Blood circulating miR-28-5p and let-7d-5p associate with premature ageing in Down syndrome

Morsiani, Cristina; Bacalini, Maria Giulia; Collura, Salvatore; Moreno‐Villanueva, María; Breusing, Nicolle; Bürkle, Alexander; Grune, Tilman; Franceschi, Claudio; Eguileor, Magda de; Capri, Miriam

doi:10.1016/j.mad.2022.111691

Cited by 12 publications

(6 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…One may wonder about the rationale of using very strong overexpression in this study to mimic the functional consequence of about twofolds of miR‐134‐5p difference between young and senescent EPCs. Since cell culture experiments only allowed hours or days to evaluate the effects of microRNA, considering years of time for EPCs to face the up‐regulation of miR‐134‐5p during the ageing process, we think it is reasonable using very strong miR‐134‐5p overexpression to represent the long‐term effects, similar to previous reports in various research fields, 6 , 42 , 47 , 48 , 49 , 50 , 51 , 52 , 53 in which the microRNA expression fold changes between cells and their control groups usually ranged from twofold to 20‐folds, while in the forced expression experiments in vitro the microRNA expression levels after forced expression could be as high as more than a few 100‐fold. In our study, TGF‐β1 protein level was proved to be down‐regulated in senescent EPCs‐derived supernatant by ELISA.…”

Section: Discussionsupporting

confidence: 75%

“… 52 More recently, circulating miR‐28‐5p and let‐7d‐5p were identified as potential biomarkers of the premature ageing in individuals with Down syndrome before the age of 50 years, as their levels declined earlier compared to non‐trisomic physiological ageing. 53 Circulating miR‐29b decreased in response to sarcopenia in older Chinese patients with cardiovascular risk factors and could be considered as a possible biomarker for sarcopenia. 57 In our previous research, hsa‐miR‐409‐3p was up‐regulated in senescent EPCs, acting as a negative modulator of angiogenesis and could be a potential biomarker for human ageing.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Hsa‐miR‐134‐5p predicts cardiovascular risk in circulating mononuclear cells and improves angiogenic action of senescent endothelial progenitor cells

Tien,

Wu,

Chang

et al. 2024

J Cellular Molecular Medi

View full text Add to dashboard Cite

This research explores the role of microRNA in senescence of human endothelial progenitor cells (EPCs) induced by replication. Hsa‐miR‐134‐5p was found up‐regulated in senescent EPCs where overexpression improved angiogenic activity. Hsa‐miR‐134‐5p, which targeted transforming growth factor β‐activated kinase 1‐binding protein 1 (TAB1) gene, down‐regulated TAB1 protein, and inhibited phosphorylation of p38 mitogen‐activated protein kinase (p38) in hsa‐miR‐134‐5p‐overexpressed senescent EPCs. Treatment with siRNA specific to TAB1 (TAB1si) down‐regulated TAB1 protein and subsequently inhibited p38 activation in senescent EPCs. Treatment with TAB1si and p38 inhibitor, respectively, showed angiogenic improvement. In parallel, transforming growth factor Beta 1 (TGF‐β1) was down‐regulated in hsa‐miR‐134‐5p‐overexpressed senescent EPCs and addition of TGF‐β1 suppressed the angiogenic improvement. Analysis of peripheral blood mononuclear cells (PBMCs) disclosed expression levels of hsa‐miR‐134‐5p altered in adult life, reaching a peak before 65 years, and then falling in advanced age. Calculation of the Framingham risk score showed the score inversely correlates with the hsa‐miR‐134‐5p expression level. In summary, hsa‐miR‐134‐5p is involved in the regulation of senescence‐related change of angiogenic activity via TAB1‐p38 signalling and via TGF‐β1 reduction. Hsa‐miR‐134‐5p has a potential cellular rejuvenation effect in human senescent EPCs. Detection of human PBMC‐derived hsa‐miR‐134‐5p predicts cardiovascular risk.

show abstract

Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Hsa‐miR‐134‐5p predicts cardiovascular risk in circulating mononuclear cells and improves angiogenic action of senescent endothelial progenitor cells

Tien,

Wu,

Chang

et al. 2024

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…Despite some progress in brain imaging and CSF-based biomarkers ( Snyder et al, 2020 ), specific diagnostic or prognostic AD biomarkers for DS are not yet available ( Lorenzon et al, 2023 ). Although CSF is considered a precise representation of brain changes, blood-based biomarkers offer a more accessible and less invasive method for detecting peripheral alterations early in AD ( Petersen and O'Bryant, 2019 ; Morsiani et al, 2022 ). Along this line, it has been recently demonstrated by Pentz et al that alterations in the brain nerve growth factor (NGF) metabolism are strictly reflected in both the plasma and CSF from individuals with DS ( Carmona-Iragui et al, 2021 ; Pentz et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Low TGF-β1 plasma levels are associated with cognitive decline in Down syndrome

Grasso,

Fidilio,

L’Episcopo

et al. 2024

Front. Pharmacol.

Self Cite

View full text Add to dashboard Cite

Almost all individuals with Down’s syndrome (DS) show the characteristic neuropathological features of Alzheimer’s disease (AD) by the age of 40, yet not every individual with DS experiences symptoms of AD later in life. Similar to neurotypical developing subjects, AD in people with DS lasts for a long preclinical phase in which biomarkers follow a predictable order of changes. Hence, a prolonged asymptomatic period precedes the onset of dementia, underscoring the importance of identifying new biomarkers for the early detection and monitoring of cognitive decline in individuals with DS. Blood-based biomarkers may offer an alternative non-invasive strategy for the detection of peripheral biological alterations paralleling nervous system pathology in an early phase of the AD continuum. In the last few years, a strong neurobiological link has been demonstrated between the deficit of transforming growth factor-β1 (TGF-β1) levels, an anti-inflammatory cytokine endowed with neuroprotective activity, and early pro-inflammatory processes in the AD brain. In this clinical prospective observational study, we found significant lower plasma TGF-β1 concentrations at the first neuropsychological evaluation (baseline = T0) both in young adult DS individuals (19–35 years) and older DS subjects without AD (35–60 years) compared to age- and sex-matched healthy controls. Interestingly, we found that the lower TGF-β1 plasma concentrations at T0 were strongly correlated with the following cognitive decline at 12 months. In addition, in young individuals with DS, we found, for the first time, a negative correlation between low TGF-β1 concentrations and high TNF-α plasma concentrations, a pro-inflammatory cytokine that is known to be associated with cognitive impairment in DS individuals with AD. Finally, adopting an ex vivo approach, we found that TGF-β1 concentrations were reduced in parallel both in the plasma and in the peripheral blood mononuclear cells (PBMCs) of DS subjects, and interestingly, therapeutic concentrations of fluoxetine (FLX) applied to cultured PBMCs (1 µM for 24 h) were able to rescue TGF-β1 concentrations in the culture media from DS PBMCs, suggesting that FLX, a selective serotonin reuptake inhibitor (SSRI) endowed with neuroprotective activity, might rescue TGF-β1 concentrations in DS subjects at higher risk to develop cognitive decline.

show abstract

“…MiR-374 нацелена на мРНК генов ATM (кодирует серин-треониновую киназу ATM), BCL2 (кодирует регулятор апоптоза BCL2), CDKN1A (кодирует ингибитор циклин-зависимой киназы 1А), CISH (кодирует SH2-содержащий белок, индуцируемый цитокинами), EP300 (кодирует E1A связывающий протеин p300), HMGB2 (кодирует групповой бокс высокой мобильности 2), PARP1 (кодирует поли(АДФ-риоза) полимеразу 1), TP73 (кодирует опухолевый белок p73) [65]. Среди циркулирующих микроРНК при физиологическом старении определено снижение уровня miR-28 [66]. Определена роль повышенной экспрессии miR-31 в старении кожи, которая напрямую воздействует на мРНК гена циркадных часов Clock, что приводит к активации каскада MAPK/ERK и истощению стволовых клеток фолликулов волос кожи [67].…”

Section: ассоциация со старением произошедших от ретроэлементов микро...unclassified

Role of MicroRNAs and Retroelements in the Pathogenesis of Atherosclerosis

Mustafin,

Galieva

2024

Arhivʺ vnutrennej mediciny

View full text Add to dashboard Cite

Atherosclerosis is the leading cause of cardiovascular disease among adults. The incidence of atherosclerosis increases significantly with age, which indicates the possible influence of aging mechanisms on the development of the disease, including changes in epigenetic factors caused by pathological activation of transposable elements. Triggers of atherosclerosis are also viral infections, which promote the expression of retroelements that stimulate the interferon response with the development of chronic inflammation. Activated retroelements also alter the regulation of immune system genes and epigenetic factors, including the pathological production of microRNAs and long non-coding RNAs. A promising direction for atherosclerosis treatment is the epigenetic impact on the expression of specific genes involved in the pathogenesis of atherosclerosis using small interfering RNAs. In this regard, the drugs inclisiran and olpasiran have undergone clinical trials and have shown their effectiveness. Therefore, it is important to search for new molecular targets in this direction, which can serve as transposons, which are sources of non-coding RNAs. Changes in the activity of retroelements during aging have a global regulatory effect on the functioning of the entire genome, contributing to the development of age-associated pathology. An analysis of the scientific literature made it possible to identify 29 microRNAs derived from retroelements, changes in the expression of which have been identified both during aging and atherosclerosis. These microRNAs can be used as tools for prolonging life and treating cardiovascular pathology. The results obtained also indicate that retroelements pathologically activated during aging cause the development of atherosclerosis.

show abstract

Blood circulating miR-28-5p and let-7d-5p associate with premature ageing in Down syndrome

Cited by 12 publications

References 45 publications

Hsa‐miR‐134‐5p predicts cardiovascular risk in circulating mononuclear cells and improves angiogenic action of senescent endothelial progenitor cells

Hsa‐miR‐134‐5p predicts cardiovascular risk in circulating mononuclear cells and improves angiogenic action of senescent endothelial progenitor cells

Low TGF-β1 plasma levels are associated with cognitive decline in Down syndrome

Role of MicroRNAs and Retroelements in the Pathogenesis of Atherosclerosis

Contact Info

Product

Resources

About