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免疫代谢与衰老过程中的免疫衰老交汇。

Intersection of immunometabolism and immunosenescence during aging.

机构信息

Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, 4-108 Nils Hasselmo Hall, University of Minnesota, Minneapolis, MN, USA.

Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, 4-108 Nils Hasselmo Hall, University of Minnesota, Minneapolis, MN, USA.

出版信息

Curr Opin Pharmacol. 2021 Apr;57:107-116. doi: 10.1016/j.coph.2021.01.003. Epub 2021 Mar 5.

Abstract

Aging is associated with the highest risk for morbidity and mortality to chronic or metabolic diseases, which are present in 50% of the elderly. Improving metabolic and immune function of the elderly would improve quality of life and reduce the risk for all other diseases. Tissue-resident macrophages and the NLRP3 inflammasome are established drivers of inflammaging and metabolic dysfunction. Energy-sensing signaling pathways connect sterile and metabolic inflammation with cellular senescence and tissue dysfunction. We discuss recent advances in the immunometabolism field. Common themes revealed by recent publications include the alterations in metabolic signaling (SIRTUIN, AMPK, or mTOR pathways) in aged immune cells, the impact of senescence on inflammaging and tissue dysfunction, and the age-related changes in metabolic tissues, especially adipose tissue, as an immunological organ. Promising gerotherapeutics are candidates to broadly target nutrient and energy sensing, inflammatory and senescence pathways, and have potential to improve healthspan and treat age-related diseases.

摘要

衰老是与慢性病或代谢病的发病率和死亡率的最高风险相关的,这些疾病在 50%的老年人中存在。改善老年人的代谢和免疫功能将提高生活质量,并降低所有其他疾病的风险。组织驻留巨噬细胞和 NLRP3 炎性小体是炎症衰老和代谢功能障碍的既定驱动因素。能感知能量的信号通路将非传染性炎症和代谢炎症与细胞衰老和组织功能障碍联系起来。我们讨论了免疫代谢领域的最新进展。最近出版物揭示的共同主题包括衰老免疫细胞中代谢信号(SIRTUIN、AMPK 或 mTOR 通路)的改变、衰老对炎症衰老和组织功能障碍的影响,以及代谢组织(尤其是脂肪组织)作为免疫器官的年龄相关性变化。有前途的衰老治疗剂是广泛靶向营养和能量感知、炎症和衰老途径的候选药物,有潜力改善健康寿命并治疗与年龄相关的疾病。

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本文引用的文献

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Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span.衰老细胞清除药物:降低衰老细胞活力以延长健康寿命。
Annu Rev Pharmacol Toxicol. 2021 Jan 6;61:779-803. doi: 10.1146/annurev-pharmtox-050120-105018. Epub 2020 Sep 30.
2
SIRT1 is downregulated by autophagy in senescence and ageing.自噬在衰老和老化过程中使 SIRT1 下调。
Nat Cell Biol. 2020 Oct;22(10):1170-1179. doi: 10.1038/s41556-020-00579-5. Epub 2020 Sep 28.
8
Ageing hallmarks exhibit organ-specific temporal signatures.衰老特征表现出器官特异性的时相特征。
Nature. 2020 Jul;583(7817):596-602. doi: 10.1038/s41586-020-2499-y. Epub 2020 Jul 15.

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