Senescence-associated lysosomalα-L-fucosidase (SA-α-Fuc): A sensitive and more robust biomarker for cellular senescence beyond SA-β-Gal

Singh, Madhurendra; Piekorz, Roland P.

doi:10.4161/cc.25318

Cited by 22 publications

(17 citation statements)

References 8 publications

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“…Senescence is characterized by a large, flatter cell morphology and senescence-associated b-galactosidase (SA-b-gal) expression [26]. GDM-UC-MSCs exhibited increased SA-b-gal staining, which was detected cytochemically as blue perinuclear staining ( Fig.…”

Section: Gdm-uc-mscs Undergo Premature Senescencementioning

confidence: 99%

Umbilical Cord Mesenchymal Stromal Cells Affected by Gestational Diabetes Mellitus Display Premature Aging and Mitochondrial Dysfunction

Kim

Piao

Pak

et al. 2015

Stem Cells and Development

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Human umbilical cord mesenchymal stromal cells (hUC-MSCs) of Wharton's jelly origin undergo adipogenic, osteogenic, and chondrogenic differentiation in vitro. Recent studies have consistently shown their therapeutic potential in various human disease models. However, the biological effects of major pregnancy complications on the cellular properties of hUC-MSCs remain to be studied. In this study, we compared the basic properties of hUC-MSCs obtained from gestational diabetes mellitus (GDM) patients (GDM-UC-MSCs) and normal pregnant women (N-UC-MSCs). Assessments of cumulative cell growth, MSC marker expression, cellular senescence, and mitochondrial function-related gene expression were performed using a cell count assay, senescence-associated b-galactosidase staining, quantitative real-time reverse transcription-polymerase chain reaction, immunoblotting, and cell-based mitochondrial functional assay system. When compared with N-UCMSCs, GDM-UC-MSCs showed decreased cell growth and earlier cellular senescence with accumulation of p16 and p53, even though they expressed similar levels of CD105, CD90, and CD73 MSC marker proteins. GDM-UC-MSCs also displayed significantly lower osteogenic and adipogenic differentiation potentials than N-UC-MSCs. Furthermore, GDM-UC-MSCs exhibited a low mitochondrial activity and significantly reduced expression of the mitochondrial function regulatory genes ND2, ND9, COX1, PGC-1a, and TFAM. Here, we report intriguing and novel evidence that maternal metabolic derangement during gestation affects the biological properties of fetal cells, which may be a component of fetal programming. Our findings also underscore the importance of the critical assessment of the biological impact of maternal-fetal conditions in biological studies and clinical applications of hUC-MSCs.

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Section: Gdm-uc-mscs Undergo Premature Senescencementioning

confidence: 99%

Umbilical Cord Mesenchymal Stromal Cells Affected by Gestational Diabetes Mellitus Display Premature Aging and Mitochondrial Dysfunction

Kim

Piao

Pak

et al. 2015

Stem Cells and Development

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“…Recently, SA-α-Fuc has been identified as a novel marker of senescence that is upregulated in response to replicative, DNA damage-, and oncogene-induced senescence. Furthermore, as a marker of senescence, SA-α-Fuc is a more sensitive and robust biomarker for cell senescence when compared with SA-β-gal at the transcriptional and enzymatic levels (14).…”

Section: Markers Of Senescent Mscsmentioning

confidence: 99%

Senescence of mesenchymal stem cells (Review)

Wang

et al. 2017

International Journal of Molecular Medicine

209

187

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Mesenchymal stem cells (MSCs) have been used in cell-based therapy for various diseases, due to their immunomodulatory and inflammatory effects. However, the function of MSCs is known to decline with age, a process that is called senescence. To date, the process of MSC senescence remains unknown as in-depth understanding of the mechanisms involved in cellular senescence is lacking. First, senescent MSCs are so heterogeneous that not all of them express the same phenotypic markers. In addition, the genes and signaling pathways which regulate this process in MSCs are still unknown. Thus, an understanding of the molecular processes controlling MSC senescence is crucial to determining the drivers and effectors of age-associated MSC dysfunction. Moreover, the proper use of MSCs for clinical application requires a general understanding of the MSC aging process. Furthermore, such knowledge is essential for the development of therapeutic interventions that can slow or reverse age-related degenerative changes to enhance repair processes and maintain healthy function in aging tissues. To further clarify the properties of senescent cells, as well as to present significant findings from studies on the mechanisms of cellular aging, we summarize these biological features in the senescence of MSCs in this scenario. This review summarizes recent advances in our understanding of the markers and differentiation potential indicating MSC senescence, as well as factors affecting MSC senescence with particular emphasis on the roles of oxidative stress, intrinsic changes in telomere shortening, histone deacetylase and DNA methyltransferase, genes and signaling pathways and immunological properties.

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“…SA-β-Gal is a well-established marker for cellular aging, mainly known from dermatological studies. It represents the enzymatic level of cell senescence with expansion of the lysosomal compartment [43]. It is only expressed by senescent, not presenescent cells, e.g.…”

Section: Discussionmentioning

confidence: 99%

Idebenone Prevents Oxidative Stress, Cell Death and Senescence of Retinal Pigment Epithelium Cells by Stabilizing BAX/Bcl-2 Ratio

et al. 2015

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Purpose: Age-related macular degeneration (AMD) is one of the leading causes of blindness. Degeneration of the retinal pigment epithelium (RPE) is pathognomonic for the disease, and oxidative stress plays an important role in the pathogenesis of this disease. This study investigates potential antiapoptotic and cytoprotective effects of idebenone on cultured RPE cells (ARPE-19) under conditions of oxidative stress. Methods: ARPE-19 cells were treated with 1-100 µM idebenone. Cell viability (MTT assay), induction of intracellular reactive oxygen species (ROS) and histone-associated DNA fragments in mono- and oligonucleosomes, expression of proapoptotic BAX and antiapoptotic Bcl-2 as well as senescence-associated β-galactosidase (SA-β-Gal) activity were investigated under exposure to hydrogen peroxide (H₂O₂). Results: Idebenone concentrations from 1 to 20 µM showed no toxic effects on ARPE-19 cells. When cells were treated with H₂O₂, pretreatment with 5, 7.5, 10, and 20 µM idebenone led to a significant increase in the viability of ARPE-19 cells. In addition, idebenone pretreatment significantly attenuated the induction of SA-β-Gal and intracellular ROS as well as the amount of histone-associated DNA fragments after treatment with H₂O₂. The reduction of proapoptotic BAX and the elevation of antiapoptotic Bcl-2 under idebenone show that this process is rather mediated by inhibiting H₂O₂-induced apoptosis, not necrosis. Conclusion: In this study, idebenone increased survival of ARPE-19 cells and reduced cell death, senescence, and oxidative stress by stabilizing the BAX/Bcl-2 ratio.

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Senescence-associated lysosomalα-L-fucosidase (SA-α-Fuc): A sensitive and more robust biomarker for cellular senescence beyond SA-β-Gal

Cited by 22 publications

References 8 publications

Umbilical Cord Mesenchymal Stromal Cells Affected by Gestational Diabetes Mellitus Display Premature Aging and Mitochondrial Dysfunction

Umbilical Cord Mesenchymal Stromal Cells Affected by Gestational Diabetes Mellitus Display Premature Aging and Mitochondrial Dysfunction

Senescence of mesenchymal stem cells (Review)

Idebenone Prevents Oxidative Stress, Cell Death and Senescence of Retinal Pigment Epithelium Cells by Stabilizing BAX/Bcl-2 Ratio

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