Polr3b heterozygosity in mice induces both beneficial and deleterious effects on health during ageing with no effect on lifespan
Polr3b heterozygosity in mice induces both beneficial and deleterious effects on health during ageing with no effect on lifespan
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DOI：
10.1111/acel.14141
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发表时间：
2024-03-11
期刊：
影响因子：
7.8
通讯作者：
Selman，Colin
中科院分区：
文献类型：
--
作者：
Borland，Gillian;Wilkie，Stephen E.;Selman，Colin
在多细胞生物中调节衰老的遗传途径通常在广泛的进化距离中高度保守。最近RNA聚合酶III（Pol III）被证明可以促进酵母的衰老，C。elegans和D.黑腹菌在这项研究中，我们研究了Pol III在哺乳动物衰老中的作用，使用了Pol III杂合子（Polr 3b +/−）的C57 BL/6 N小鼠。我们确定了Polr 3b +/−突变对健康的性二态性、器官特异性有益和有害影响。雌性Polr 3b +/−小鼠在衰老过程中表现出改善的骨骼健康，但它们维持有效肠道屏障功能的能力受到损害，并且它们易患特发性皮炎（ID）。相比之下，malePolr 3b +/−小鼠比野生型（WT）雄性更轻，并且在老年时肠道屏障功能显著改善。几个代谢参数受年龄和性别的影响，但没有检测到基因型差异。与WT对照组相比，雄性和雌性Polr 3b +/−小鼠的寿命均不长。总体而言，我们没有发现任何证据表明降低Pol III活性可以延长小鼠寿命，但我们确实发现了一些潜在的器官和性别特异性益处。
The genetic pathways that modulate ageing in multicellular organisms are typically highly conserved across wide evolutionary distances. Recently RNA polymerase III (Pol III) was shown to promote ageing in yeast,C. elegansandD. melanogaster. In this study we investigated the role of Pol III in mammalian ageing using C57BL/6N mice heterozygous for Pol III (Polr3b+/−). We identified sexually dimorphic, organ‐specific beneficial as well as detrimental effects of thePolr3b+/−mutation on health. FemalePolr3b+/−mice displayed improved bone health during ageing, but their ability to maintain an effective gut barrier function was compromised and they were susceptible to idiopathic dermatitis (ID). In contrast, malePolr3b+/−mice were lighter than wild‐type (WT) males and had a significantly improved gut barrier function in old age. Several metabolic parameters were affected by both age and sex, but no genotype differences were detected. Neither male nor femalePolr3b+/−mice were long‐lived compared to WT controls. Overall, we find no evidence that a reduced Pol III activity extends mouse lifespan but we do find some potential organ‐ and sex‐specific benefits for old‐age health.