Delta Opioid Peptide [d-Ala2, d-Leu5]-Enkephalin Improves Physical and Cognitive Function and Increases Lifespan in Aged Female Mice.

Autor: Huo L; Huzhou Key Laboratory of Translational Medicine, The First Affiliated Hospital of Huzhou University, The First People's Hospital of Huzhou, Huzhou, 313000, Zhejiang Province, China., Zhang H; Huzhou Key Laboratory of Translational Medicine, The First Affiliated Hospital of Huzhou University, The First People's Hospital of Huzhou, Huzhou, 313000, Zhejiang Province, China., Tang C; Huzhou Key Laboratory of Translational Medicine, The First Affiliated Hospital of Huzhou University, The First People's Hospital of Huzhou, Huzhou, 313000, Zhejiang Province, China., Cui G; Department of Pathology, The First Affiliated Hospital of Huzhou University, The First People's Hospital of Huzhou, Huzhou, 313000, Zhejiang Province, China., Xue T; Clinical Research Center, The First Affiliated Hospital of Huzhou University, The First People's Hospital of Huzhou, Huzhou, 313000, Zhejiang Province, China., Guo H; Huzhou Key Laboratory of Translational Medicine, The First Affiliated Hospital of Huzhou University, The First People's Hospital of Huzhou, Huzhou, 313000, Zhejiang Province, China., Yao F; Huzhou University, Huzhou, 313000, Zhejiang Province, China.; Department of Hepatobiliary Pancreatic Surgery, The First Affiliated Hospital of Huzhou University, The First People's Hospital of Huzhou, No. 158, Guangchanghou Road, Wuxing District, Huzhou, 313000, Zhejiang Province, China., Zhang W; Huzhou Key Laboratory of Translational Medicine, The First Affiliated Hospital of Huzhou University, The First People's Hospital of Huzhou, Huzhou, 313000, Zhejiang Province, China., Feng W; Department of Hepatobiliary Pancreatic Surgery, The First Affiliated Hospital of Huzhou University, The First People's Hospital of Huzhou, No. 158, Guangchanghou Road, Wuxing District, Huzhou, 313000, Zhejiang Province, China. fengwenming_wm@126.com.
Jazyk: angličtina
Zdroj: Molecular neurobiology [Mol Neurobiol] 2024 Sep 23. Date of Electronic Publication: 2024 Sep 23.
DOI: 10.1007/s12035-024-04503-y
Abstrakt: In this study, we explored the potential application of [d-Ala2, d-Leu5]-enkephalin (DADLE) in anti-ageing field in response to the trend of increasing global population ageing. We aimed to reveal experimentally whether DADLE can positively affect the lifespan and health of aged mammals through its unique anti-inflammatory or metabolic mechanisms. Forty-two female C57/BL6J mice aged 18 months were intraperitoneally injected with DADLE or normal saline for 2 months. Cognitive and motor functions were assessed using a water maze and treadmill stress test, respectively. The expressions of P16INK4A, Lamin B1 and sirtuin 1 were observed in the hippocampus and heart. The level of pro-inflammatory cytokines in the serum was measured by enzyme-linked immunosorbent assay. The telomere length of the mice was determined using the polymerase chain reaction method. Transcriptome analysis of 6-month-old female C57BL/6 J mice brains and hearts was assessed for body weight effects. Supplementation of exogenous DADLE to aged mice has demonstrated significant benefits, including improved motor function, enhanced cognitive performance and significantly extended lifespan. DADLE treatment resulted in a substantial increase in anti-ageing markers and a corresponding decrease in pro-ageing markers in the heart and brain of these mice. DADLE attenuated age-related inflammation, as evidenced by reductions in serum pro-inflammatory cytokines and inflammatory cell infiltration in tissues. Furthermore, DADLE supplementation significantly prolonged relative telomere length in aged female mice, suggesting a potential mechanism for its anti-ageing effects. Transcriptome analysis revealed that immune response and cellular signalling pathways are intricately involved in the protective effects of DADLE in aged mice, providing further insights into its mechanism of action. Inflammatory reaction may be improved by DADLE by regulating the infiltration of inflammatory cells in the liver and kidney and regulating the cognitive function of the brain and the ageing of the heart in mice.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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