MicroRNAs, DNA damage response and ageing

Majidinia, Maryam; Mir, Seyed Mostafa; Mirza-Aghazadeh-Attari, Mohammad; Asghari, Roghaieh; Kafil, Hossein Samadi; Safa, Amin; Mahmoodpoor, Ata; Yousefi, Bahman

doi:10.1007/s10522-020-09862-2

Cited by 28 publications

(16 citation statements)

References 157 publications

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“…MicroRNAs play a critical role in the coordination of DNA damage response [ 917 ]. In particular, they regulate the activity of DNA damage sensors (ATM, ATR, RAD9, RAD1) and NER enzymes (RPA, XPC) [ 918 ]. Since microRNAs have multiple targets in cell networks, their regulation allows influencing signaling pathways of aging and age-related diseases [ 128 ].…”

Section: Pharmacological Interventions Protecting Genomementioning

confidence: 99%

Genome-Protecting Compounds as Potential Geroprotectors

Proshkina

Shaposhnikov

Moskalev

2020

IJMS

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Throughout life, organisms are exposed to various exogenous and endogenous factors that cause DNA damages and somatic mutations provoking genomic instability. At a young age, compensatory mechanisms of genome protection are activated to prevent phenotypic and functional changes. However, the increasing stress and age-related deterioration in the functioning of these mechanisms result in damage accumulation, overcoming the functional threshold. This leads to aging and the development of age-related diseases. There are several ways to counteract these changes: (1) prevention of DNA damage through stimulation of antioxidant and detoxification systems, as well as transition metal chelation; (2) regulation of DNA methylation, chromatin structure, non-coding RNA activity and prevention of nuclear architecture alterations; (3) improving DNA damage response and repair; (4) selective removal of damaged non-functional and senescent cells. In the article, we have reviewed data about the effects of various trace elements, vitamins, polyphenols, terpenes, and other phytochemicals, as well as a number of synthetic pharmacological substances in these ways. Most of the compounds demonstrate the geroprotective potential and increase the lifespan in model organisms. However, their genome-protecting effects are non-selective and often are conditioned by hormesis. Consequently, the development of selective drugs targeting genome protection is an advanced direction.

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Section: Pharmacological Interventions Protecting Genomementioning

confidence: 99%

Genome-Protecting Compounds as Potential Geroprotectors

Proshkina

Shaposhnikov

Moskalev

2020

IJMS

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“…However, many theories currently exist regarding the mechanisms that underpin aging. Indeed it has been suggested that DNA damage response [3], autophagy [4], telomerase length [5], and free radicals all play a part in the aging process [6]. Furthermore, studies have shown that senescence can result in proinflammatory phenotypes, including elevated levels of typical inflammatory markers such as interleukin-1 (IL-1) [7], IL-6, and tumor necrosis factor (TNF-α); increases in the levels of these markers can indicate senescence [8,9].…”

Section: Introductionmentioning

confidence: 99%

Liuweidihuang Pill Alleviates Inflammation of the Testis via AMPK/SIRT1/NF‐κB Pathway in Aging Rats

Wang

Zhou

Yang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Liuweidihuang Pill (LP) is a traditional Chinese herbal formula that is often used in clinical practice to treat kidney deficiency syndrome. The present study investigated the antiaging effects of LP in a D-galactose- (D-Gal-) induced subacute aging rat model. The study also attempted to explore whether anti-inflammatory mechanisms that underpin the antiaging effects are mediated by the AMPK/SIRT1/NF-κB signaling pathway. Rats were subcutaneously injected with D-Gal at a dosage of 100 mg/kg/d for 8 weeks. Upon successful induction of aging in the rats, the animal was administered LP at 0.9 g/kg/d by gavage for 4 weeks. Proteins of the testis were subsequently examined by western blot analysis, and associated locations in the testicular tissue were determined by immunohistochemistry. We observed that LP exerted antiaging effects in aging rats following the activation of AMPK/SIRT1. It was also observed that LP inhibited the expression of NF-κB, thereby further attenuating inflammation of the testis. Therefore, LP can alleviate inflammation of the testis via the AMPK/SIRT1/NF-κB pathway in aging rats.

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“…In addition, VSMC senescence was attenuated by miR-665 inhibition. Moreover, miR-665 regulated VSMC senescence via interacting with lncRNA GAS5 Several studies demonstrate that the functional changes of miRNAs affect the expression of aging-related genes through regulating key molecular pathways (Kim et al, 2017;Majidinia et al, 2020). The aberrant expressions of miR-21, miR-155, miR-126, miR-146a/b, miR-143/145, miR-223, and miR-221 were found in aging-associated CVD (Gangwar et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

MiR-665 Regulates Vascular Smooth Muscle Cell Senescence by Interacting With LncRNA GAS5/SDC1

Chen

Liang

et al. 2021

Front. Cell Dev. Biol.

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Background: Vascular aging is considered a special risk factor for cardiovascular diseases, and vascular smooth muscle cells (VSMCs) play a major role in aging-related vascular remodeling and in the pathological process of atherosclerosis. Recent research has reported that long non-coding RNA/microRNA (lncRNA/miRNA) is a critical regulator of cellular senescence. However, the role and mechanism of lncRNA GAS5/miR-665 axis in VSMC senescence remain incompletely understood.Methods: Cellular senescence was evaluated using senescence-associated β-gal activity, the NAD+/NADH ratio, and by immunofluorescence staining of γH2AX immunofluorescence. Differentially expressed miRNAs (DEMs) were identified by miRNA microarray assays and subsequently validated by quantitative real-time PCR (qRT-PCR). A dual luciferase reporter assay was conducted to confirm the binding of lncRNA GAS5 and miR-665 as well as miR-665 and syndecan 1 (SDC1). Serum levels of miR-665, lncRNA GAS5, and SDC1 in 93 subjects were detected by qRT-PCR. The participants were subdivided into control, aging, and early vascular aging (EVA) groups, and their brachial-ankle pulse wave velocity (baPWV) was measured.Results: A total of 20 overlapping DEMs were identified in young and old VSMCs via microarray analysis. MiR-665 showed a significant alteration and, therefore, was selected for further analysis. Upregulation of miR-665 was found in aging VSMCs, and downregulation of miR-665 caused an inhibition of VSMCs senescence. Subsequently, the dual luciferase reporter assay determined the binding site of miR-665 with the 3′-UTR of lncRNA GAS5 and SDC1. Increased expression of lncRNA GAS5 expression inhibited the miR-665 level and VSMC senescence. However, as shown in rescue experiment results, either miR-665 overexpression or SDC1 knockdown significantly reversed the effects of lncRNA GAS5 on VSMC senescence. Finally, compared with that of the control group, miR-665 was highly expressed in serum samples in the aging and EVA groups, especially in the EVA groups. On the contrary, serum levels of lncRNA GAS5 and SDC1 were lower in these two groups. Collectively, in the aging and EVA groups, miR-665 expression was negatively correlated with lncRNA GAS5 and SDC1 expression.Conclusion: miR-665 inhibition functions as a vital modulator of VSMC senescence by negatively regulating SDC1, which is achieved by lncRNA GAS5 that sponges miR-665. Our findings may provide a new treatment strategy for aging-related cardiovascular diseases.

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MicroRNAs, DNA damage response and ageing

Cited by 28 publications

References 157 publications

Genome-Protecting Compounds as Potential Geroprotectors

Genome-Protecting Compounds as Potential Geroprotectors

Liuweidihuang Pill Alleviates Inflammation of the Testis via AMPK/SIRT1/NF‐κB Pathway in Aging Rats

MiR-665 Regulates Vascular Smooth Muscle Cell Senescence by Interacting With LncRNA GAS5/SDC1

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