竞争性内源性 RNA 网络与老年雄性小鼠骨骼肌中的脂肪积累有关

IF 5.3 3区 医学 Q2 CELL BIOLOGY Mechanisms of Ageing and Development Pub Date : 2024-06-03 DOI:10.1016/j.mad.2024.111953
Yuxiao Liao , Zhao Peng , Xiaolei Zhou , Huanhuan Zhou , Zitong Meng , Shiyin Xu , Taoping Sun , Andreas K. Nüssler , Wei Yang
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引用次数: 0

摘要

肌肉老化会导致虚弱、跌倒和骨折等严重后果,从而增加老年人的发病率和死亡率。转录后调控,尤其是竞争性内源性 RNA(ceRNA)机制可能会调节骨骼肌的衰老过程。研究人员对6个月大(成年)和22个月大(老年)雄性小鼠的股四头肌进行了RNA-seq分析,以确定差异表达的ncRNA和mRNA,并进一步构建ceRNA网络。结果发现,老龄小鼠的股四头肌体重比和肌纤维横截面积均有所下降,并具有衰老的组织学特征。此外,与成年小鼠相比,老龄小鼠股四头肌中atrogin-1和MuRF-1的表达量较高,而Myog、Myf4和Myod1的表达量较低。两组小鼠股四头肌中有85个lncRNA、52个circRNA、10个miRNA和277个mRNA表达明显失调,其中构建了两个ceRNA网络lncRNA 2700081O15Rik/circRNA_0000820-miR-673-3p-Tmem120b。与成年小鼠相比,老龄小鼠股四头肌中甘油三酯水平及PPARγ、C/EBPα、FASN和瘦素的表达升高,脂肪连素的表达降低。LncRNA 2700081O15Rik/circRNA_0000820-miR-673-3p-Tmem120b可能与老年雄性小鼠骨骼肌的脂肪生成和脂肪堆积有关。
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Competing endogenous RNA networks were associated with fat accumulation in skeletal muscle of aged male mice

Muscle aging contributed to morbidity and mortality in the elderly adults by leading to severe outcomes such as frailty, falls and fractures. Post-transcriptional regulation especially competing endogenous RNA (ceRNA) mechanism may modulate the process of skeletal muscle aging. RNA-seq was performed in quadriceps of 6-month-old (adult) and 22-month-old (aged) male mice to identify differentially expressed ncRNAs and mRNAs and further construct ceRNA networks. Decreased quadriceps-body weight ratio and muscle fiber cross-sectional area as well as histological characteristics of aging were observed in the aged mice. Besides, there were higher expressions of atrogin-1 and MuRF-1 and lower expression of Myog, Myf4 and Myod1 in the quadriceps of aged mice relative to that of adult mice. The expression of 85 lncRNAs, 52 circRNAs, 10 miRNAs and 277 mRNAs were significantly dysregulated in quadriceps between the two groups, among which two ceRNA networks lncRNA 2700081O15Rik/circRNA_0000820-miR-673–3p-Tmem120b were constructed. Level of triglycerides and expression of PPARγ, C/EBPα, FASN and leptin were elevated and the expression of adiponectin was reduced in quadriceps of aged mice compared with that of adult mice. LncRNA 2700081O15Rik/circRNA_0000820-miR-673–3p-Tmem120b were possibly associated with the adipogenesis and fat accumulation in skeletal muscle of age male mice.

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来源期刊
CiteScore
11.10
自引率
1.90%
发文量
79
审稿时长
32 days
期刊介绍: Mechanisms of Ageing and Development is a multidisciplinary journal aimed at revealing the molecular, biochemical and biological mechanisms that underlie the processes of aging and development in various species as well as of age-associated diseases. Emphasis is placed on investigations that delineate the contribution of macromolecular damage and cytotoxicity, genetic programs, epigenetics and genetic instability, mitochondrial function, alterations of metabolism and innovative anti-aging approaches. For all of the mentioned studies it is necessary to address the underlying mechanisms. Mechanisms of Ageing and Development publishes original research, review and mini-review articles. The journal also publishes Special Issues that focus on emerging research areas. Special issues may include all types of articles following peered review. Proposals should be sent directly to the Editor-in-Chief.
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