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慢性肾脏病与衰老暴露组

Chronic Kidney Disease and the Exposome of Ageing.

作者信息

Shiels Paul, Tran Ngoc, McCavitt Jen, Neytchev Ognian, Stenvinkel Peter

机构信息

SoMBS, Davidson Building, University of Glasgow, Glasgow, UK.

Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.

出版信息

Subcell Biochem. 2023;103:79-94. doi: 10.1007/978-3-031-26576-1_5.

Abstract

The gap between improvements in lifespan and age-related health is widening. Globally, the demographic of ageing is increasing and there has emerged a 'diseasome of ageing', typified by a range of non-communicable diseases which share a common underlying component of a dysregulated ageing process. Within this, chronic kidney disease is an emerging global epidemic.The extensive inter-individual variation displayed in how people age and how their diseasome manifests and progresses, has required a renewed focus on their life course exposures and the interplay between the environment and the (epi)genome. Termed the exposome, life course abiotic and biotic factors have a significant impact on renal health.We explore how the exposome of renal ageing can predispose and affect CKD progression. We discuss how the kidney can be used as a model to understand the impact of the exposome in health and chronic kidney disease and how this might be manipulated to improve health span.Notably, we discuss the manipulation of the foodome to mitigate acceleration of ageing processes by phosphate and to explore use of emerging senotherapies. A range of senotherapies, for removing senescent cells, diminishing inflammatory burden and either directly targeting Nrf2, or manipulating it indirectly via modification of the microbiome are discussed.

摘要

寿命延长与年龄相关健康改善之间的差距正在扩大。在全球范围内,老龄化人口正在增加,并且出现了一种“衰老疾病组”,其典型特征是一系列非传染性疾病,这些疾病都有一个共同的潜在因素,即衰老过程失调。其中,慢性肾脏病正在成为一种全球性的流行病。人们衰老的方式以及他们的疾病组如何表现和发展存在广泛的个体差异,这就需要重新关注他们一生的暴露情况以及环境与(表观)基因组之间的相互作用。被称为暴露组的一生非生物和生物因素对肾脏健康有重大影响。我们探讨肾脏衰老的暴露组如何导致和影响慢性肾脏病的进展。我们讨论如何将肾脏用作模型来理解暴露组对健康和慢性肾脏病的影响,以及如何对其进行调控以延长健康寿命。值得注意的是,我们讨论通过调控食物组来减轻磷酸盐对衰老过程的加速作用,并探索新兴的衰老疗法的应用。我们还讨论了一系列衰老疗法,包括清除衰老细胞、减轻炎症负担,以及直接靶向核因子E2相关因子2(Nrf2)或通过改变微生物群间接调控它。

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