MicroRNAs are critical regulators of senescence and aging in mesenchymal stem cells

Potter, Matthew; Hill, William; Isales, Carlos M.; Hamrick, Mark W.; Fulzele, Sadanand

doi:10.1016/j.bone.2020.115679

Cited by 29 publications

(20 citation statements)

References 251 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here we observed that miR-19b-3p expression in the skeletal muscle was decreased with aging. This is similar to previous studies that have reported decreased miR-19b expression in human aging in multiple cell types ( 71 , 84 ). In mice, we observed a higher expression of miR-19b-3p was associated with higher fat-free mass, muscle mass, and strength.…”

Section: Discussionsupporting

confidence: 92%

miR-19b-3p is associated with a diametric response to resistance exercise in older adults and regulates skeletal muscle anabolism via PTEN inhibition

Rivas

Peng

Benard

et al. 2021

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

Our laboratory has discovered that dysregulation in microRNA (miRNA) that target anabolic signaling between younger and older adults is a potential molecular mechanism resulting in age-associated decreases in skeletal muscle mass and function (sarcopenia). Whether differences in miRNA expression profiles account for inter-individual variability in exercise adaptation in older adults is unclear. Understanding paradoxical responses to anabolic stimulation and identifying the mechanisms for this inconsistency in mobility-limited older adults may provide new targets for the treatment of sarcopenia. The objective of the current study was to assess circulating miRNA expression profiles in diametric response of leg lean mass in mobility-limited older individuals after a 6 month progressive resistance exercise training intervention (PRET). Participants were dichotomized by gain (Gainers; n = 33) or loss (Losers; n = 40) of leg lean mass after PRET. Gainers signifcantly increased fat-free mass. Six miRNA (miR-1-3p, miR-19b-3p, miR-92a, miR-126, miR-133a-3p, and miR-133b) were identified to be differentially expressed between Gainers and Losers, with miR-19b-3p being the miRNA most highly associated with increases in fat-free mass. We then used a novel integrative approach to determine if differences in circulating miR-19b-3p potentially translate to augmented anabolic response in human skeletal muscle cells in vitro. Results from this analysis identified that overexpression of miR-19b-3p targeted and downregulated PTEN to facilitate increases in muscle protein synthetic rate. Together these data identify miR-19b-3p as a potent regulator of muscle anabolism that may contribute to an inter-individual response to PRET in mobility-limited older adults.

show abstract

Section: Discussionsupporting

confidence: 92%

miR-19b-3p is associated with a diametric response to resistance exercise in older adults and regulates skeletal muscle anabolism via PTEN inhibition

Rivas

Peng

Benard

et al. 2021

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

show abstract

“…MiRNAs, endogenous small noncoding RNA molecules, have been reported to play crucial roles in mediating the cellular senescence of stem cells [ 24 , 25 , 71 ], examples include microRNA-206 [ 15 ], let-7, miRNA-23a, miRNA-26a, miRNA-30a [ 72 ], microRNA-34a-3p [ 73 ], miRNA-145a [ 27 ], miRNA-1292 [ 26 ], miRNA-15a/15b [ 74 ], miRNA-155-5p [ 43 ], and miRNA-199a-5p [ 49 ]. Using microarray and bioinformatic analysis, we compared miRNA expression levels in OM-MSCs cultured in normoxia and hypoxia.…”

Section: Resultsmentioning

confidence: 99%

Hypoxic preconditioning rejuvenates mesenchymal stem cells and enhances neuroprotection following intracerebral hemorrhage via the miR-326-mediated autophagy

Liu

et al. 2021

Stem Cell Res Ther

View full text Add to dashboard Cite

Background Intracerebral hemorrhage (ICH) is a major public health concern, and mesenchymal stem cells (MSCs) hold great potential for treating ICH. However, the quantity and quality of MSCs decline in the cerebral niche, limiting the potential efficacy of MSCs. Hypoxic preconditioning is suggested to enhance the survival of MSCs and augment the therapeutic efficacy of MSCs in ICH. MicroRNAs (miRNAs) are known to mediate cellular senescence. However, the precise mechanism by which miRNAs regulate the senescence of hypoxic MSCs remains to be further studied. In the present study, we evaluated whether hypoxic preconditioning enhances the survival and therapeutic effects of olfactory mucosa MSC (OM-MSC) survival and therapeutic effects in ICH and investigated the mechanisms by which miRNA ameliorates hypoxic OM-MSC senescence. Methods In the in vivo model, ICH was induced in mice by administration of collagenase IV. At 24 h post-ICH, 5 × 105 normoxia or hypoxia OM-MSCs or saline was administered intracerebrally. The behavioral outcome, neuronal apoptosis, and OM-MSC survival were evaluated. In the in vitro model, OM-MSCs were exposed to hemin. Cellular senescence was examined by evaluating the expressions of P16INK4A, P21, P53, and by β-galactosidase staining. Microarray and bioinformatic analyses were performed to investigate the differences in the miRNA expression profiles between the normoxia and hypoxia OM-MSCs. Autophagy was confirmed using the protein expression levels of LC3, P62, and Beclin-1. Results In the in vivo model, transplanted OM-MSCs with hypoxic preconditioning exhibited increased survival and tissue-protective capability. In the in vitro model, hypoxia preconditioning decreased the senescence of OM-MSCs exposed to hemin. Bioinformatic analysis identified that microRNA-326 (miR-326) expression was significantly increased in the hypoxia OM-MSCs compared with that of normoxia OM-MSCs. Upregulation of miR-326 alleviated normoxia OM-MSC senescence, whereas miR-326 downregulation increased hypoxia OM-MSC senescence. Furthermore, we showed that miR-326 alleviated cellular senescence by upregulating autophagy. Mechanistically, miR-326 promoted the autophagy of OM-MSCs via the PI3K signaling pathway by targeting polypyrimidine tract-binding protein 1 (PTBP1). Conclusions Our study shows that hypoxic preconditioning delays OM-MSC senescence and augments the therapeutic efficacy of OM-MSCs in ICH by upregulating the miR-326/PTBP1/PI3K-mediated autophagy.

show abstract

“…In C2C12 myoblasts, the overexpression of exosomal miR-34a suppresses Sirt1 mRNA and protein expression [71]. miR-34a induces senescence in vascular smooth muscle cells and cardiomyocytes and promotes cardiac fibrosis [72,73]. It has been suggested that with aging and increased exposure to inflammatory factors and ROS, both of which increase OS, miR-34a is upregulated as a 3 Oxidative Medicine and Cellular Longevity consequence of p53 activation, which occurs in cases of sepsis, injury, and inflammation [74].…”

Section: Crosstalk Between Exosomal Mirnas and Os In Opmentioning

confidence: 99%

Role of Exosomal MicroRNAs and Their Crosstalk with Oxidative Stress in the Pathogenesis of Osteoporosis

Lü

Zhang

Liang

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Osteoporosis (OP) is an aging-related disease involving permanent bone tissue atrophy. Most patients with OP show high levels of oxidative stress (OS), which destroys the microstructure of bone tissue and promotes disease progression. Exosomes (exos) help in the delivery of microRNAs (miRNAs) and allow intercellular communication. In OP, exosomal miRNAs modulate several physiological processes, including the OS response. In the present review, we aim to describe how exosomal miRNAs and OS contribute to OP. We first summarize the relationship of OS with OP and then detail the features of exos along with the functions of exo-related miRNAs. Further, we explore the interplay between exosomal miRNAs and OS in OP and summarize the functional role of exos in OP. Finally, we identify the advantages of exo-based miRNA delivery in treatment strategies for OP. Our review seeks to improve the current understanding of the mechanism underlying OP pathogenesis and lay the foundation for the development of novel theranostic approaches for OP.

show abstract

MicroRNAs are critical regulators of senescence and aging in mesenchymal stem cells

Cited by 29 publications

References 251 publications

miR-19b-3p is associated with a diametric response to resistance exercise in older adults and regulates skeletal muscle anabolism via PTEN inhibition

miR-19b-3p is associated with a diametric response to resistance exercise in older adults and regulates skeletal muscle anabolism via PTEN inhibition

Hypoxic preconditioning rejuvenates mesenchymal stem cells and enhances neuroprotection following intracerebral hemorrhage via the miR-326-mediated autophagy

Role of Exosomal MicroRNAs and Their Crosstalk with Oxidative Stress in the Pathogenesis of Osteoporosis

Contact Info

Product

Resources

About