Regulation of Hypoxic Signaling and Oxidative Stress via the MicroRNA–SIRT2 Axis and Its Relationship with Aging-Related Diseases

Kaitsuka, Taku; Matsushita, Masayuki; Matsushita, Nobuko

doi:10.3390/cells10123316

Cited by 10 publications

(7 citation statements)

References 123 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Members of sirtuin family play the key role in aging and age-related disease ( Kaitsuka et al, 2021 ). In the present study, GRb1 could increase the protein levels of SIRT1, SIRT3, SIRT6, and SIRT7 in the small intestines of old mice.…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rb1 improves intestinal aging via regulating the expression of sirtuins in the intestinal epithelium and modulating the gut microbiota of mice

Lei

Chen²,

Hu³

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Intestinal aging seriously affects the absorption of nutrients of the aged people. Ginsenoside Rb1 (GRb1) which has multiple functions on treating gastrointestinal disorders is one of the important ingredients from Ginseng, the famous herb in tradition Chinese medicine. However, it is still unclear if GRb1 could improve intestinal aging. To investigate the function and mechanism of GRb1 on improving intestinal aging, GRb1 was administrated to 104-week-old C57BL/6 mice for 6 weeks. The jejunum, colon and feces were collected for morphology, histology, gene expression and gut microbiota tests using H&E staining, X-gal staining, qPCR, Western blot, immunofluorescence staining, and 16S rDNA sequencing technologies. The numbers of cells reduced and the accumulation of senescent cells increased in the intestinal crypts of old mice, and administration of GRb1 could reverse them. The protein levels of CLDN 2, 3, 7, and 15 were all decreased in the jejunum of old mice, and administration of GRb1 could significantly increase them. The expression levels of Tert, Lgr5, mKi67, and c-Myc were all significantly reduced in the small intestines of old mice, and GRb1 significantly increased them at transcriptional or posttranscriptional levels. The protein levels of SIRT1, SIRT3, and SIRT6 were all reduced in the jejunum of old mice, and GRb1 could increase the protein levels of them. The 16S rDNA sequencing results demonstrated the dysbiosis of the gut microbiota of old mice, and GRb1 changed the composition and functions of the gut microbiota in the old mice. In conclusion, GRb1 could improve the intestinal aging via regulating the expression of Sirtuins family and modulating the gut microbiota in the aged mice.

show abstract

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rb1 improves intestinal aging via regulating the expression of sirtuins in the intestinal epithelium and modulating the gut microbiota of mice

Lei

Chen²,

Hu³

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…The role of SIRTs in EC senescence was also explored in human retinal microvascular ECs (HRECs), where again it was shown that glucose-induced oxidative stress downregulated SIRTs (SIRT3, 4, 5) in vitro and in vivo , increased SIRT-targeting miRNAs and led to early HREC senescence, endothelial-to-mesenchymal transition, and oxidative damage contributing to aging (Liu et al, 2020 ). However, not all SIRTs share the same role, for example SIRT2 was shown to have opposite effects to SIRT1 in the stress response pathway, age-related diseases, and aging (Outeiro et al, 2007 ; Wang Y. et al, 2020 ; Kaitsuka et al, 2021 ).…”

Section: Pathophysiological Mechanisms That Lead To Agingmentioning

confidence: 99%

A Comprehensive Overview of the Complex Role of Oxidative Stress in Aging, The Contributing Environmental Stressors and Emerging Antioxidant Therapeutic Interventions

Iakovou

Kourti

2022

Front. Aging Neurosci.

View full text Add to dashboard Cite

IntroductionAging is a normal, inevitable, irreversible, and progressive process which is driven by internal and external factors. Oxidative stress, that is the imbalance between prooxidant and antioxidant molecules favoring the first, plays a key role in the pathophysiology of aging and comprises one of the molecular mechanisms underlying age-related diseases. However, the oxidative stress theory of aging has not been successfully proven in all animal models studying lifespan, meaning that altering oxidative stress/antioxidant defense systems did not always lead to a prolonged lifespan, as expected. On the other hand, animal models of age-related pathological phenotypes showed a well-correlated relationship with the levels of prooxidant molecules. Therefore, it seems that oxidative stress plays a more complicated role than the one once believed and this role might be affected by the environment of each organism. Environmental factors such as UV radiation, air pollution, and an unbalanced diet, have also been implicated in the pathophysiology of aging and seem to initiate this process more rapidly and even at younger ages.AimThe purpose of this review is to elucidate the role of oxidative stress in the physiology of aging and the effect of certain environmental factors in initiating and sustaining this process. Understanding the pathophysiology of aging will contribute to the development of strategies to postpone this phenomenon. In addition, recent studies investigating ways to alter the antioxidant defense mechanisms in order to prevent aging will be presented.ConclusionsCareful exposure to harmful environmental factors and the use of antioxidant supplements could potentially affect the biological processes driving aging and slow down the development of age-related diseases. Maybe a prolonged lifespan could not be achieved by this strategy alone, but a longer healthspan could also be a favorable target.

show abstract

“…Sirtuin 2 (SIRT2) and nuclear factor erythroid 2-related factor 2 (NRF2), two direct targets of miR-140-5p, may strongly participate in oxidative stress in AS. The mechanistic role of SIRT2 in oxidative stress remains unclear as SIRT2 regulates hypoxia inducible factor 1 (HIF1) expression, but its positive regulation (stabilization) or negative regulation (degradation) is still debated [ 61 , 62 ]. In response to oxidative conditions, NRF2 is translocated into the nucleus, where it acts as a transcription factor activating anti-oxidative gene transcription [ 61 , 63 ].…”

Section: Role Of Mir-140-5p/-3p In Atherosclerosismentioning

confidence: 99%

miR-140-5p and miR-140-3p: Key Actors in Aging-Related Diseases?

Toury

Frankel

Airault

et al. 2022

IJMS

View full text Add to dashboard Cite

microRNAs (miRNAs) are small single strand non-coding RNAs and powerful gene expression regulators. They mainly bind to the 3′UTR sequence of targeted mRNA, leading to their degradation or translation inhibition. miR-140 gene encodes the pre-miR-140 that generates the two mature miRNAs miR-140-5p and miR-140-3p. miR-140-5p/-3p have been associated with the development and progression of cancers, but also non-neoplastic diseases. In aging-related diseases, miR-140-5p and miR-140-3p expressions are modulated. The seric levels of these two miRNAs are used as circulating biomarkers and may represent predictive tools. They are also considered key actors in the pathophysiology of aging-related diseases. miR-140-5p/-3p repress targets regulating cell proliferation, apoptosis, senescence, and inflammation. This work focuses on the roles of miR-140-3p and miR-140-5p in aging-related diseases, details their regulation (i.e., by long non-coding RNA), and reviews the molecular targets of theses miRNAs involved in aging pathophysiology.

show abstract

Regulation of Hypoxic Signaling and Oxidative Stress via the MicroRNA–SIRT2 Axis and Its Relationship with Aging-Related Diseases

Cited by 10 publications

References 123 publications

Ginsenoside Rb1 improves intestinal aging via regulating the expression of sirtuins in the intestinal epithelium and modulating the gut microbiota of mice

Ginsenoside Rb1 improves intestinal aging via regulating the expression of sirtuins in the intestinal epithelium and modulating the gut microbiota of mice

A Comprehensive Overview of the Complex Role of Oxidative Stress in Aging, The Contributing Environmental Stressors and Emerging Antioxidant Therapeutic Interventions

miR-140-5p and miR-140-3p: Key Actors in Aging-Related Diseases?

Contact Info

Product

Resources

About