Reversed Senescence of Retinal Pigment Epithelial Cell by Coculture With Embryonic Stem Cell via the TGFβ and PI3K Pathways

Wang, Shoubi; Liu, Yurun; Liu, Ying; Li, Chaoyang; Wan, Qi; Liu, Yang; Su, Yangfeng; Cheng, Yuanrong; Liu, Chang; Wang, Xiaoran; Wang, Zhichong

doi:10.3389/fcell.2020.588050

Cited by 15 publications

(9 citation statements)

References 51 publications

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“…Metabolomics analyses of AMD-derived RPE reveal aberrant metabolites of mitochondrial bioenergetics [ 24 ]. In senescent cells, including senescent RPE, altered mitochondrial metabolism and membrane potential promote inflammation via assorted pathways such as ROS and ATP production, DAMP (e.g., mtDNA) stimulation, and calcium exchange [ 141 – 144 ].…”

Section: Cellular Senescence Promotes Amd Through a Network Of Molecumentioning

confidence: 99%

Cellular senescence in the aging retina and developments of senotherapies for age-related macular degeneration

Lee

Lin

Copland

et al. 2021

J Neuroinflammation

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Age-related macular degeneration (AMD), a degenerative disease in the central macula area of the neuroretina and the supporting retinal pigment epithelium, is the most common cause of vision loss in the elderly. Although advances have been made, treatment to prevent the progressive degeneration is lacking. Besides the association of innate immune pathway genes with AMD susceptibility, environmental stress- and cellular senescence-induced alterations in pathways such as metabolic functions and inflammatory responses are also implicated in the pathophysiology of AMD. Cellular senescence is an adaptive cell process in response to noxious stimuli in both mitotic and postmitotic cells, activated by tumor suppressor proteins and prosecuted via an inflammatory secretome. In addition to physiological roles in embryogenesis and tissue regeneration, cellular senescence is augmented with age and contributes to a variety of age-related chronic conditions. Accumulation of senescent cells accompanied by an impairment in the immune-mediated elimination mechanisms results in increased frequency of senescent cells, termed “chronic” senescence. Age-associated senescent cells exhibit abnormal metabolism, increased generation of reactive oxygen species, and a heightened senescence-associated secretory phenotype that nurture a proinflammatory milieu detrimental to neighboring cells. Senescent changes in various retinal and choroidal tissue cells including the retinal pigment epithelium, microglia, neurons, and endothelial cells, contemporaneous with systemic immune aging in both innate and adaptive cells, have emerged as important contributors to the onset and development of AMD. The repertoire of senotherapeutic strategies such as senolytics, senomorphics, cell cycle regulation, and restoring cell homeostasis targeted both at tissue and systemic levels is expanding with the potential to treat a spectrum of age-related diseases, including AMD.

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Section: Cellular Senescence Promotes Amd Through a Network Of Molecumentioning

confidence: 99%

Cellular senescence in the aging retina and developments of senotherapies for age-related macular degeneration

Lee

Lin

Copland

et al. 2021

J Neuroinflammation

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“…In this work, fucoxanthin provided protection against hydrogen peroxide-induced ROS in human RPE cells. Sodium iodate- and hydrogen peroxide-induced ROS are well known for studying RPE cell senescence models [ 15 , 35 , 36 ]. Here, our results demonstrate that hydrogen peroxide can lead to cell senescence and increased ROS generation, MDA production and DNA damage in human RPE cells, but this process was substantially inhibited with fucoxanthin treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Aβ1-42, a component of drusen, contributes to inflammation, disturbed RPE morphology and function in AMD [ 14 ]. The strongest known risk factor for AMD is advanced age, with the risk of developing AMD with increasing senescence [ 15 ]. Other identified risk factors for AMD include oxidative stress, smoking, hypertension, hypercholesterolemia and diet [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Cytoprotective Potential of Fucoxanthin in Oxidative Stress-Induced Age-Related Macular Degeneration and Retinal Pigment Epithelial Cell Senescence In Vivo and In Vitro

et al. 2021

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Oxidative stress is identified as a major inducer of retinal pigment epithelium (RPE) cell dysregulation and is associated with age-related macular degeneration (AMD). The protection of RPE disorders plays an essential role in the pathological progress of retinal degeneration diseases. The pharmacological functions of fucoxanthin, a characteristic carotenoid, including anti-inflammatory and antioxidant properties, may ameliorate an outstanding bioactivity against premature senescence and cellular dysfunction. This study demonstrates that fucoxanthin protects RPE cells from oxidative stress-induced premature senescence and decreased photoreceptor cell loss in a sodium iodate-induced AMD animal model. Similarly, oxidative stress induced by hydrogen peroxide, nuclear phosphorylated histone (γH2AX) deposition and premature senescence-associated β-galactosidase staining were inhibited by fucoxanthin pretreatment in a human RPE cell line, ARPE-19 cells. Results reveal that fucoxanthin treatment significantly inhibited reactive oxygen species (ROS) generation, reduced malondialdehyde (MDA) concentrations and increased the mitochondrial metabolic rate in oxidative stress-induced RPE cell damage. Moreover, atrophy of apical microvilli was inhibited in cells treated with fucoxanthin after oxidative stress. During aging, the RPE undergoes well-characterized pathological changes, including amyloid beta (Aβ) deposition, beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) expression and tight junction disruption, which were also reduced in fucoxanthin-treated groups by immunofluorescence. Altogether, pretreatment with fucoxanthin may protect against premature senescence and cellular dysfunction in retinal cells by oxidative stress in experimental AMD animal and human RPE cell models.

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“…Therefore, we explore the anti-aging effect of LMV on the bone from aged rats. SA-β-Gal was a method which many studies had used to verify the senescence reversal [ 32 – 34 ]. In our study, we used SA-β-Gal to verify reversal effect of LMV on osteogenic cell senescence.…”

Section: Discussionmentioning

confidence: 99%

Low magnitude vibration alleviates age-related bone loss by inhibiting cell senescence of osteogenic cells in naturally senescent rats

Wen

Bao

Tang

et al. 2021

Aging

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Dysfunction of bone marrow mesenchymal stem cells (BMSCs), osteoblasts and osteocytes may be one of the main causes of bone loss in the elderly. In the present study, we found osteogenic cells from aged rats all exhibited senescence changes, with the most pronounced senescence changes in osteocytes. Meanwhile, the proliferative capacity and functional activity of osteogenic cells from aged rats were suppressed. Osteogenic differentiation capacity of BMSCs from aged rats decreased while adipogenic capacity increased. The mineralization capacity, ALP activity and osteogenic proteins expression of osteoblasts from aged rats decreased. Additionally, osteocytes from aged rats up-expressed sclerosteosis protein, a negative regulator of bone formation. To inhibit osteogenic cell senescence, we use low magnitude vibration (LMV) to eliminate the senescent osteogenic cells. After LMV treatment, the number of osteogenic cells staining positively for senescence-associated-β-galactosidase (SA-β-Gal) decreased significantly. Besides, the expression of anti-aging protein SIRT1 was upregulated significantly, while p53 and p21 were downregulated significantly after LMV treatment. Thus, the LMV can inhibit the senescence of osteogenic cells partly through the Sirt1/p53/p21 axis. Furthermore, LMV was found to promote bone formation of aged rats. These results suggest that the inhibition of osteogenic cell senescence by LMV is a valuable treatment to prevent or delay osteoporosis.

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Reversed Senescence of Retinal Pigment Epithelial Cell by Coculture With Embryonic Stem Cell via the TGFβ and PI3K Pathways

Cited by 15 publications

References 51 publications

Cellular senescence in the aging retina and developments of senotherapies for age-related macular degeneration

Cellular senescence in the aging retina and developments of senotherapies for age-related macular degeneration

Cytoprotective Potential of Fucoxanthin in Oxidative Stress-Induced Age-Related Macular Degeneration and Retinal Pigment Epithelial Cell Senescence In Vivo and In Vitro

Low magnitude vibration alleviates age-related bone loss by inhibiting cell senescence of osteogenic cells in naturally senescent rats

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