|
|
Ghrelin与衰弱的可能机制
|
Abstract:
衰弱是老年人跌倒，失能，应激能力下降，住院时间增加等的重要因素，其与肌少症、认知障碍等老年综合征存在显著关联。胃促生长素(Ghrelin)是一种主要由胃部分泌的激素，在促进食欲及能量代谢，调节免疫系统与循环系统等方面具有重要作用。本文就Ghrelin与衰弱的可能机制及研究进展进行综述。
Frailty is a significant factor contributing to falls, disability, decreased stress resilience, and increased hospitalization duration in the elderly, with notable associations to geriatric syndromes such as sarcopenia and cognitive impairment. Ghrelin, a hormone primarily secreted by the stomach, plays a crucial role in stimulating appetite, energy metabolism, and regulating the immune and circulatory systems. This article reviews the potential mechanisms and research progress of Ghrelin in relation to frailty.
| [1] | Sun, J., Tan, Y., Su, J., Mikhail, H., Pavel, V., Deng, Z., et al. (2023) Role and Molecular Mechanism of Ghrelin in Degenerative Musculoskeletal Disorders. Journal of Cellular and Molecular Medicine, 27, 3681-3691. https://doi.org/10.1111/jcmm.17944 |
| [2] | Anderson, K.C., Hasan, F., Grammer, E.E. and Kranz, S. (2023) Endogenous Ghrelin Levels and Perception of Hunger: A Systematic Review and Meta-Analysis. Advances in Nutrition, 14, 1226-1236. https://doi.org/10.1016/j.advnut.2023.07.011 |
| [3] | Mathur, N., Mehdi, S.F., Anipindi, M., Aziz, M., Khan, S.A., Kondakindi, H., et al. (2021) Ghrelin as an Anti-Sepsis Peptide: Review. Frontiers in Immunology, 11, Article 610363. https://doi.org/10.3389/fimmu.2020.610363 |
| [4] | Gray, S.M., Page, L.C. and Tong, J. (2019) Ghrelin Regulation of Glucose Metabolism. Journal of Neuroendocrinology, 31, e12705. https://doi.org/10.1111/jne.12705 |
| [5] | Deng, Y., Zhang, K., Zhu, J., Hu, X. and Liao, R. (2023) Healthy Aging, Early Screening, and Interventions for Frailty in the Elderly. BioScience Trends, 17, 252-261. https://doi.org/10.5582/bst.2023.01204 |
| [6] | Howlett, S.E., Rutenberg, A.D. and Rockwood, K. (2021) The Degree of Frailty as a Translational Measure of Health in Aging. Nature Aging, 1, 651-665. https://doi.org/10.1038/s43587-021-00099-3 |
| [7] | Boucham, M., Salhi, A., El Hajji, N., Gbenonsi, G.Y., Belyamani, L. and Khalis, M. (2024) Factors Associated with Frailty in Older People: An Umbrella Review. BMC Geriatrics, 24, Article No. 737. https://doi.org/10.1186/s12877-024-05288-4 |
| [8] | Zhang, Y., Zhang, R., Wang, X., Shi, L., Zhu, H. and Liu, J. (2025) Potential Role of Ghrelin in Neuroprotection and Cognitive Function: Implications for Diabetic Cognitive Impairment. PeerJ, 13, e18898. https://doi.org/10.7717/peerj.18898 |
| [9] | López, M. and Nogueiras, R. (2023) Ghrelin. Current Biology, 33, R1133-R1135. https://doi.org/10.1016/j.cub.2023.09.009 |
| [10] | Nagaya, N., Kojima, M., Uematsu, M., Yamagishi, M., Hosoda, H., Oya, H., et al. (2001) Hemodynamic and Hormonal Effects of Human Ghrelin in Healthy Volunteers. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 280, R1483-R1487. https://doi.org/10.1152/ajpregu.2001.280.5.r1483 |
| [11] | Lund, L.H., Hage, C., Pironti, G., Thorvaldsen, T., Ljung-Faxén, U., Zabarovskaja, S., et al. (2023) Acyl Ghrelin Improves Cardiac Function in Heart Failure and Increases Fractional Shortening in Cardiomyocytes without Calcium Mobilization. European Heart Journal, 44, 2009-2025. https://doi.org/10.1093/eurheartj/ehad100 |
| [12] | Hosoda, H. (2022) Effect of Ghrelin on the Cardiovascular System. Biology, 11, Article 1190. https://doi.org/10.3390/biology11081190 |
| [13] | He, C., Song, X., Zhu, Z., Xiao, Y., Chen, J., Yao, H., et al. (2024) Correction: Ghrelin May Protect against Vascular Endothelial Injury in Acute Traumatic Coagulopathy by Mediating the RhoA/ROCK/MLC2 Pathway. Journal of Thrombosis and Thrombolysis, 58, 96. https://doi.org/10.1007/s11239-024-03058-y |
| [14] | Yuan, M., Li, W. and Zhong, P. (2021) Research Progress of Ghrelin on Cardiovascular Disease. Bioscience Reports, 41, BSR20203387. https://doi.org/10.1042/bsr20203387 |
| [15] | McKimpson, W.M., Spiegel, S., Mukhanova, M., Kraakman, M., Du, W., Kitamoto, T., et al. (2024) Calorie Restriction Activates a Gastric Notch-Foxo1 Pathway to Expand Ghrelin Cells. Journal of Cell Biology, 223, e202305093. https://doi.org/10.1083/jcb.202305093 |
| [16] | McKimpson, W.M., Kuo, T., Kitamoto, T., Higuchi, S., Mills, J.C., Haeusler, R.A., et al. (2022) FOXO1 Is Present in Stomach Epithelium and Determines Gastric Cell Distribution. Gastro Hep Advances, 1, 733-745. https://doi.org/10.1016/j.gastha.2022.05.005 |
| [17] | Lee, J.H., Fang, C., Li, X., Wu, C.S., Noh, J.Y., Ye, X., et al. (2021) GHS-R Suppression in Adipose Tissues Protects against Obesity and Insulin Resistance by Regulating Adipose Angiogenesis and Fibrosis. International Journal of Obesity, 45, 1565-1575. https://doi.org/10.1038/s41366-021-00820-7 |
| [18] | Neary, N.M., Small, C.J., Wren, A.M., Lee, J.L., Druce, M.R., Palmieri, C., et al. (2004) Ghrelin Increases Energy Intake in Cancer Patients with Impaired Appetite: Acute, Randomized, Placebo-Controlled Trial. The Journal of Clinical Endocrinology & Metabolism, 89, 2832-2836. https://doi.org/10.1210/jc.2003-031768 |
| [19] | Skoracka, K., Hryhorowicz, S., Schulz, P., Zawada, A., Ratajczak-Pawłowska, A.E., Rychter, A.M., et al. (2025) The Role of Leptin and Ghrelin in the Regulation of Appetite in Obesity. Peptides, 186, Article ID: 171367. https://doi.org/10.1016/j.peptides.2025.171367 |
| [20] | Ginter, G., Ceranowicz, P. and Warzecha, Z. (2021) Protective and Healing Effects of Ghrelin and Risk of Cancer in the Digestive System. International Journal of Molecular Sciences, 22, Article 10571. https://doi.org/10.3390/ijms221910571 |
| [21] | Davis, E.A., Wald, H.S., Suarez, A.N., Zubcevic, J., Liu, C.M., Cortella, A.M., et al. (2020) Ghrelin Signaling Affects Feeding Behavior, Metabolism, and Memory through the Vagus Nerve. Current Biology, 30, 4510-4518.e6. https://doi.org/10.1016/j.cub.2020.08.069 |
| [22] | Casado, S., Varela-Miguéns, M., de Oliveira Diz, T., Quintela-Vilariño, C., Nogueiras, R., Diéguez, C., et al. (2024) The Effects of Ghrelin and LEAP-2 in Energy Homeostasis Are Modulated by Thermoneutrality, High-Fat Diet and Aging. Journal of Endocrinological Investigation, 47, 2061-2074. https://doi.org/10.1007/s40618-024-02307-4 |
| [23] | Sakai, K., Nakazato, Y., Shiimura, Y., Zhang, W. and Nakazato, M. (2025) Ghrelin-Leap2 Interactions along the Stomach–liver Axis. Endocrine Journal, 72, 341-353. https://doi.org/10.1507/endocrj.ej24-0543 |
| [24] | Dutta, B.J., Singh, S., Seksaria, S., Das Gupta, G. and Singh, A. (2022) Inside the Diabetic Brain: Insulin Resistance and Molecular Mechanism Associated with Cognitive Impairment and Its Possible Therapeutic Strategies. Pharmacological Research, 182, Article 106358. https://doi.org/10.1016/j.phrs.2022.106358 |
| [25] | Airapetov, M.I., Eresko, S.O., Lebedev, A.A., Bychkov, E.R. and Shabanov, P.D. (2021) Expression of the Growth Hormone Secretagogue Receptor 1a (GHS‐R1a) in the Brain. Physiological Reports, 9, e15113. https://doi.org/10.14814/phy2.15113 |
| [26] | Liang, Y., Yin, W., Yin, Y. and Zhang, W. (2021) Ghrelin Based Therapy of Metabolic Diseases. Current Medicinal Chemistry, 28, 2565-2576. https://doi.org/10.2174/0929867327666200615152804 |
| [27] | Beuker, C., Schreiner, U., Strecker, J., Altach, E., Rätzel, V., Schmidt-Pogoda, A., et al. (2025) Ghrelin Promotes Neurologic Recovery and Neurogenesis in the Chronic Phase after Experimental Stroke. Neurological Research and Practice, 7, Article No. 14. https://doi.org/10.1186/s42466-025-00371-6 |
| [28] | Zhang, X.X., Tian, Y., Wang, Z.T., Ma, Y.H., Tan, L. and Yu, J. (2021) The Epidemiology of Alzheimer’s Disease Modifiable Risk Factors and Prevention. The Journal of Prevention of Alzheimer’s Disease, 8, 313-321. https://doi.org/10.14283/jpad.2021.15 |
| [29] | Tenchov, R., Sasso, J.M. and Zhou, Q.A. (2024) Alzheimer’s Disease: Exploring the Landscape of Cognitive Decline. ACS Chemical Neuroscience, 15, 3800-3827. https://doi.org/10.1021/acschemneuro.4c00339 |
| [30] | Rout, S., Dash, R., Satish, V., Venugopal, G., Rao, B.N., Bandhyopadhyay, D., Bhoi, S.K. and Ramadass, B. (2025) Exploring the Role of Acylated Ghrelin and Gut Microbiome in Delineating Cognitive Health in the Elderly. Aging, 17, 393-407. |
| [31] | Liu, W., Wu, L., Hu, J. and Gao, Z. (2025) Correlations between Ghrelin Gene Polymorphisms, Cognitive Function, and Activities of Daily Living among Elderly Patients with Alzheimer’s Disease. Annals of Human Biology, 52, Article id: 2507048. https://doi.org/10.1080/03014460.2025.2507048 |
| [32] | Ye, Y., Noche, R.B., Szejko, N., Both, C.P., Acosta, J.N., Leasure, A.C., et al. (2023) A Genome-Wide Association Study of Frailty Identifies Significant Genetic Correlation with Neuropsychiatric, Cardiovascular, and Inflammation Pathways. GeroScience, 45, 2511-2523. https://doi.org/10.1007/s11357-023-00771-z |
| [33] | Abbas, A.K., Lichtman, A.H. and Pillai, S. (2016) Basic Immunology-Functions and Disorders of the Immune System. Elsevier. |
| [34] | Becerra, J. and Duran, I. (2021) Inflammation, a Common Mechanism in Frailty and COVID-19, and Stem Cells as a Therapeutic Approach. Stem Cells Translational Medicine, 10, 1482-1490. https://doi.org/10.1002/sctm.21-0074 |
| [35] | Liu, X., Wei, D. and Li, R. (2023) Ghrelin Attenuates Inflammation in Diabetic Lung Disease by TLR4 Pathway in Vivo and in Vitro. BMJ Open Diabetes Research & Care, 11, e003027. https://doi.org/10.1136/bmjdrc-2022-003027 |
| [36] | Lin, Y., Liang, Z., He, L., Yang, M., Liu, D., Gu, H.F., et al. (2019) Gut Ghrelin Regulates Hepatic Glucose Production and Insulin Signaling via a Gut-Brain-Liver Pathway. Cell Communication and Signaling, 17, Article No. 8. https://doi.org/10.1186/s12964-019-0321-y |
