MicroRNA-570 is a novel regulator of cellular senescence and inflammaging

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Jonathan R BakerPeter J Barnes

Abstract

Diseases of accelerated aging often occur together (multimorbidity), and their prevalence is increasing, with high societal and health care costs. Chronic obstructive pulmonary disease (COPD) is one such condition, in which one half of patients exhibit ≥4 age-related diseases. Diseases of accelerated aging share common molecular pathways, which lead to the detrimental accumulation of senescent cells. These senescent cells no longer divide but release multiple inflammatory proteins, known as the senescence-associated secretory phenotype, which may perpetuate and speed disease. Here, we show that inhibiting miR-570-3p, which is increased in COPD cells, reverses cellular senescence by restoring the antiaging molecule sirtuin-1. MiR-570-3p is induced by oxidative stress in airway epithelial cells through p38 MAP kinase-c-Jun signaling and drives senescence by inhibiting sirtuin-1. Inhibition of elevated miR-570-3p in COPD small airway epithelial cells, using an antagomir, restores sirtuin-1 and suppresses markers of cellular senescence (p16INK4a, p21Waf1, and p27Kip1), thereby restoring cellular growth by allowing progression through the cell cycle. MiR-570-3p inhibition also suppresses the senescence-associated secretory phenotype...Continue Reading

Associated Clinical Trials

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Citations

Jun 9, 2019·International Journal of Molecular Sciences·Pauline HenrotIsabelle Dupin
Jan 10, 2020·Journal of Cellular and Molecular Medicine·Bingru ZhouPing Zou
Mar 13, 2019·American Journal of Respiratory and Critical Care Medicine·Peter J BarnesLouise E Donnelly
Aug 16, 2019·International Journal of Molecular Sciences·Giuseppe MurdacaSebastiano Gangemi
Aug 23, 2020·Journal of Clinical Medicine·Yosuke FukudaHironori Sagara
Dec 4, 2020·Neural Regeneration Research·Shi-Jia YuJuan Feng
May 26, 2020·Mechanisms of Ageing and Development·Xingjie MaWeili Liu
Jan 8, 2021·European Respiratory Review : an Official Journal of the European Respiratory Society·Peter J BarnesMaria G Belvisi
Jan 21, 2020·Experimental Gerontology·Rui-Ming Liu, Gang Liu
Mar 26, 2021·Frontiers in Cell and Developmental Biology·Hao ZhuQiang Shen
Sep 28, 2020·Nanomedicine : Nanotechnology, Biology, and Medicine·Meenu MehtaKamal Dua
Apr 4, 2021·Cell·Jaime L SchneiderMarcia C Haigis
Apr 16, 2021·Frontiers in Cell and Developmental Biology·Ruchi Kumari, Parmjit Jat
Aug 6, 2021·Mechanisms of Ageing and Development·Utkarsh TripathiJames L Kirkland
Aug 28, 2021·Biomedicines·Yousra HamdanGabriel Malka

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Methods Mentioned

BETA
PCR
Assay
flow cytometry
zymography
ELISA
biosensor
bronchoalveolar lavage
acetylation

Software Mentioned

GraphPad Prism
TargetScan
MiRanda

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