Are microRNAs true sensors of ageing and cellular senescence?

Williams, Joanna M.; Smith, Flint; Kumar, Subodh; Vijayan, Murali; Reddy, P. Hemachandra

doi:10.1016/j.arr.2016.11.008

Cited by 72 publications

(42 citation statements)

References 147 publications

(171 reference statements)

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“…Emerging evidence supports the hypothesis that accumulation of senescent cells or alteration of some age‐related molecules (e.g., miRNA, RNA, lipids, and proteins) packaged by exosomes in the bone microenvironment is the primary cause of osteoporosis (Farr et al., 2017; Gibon, Lu, & Goodman, 2016; Lim et al., 2017; Sui, Hu, Zheng, & Jin, 2016; Williams, Smith, Kumar, Vijayan, & Reddy, 2017). Targeting these exosomes, which act as important communicators between cells, may emerge as a new therapeutic approach for osteoporosis (Liu et al., 2017; Long et al., 2017; Nakano et al., 2016).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐31a‐5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment

et al. 2018

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The alteration of age‐related molecules in the bone marrow microenvironment is one of the driving forces in osteoporosis. These molecules inhibit bone formation and promote bone resorption by regulating osteoblastic and osteoclastic activity, contributing to age‐related bone loss. Here, we observed that the level of microRNA‐31a‐5p (miR‐31a‐5p) was significantly increased in bone marrow stromal cells (BMSCs) from aged rats, and these BMSCs demonstrated increased adipogenesis and aging phenotypes as well as decreased osteogenesis and stemness. We used the gain‐of‐function and knockdown approach to delineate the roles of miR‐31a‐5p in osteogenic differentiation by assessing the decrease of special AT‐rich sequence‐binding protein 2 (SATB2) levels and the aging of BMSCs by regulating the decline of E2F2 and recruiting senescence‐associated heterochromatin foci (SAHF). Notably, expression of miR‐31a‐5p, which promotes osteoclastogenesis and bone resorption, was markedly higher in BMSCs‐derived exosomes from aged rats compared to those from young rats, and suppression of exosomal miR‐31a‐5p inhibited the differentiation and function of osteoclasts, as shown by elevated RhoA activity. Moreover, using antagomiR‐31a‐5p, we observed that, in the bone marrow microenvironment, inhibition of miR‐31a‐5p prevented bone loss and decreased the osteoclastic activity of aged rats. Collectively, our results reveal that miR‐31a‐5p acts as a key modulator in the age‐related bone marrow microenvironment by influencing osteoblastic and osteoclastic differentiation and that it may be a potential therapeutic target for age‐related osteoporosis.

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Section: Discussionmentioning

confidence: 99%

MicroRNA‐31a‐5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment

et al. 2018

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“…Notably, one of the characteristics of aging is epigenetic drift, a subtle but progressive change of the epigenome. [28][29][30] With this in mind, we decided to determine whether successful aging is associated with changes in the expression of sirtuin genes in peripheral blood mononuclear cells (PBMC). We show that even in individuals whose aging is not complicated by age-related diseases, older age is associated with a decreased expression of the majority of the SIRT genes in these cells.…”

Section: Introductionmentioning

confidence: 99%

miR-34a and miR-9 are overexpressed and SIRT genes are downregulated in peripheral blood mononuclear cells of aging humans

Owczarz

Budzinska

Domaszewska-Szostek

et al. 2017

Exp Biol Med (Maywood)

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Impact statementHigh expression of sirtuins, particularly SIRT1, lowers the risk of age-related diseases and probably slows down the rate of aging; therefore, their sustained expression should be one of the features of longevity. However, in this work we show that in peripheral blood mononuclear cells (PBMC) of long-lived individuals, expression of majority of the SIRT genes is significantly lower than in cells of young study subjects. In long-lived individuals, downregulation of SIRT1 coexists with upregulation of SIRT1 mRNA-interacting miR-34a and miR-9, indicating the role of epigenetic drift in age-dependent deregulation of SIRT1 expression. Such constellation of SIRT1, miR-34a, and miR-9 expression in PBMC of successfully aging long-lived individuals indicates that, at least in these individuals, it is not a risk factor for morbidity and mortality. It might however affect the function of the immune system and, therefore, aging individuals can profit from interventions increasing the level of SIRT1. AbstractIncreased expression of sirtuins lowers the risk of age-related diseases, while their role in the regulation of longevity is not firmly established. Since aging is associated with immunosenescence, we tested whether sirtuin expression was modified in peripheral blood mononuclear cells (PBMC) in an age-related manner and whether this might result from altered expression of the selected miRNAs. The expression of seven SIRT genes and of SIRT1 mRNA-interacting miR-9, miR-34a, miR-132, and miR-199a-5p was evaluated by real-time PCR in PBMC originating from young (Y, n ¼ 57, mean age 27 AE 4.3 years), elderly (E, n ¼ 52, 65 AE 3.4 years), and long-lived (L, n ¼ 56, 94 AE 3.5 years) individuals. Older age was associated with a decreased expression of the majority of the SIRT genes. Most severely affected were median expressions of SIRT1 (P ¼ 0.000001 for the whole studied group, Y vs. E: P < 0.000001, Y vs. L: P < 0.000001), and of SIRT3 (P ¼ 0.000001, Y vs. E: P ¼ 0.000004, Y vs. L: P ¼ 0.000028). Older age was also associated with the increased median expression of miR-34a (P ¼ 0.000001, Y vs. E: P ¼ 0.001, Y vs. L: P ¼ 0.000004) and of miR-9 (P ¼ 0.05, Y vs. L: P ¼ 0.054). In functional studies, miR-9 interacted with the 3 0 UTR of SIRT1 mRNA. The SIRT1 mRNA level negatively correlated with the expression of miR34a (r ¼ À0.234, P ¼ 0.003). In conclusion, age-related decrease of SIRT1 expression in PBMC might in part result from overexpression of miR-34a and miR-9. In addition, the sustained expression of the SIRT genes in PBMC is not a prerequisite to longevity in humans but might be one of the reasons for the immune system dysfunction in the elderly.

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“…Ageing is an inevitable event in the development process of all living beings, which is a complex and poorlyunderstood process triggered by progressive cellular senescence in all tissues. miRNAs target many crucial genes and processes that are related to ageing and cellular senescence, including oxidative stress, mitochondrial dysfunction, tumor suppression, neurodegenerative diseases, DNA damage and telomere shortening, which makes miRNA a useful tool as biomarkers of ageing and ageing-related diseases (see reviews in Harries 2014; Williams et al 2017). For instance, miR-1 is implicated in oxidative stress and neurodegenerative diseases, and miR-34a regulates mitochondria dysfunction, tumor suppression and telomere shortening, all of which somehow contribute to the ageing process (Yamakuchi et al 2008;Yang et al 2013;Wu et al 2015).…”

Section: Mirna Functionmentioning

confidence: 99%

Progress and prospects of noncoding RNAs in insects

Xiao

et al. 2019

Journal of Integrative Agriculture

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With the rapid development of high-throughput sequencing technology and bioinformatics algorithms, great progress has been made in the field of noncoding RNA (ncRNA) in the last decade. RNA molecules have been regarded only as a messenger between DNA and protein for decades, but now they have new roles in the biological process as ncRNAs. A growing number of ncRNAs have been identified in insects from the RNA-Seq data of small RNA libraries or transcriptomes. ncRNAs have varied regulatory functions at the epigenetic, transcriptional, or post-transcriptional levels, and participate in almost all types of biological processes. Here, we review the research progress of four kinds of ncRNAs, including microRNA (miRNA), Piwiinteracting RNA (piRNA), circular RNA (circRNA), and long noncoding RNA (lncRNA) in insects. The discovery, biogenesis mechanisms, and regulatory functions of these ncRNAs are presented here to provide a comprehensive understanding of insect ncRNAs and to promote the application of ncRNAs in insect pest control.

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Are microRNAs true sensors of ageing and cellular senescence?

Cited by 72 publications

References 147 publications

MicroRNA‐31a‐5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment

MicroRNA‐31a‐5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment

miR-34a and miR-9 are overexpressed and SIRT genes are downregulated in peripheral blood mononuclear cells of aging humans

Progress and prospects of noncoding RNAs in insects

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