Research Center for Drug-Research and Development (R & D) of Neurodegenerative Diseases, Dalian Medical University, Dalian, Liaoning Province, China.
Eur J Pharmacol. 2024 Nov 15;983:176959. doi: 10.1016/j.ejphar.2024.176959. Epub 2024 Aug 30.
Aging is an inevitable law of the process of life during which many physiological functions change. Brain aging is an important mechanism in the occurrence and development of degenerative diseases of the central nervous system. β-Hydroxybutyrate (BHBA) is a water-soluble, endogenous small-molecule ketone that can cross the blood-brain barrier and induce neuroprotective effects. This study aimed to investigate the effects of BHBA on D-galactose (D-gal) induced aging in mice and its underlying mechanisms using in vitro and in vivo experiments. These results indicated that D-gal-induced senescence, oxidative stress, and inflammatory responses were inhibited by BHBA, and autophagy was promoted by BHBA. Mechanistically, we explored the role of metastasis-associated antigen-1 (MTA1) in D-gal-induced damaged in HT22 cells using small interfering RNA (siRNA). The results demonstrated that the expression of MTA1 was significantly increased by BHBA, which attenuated D-gal-induced aging, oxidative stress, and inflammatory responses, and promoted autophagy through the upregulation of MTA1. In conclusion, MTA1 may be a novel target for treating aging caused by neurological damage. BHBA improves brain aging by activating the MTA1 pathway.
衰老是生命过程中不可避免的规律，在此过程中，许多生理功能发生变化。大脑衰老（brain aging）是中枢神经系统退行性疾病发生和发展的重要机制。β-羟丁酸（β-hydroxybutyrate，BHBA）是一种水溶性、内源性小分子酮，可以穿过血脑屏障，发挥神经保护作用。本研究旨在通过体外和体内实验，探讨 BHBA 对 D-半乳糖（D-gal）诱导的小鼠衰老及其潜在机制的影响。这些结果表明，BHBA 抑制了 D-gal 诱导的衰老、氧化应激和炎症反应，并促进了自噬。在机制上，我们使用小干扰 RNA（siRNA）探索了转移相关抗原-1（metastasis-associated antigen-1，MTA1）在 D-gal 诱导的 HT22 细胞损伤中的作用。结果表明，BHBA 显著上调了 MTA1 的表达，通过上调 MTA1 减轻了 D-gal 诱导的衰老、氧化应激和炎症反应，促进了自噬。综上所述，MTA1 可能是治疗神经损伤引起的衰老的一个新靶点。BHBA 通过激活 MTA1 通路改善大脑衰老。
