Interaction between ROS dependent DNA damage, mitochondria and p38 MAPK underlies senescence of human adult stem cells.

Abstract:

:Human endometrium-derived mesenchymal stem cells (hMESCs) enter the premature senescence under sublethal oxidative stress, however underlying mechanism remains unknown. Here, we showed that exogenous H2O2 induces a rapid phosphorylation and co-localization of ATM, H2A.X, 53BP1 leading to DNA damage response (DDR) activation. DDR was accompanied with nuclear translocation of p-p53 followed by up-regulation of p21Waf1 and the permanent hypophosphorylation of pRb. Additionally, the increased p38MAPK/MAPKAPK-2 activation persisted in H2O2-treated cells. We suggest that both p53/p21/pRb and p38MAPK/MAPKAPK-2 pathways are responsible for establishing an irreversible cell cycle arrest that is typical of senescence. The process of further stabilization of senescence required prolonged DDR signaling activation that was provided by the permanent ROS production which in turn was regulated by both p38MAPK and the increased functional mitochondria. To reverse senescence, the pharmacological inhibition of p38MAPK was performed. Cell treatment with SB203580 was sufficient to recover partially senescence phenotype, to block the ROS elevation, to decrease the mitochondrial function, and finally to rescue proliferation. Thus, suppression of the p38MAPK pathway resulted in a partial prevention of H2O2-induced senescence of hMESCs. The current study is the first to reveal the molecular mechanism of the premature senescence of hMESCs in response to oxidative stress.

journal_name

Aging (Albany NY)

journal_title

Aging

authors

Borodkina A,Shatrova A,Abushik P,Nikolsky N,Burova E

doi

10.18632/aging.100673

subject

Has Abstract

pub_date

2014-06-01 00:00:00

pages

481-95

issue

6

issn

1945-4589

pii

100673

journal_volume

6

pub_type

杂志文章

相关文献

Aging-US文献大全
  • NEAT1/miR-200b-3p/SMAD2 axis promotes progression of melanoma.

    abstract::Melanoma is a skin malignancy with a high mutation frequency of genetic alterations. MicroRNA (miR)-200b-3p is involved in various cancers, while in melanoma its bio-function remains unknown. In this study, we found that miR-200b-3p was down-regulated in melanoma tissues and cell lines compared to benign nevus cells. ...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.103909

    authors: Zhou WJ,Wang HY,Zhang J,Dai HY,Yao ZX,Zheng Z,Meng-Yan S,Wu K

    更新日期:2020-11-16 00:00:00

  • Impact of cardiovascular and metabolic diseases on the severity of COVID-19: a systematic review and meta-analysis.

    abstract::We examined the effects of coronary heart disease (CHD), hypertension and diabetes on the development of severe COVID-19. We performed a comprehensive, systematic literature search for studies published between December 2019 and July 5, 2020 in five databases. The prevalence of severe COVID-19 in patients with CHD, hy...

    journal_title:Aging

    pub_type: 杂志文章,meta分析

    doi:10.18632/aging.103991

    authors: Meng M,Zhao Q,Kumar R,Bai C,Deng Y,Wan B

    更新日期:2020-11-16 00:00:00

  • Immune-related biomarker risk score predicts prognosis in prostate cancer.

    abstract::In this study, we constructed a model using a Cox proportional hazards model based on the expression of eight immune-related genes that were associated with prognosis in prostate cancer: EDNRB, ANGPTL2, TNFSF15, TNFRSF10D, EDN2, BMP2, NLRP14, and PLK1. We then identified associations between risk scores calculated wit...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.103921

    authors: Liu Z,Zhong J,Cai C,Lu J,Wu W,Zeng G

    更新日期:2020-11-10 00:00:00

  • Colon cancer combined with obesity indicates improved survival- research on relevant mechanism.

    abstract::Obesity contributes to the incidence of various tumors, including colon cancer. However, the impact of obesity on patients' survival and related mechanisms remains unclear. Multi-omics data of 227 cases of colon cancer patients combined with clinical characteristics data were acquired from The Cancer Genome Atlas (TCG...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.103972

    authors: Yang Z,Wei X,Pan Y,Min Z,Xu J,Yu B

    更新日期:2020-11-10 00:00:00

  • N-acetyl-cysteine prevents age-related hearing loss and the progressive loss of inner hair cells in γ-glutamyl transferase 1 deficient mice.

    abstract::Genetic factors combined with oxidative stress are major determinants of age-related hearing loss (ARHL), one of the most prevalent disorders of the elderly. Dwarf grey mice, Ggt1dwg/dwg, are homozygous for a loss of function mutation of the g-glutamyl transferase 1 gene, which encodes an important antioxidant enzyme ...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.100927

    authors: Ding D,Jiang H,Chen GD,Longo-Guess C,Muthaiah VP,Tian C,Sheppard A,Salvi R,Johnson KR

    更新日期:2016-04-01 00:00:00

  • Hypothalamic ΔFosB prevents age-related metabolic decline and functions via SNS.

    abstract::The ventral hypothalamus (VHT) integrates several physiological cues to maintain glucose homeostasis and energy balance. Aging is associated with increased glucose intolerance but the underlying mechanisms responsible for age-related metabolic decline, including neuronal signaling in the VHT, remain elusive. We have s...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.101157

    authors: Sato K,Idelevich A,Nagano K,Rowe GC,Gori F,Baron R

    更新日期:2017-01-20 00:00:00

  • Association of KRAS and NRAS gene polymorphisms with Wilms tumor risk: a four-center case-control study.

    abstract::Wilms tumor is a type of pediatric solid tumor that arises partly due to somatic and germline mutations. Single-nucleotide polymorphisms (SNPs) in the RAS gene reportedly modify the risk for several types of human malignancies. We conducted a multicenter study to investigate whether RAS gene variants predispose indivi...

    journal_title:Aging

    pub_type: 杂志文章,多中心研究

    doi:10.18632/aging.101855

    authors: Fu W,Zhuo Z,Hua RX,Fu K,Jia W,Zhu J,Zhang J,Cheng J,Zhou H,Xia H,He J,Liu G

    更新日期:2019-03-12 00:00:00

  • Low circulating IGF-I bioactivity is associated with human longevity: findings in centenarians' offspring.

    abstract:UNLABELLED:Centenarians' offspring represent a suitable model to study age-dependent variables (e.g. IGF-I) potentially involved in the modulation of the lifespan. The aim of the present study was to investigate the role of the IGF-I in human longevity. We evaluated circulating IGF-I bioactivity measured by an innovati...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.100484

    authors: Vitale G,Brugts MP,Ogliari G,Castaldi D,Fatti LM,Varewijck AJ,Lamberts SW,Monti D,Bucci L,Cevenini E,Cavagnini F,Franceschi C,Hofland LJ,Mari D,Janssen J

    更新日期:2012-09-01 00:00:00

  • Telomere-dependent and telomere-independent origins of endogenous DNA damage in tumor cells.

    abstract::Human tumors and cultured cells contain elevated levels of endogenous DNA damage resulting from telomere dysfunction, replication and transcription errors, reactive oxygen species, and genome instability. However, the contribution of telomere-associated versus telomere-independent endogenous DNA lesions to this damage...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.100019

    authors: Nakamura AJ,Redon CE,Bonner WM,Sedelnikova OA

    更新日期:2009-02-04 00:00:00

  • LRP5 in age-related changes in vascular and alveolar morphogenesis in the lung.

    abstract::Aging is associated with impaired angiogenesis and lung alveolar regeneration, which contributes to the increased susceptibility to chronic lung diseases (CLD). We have reported that the Wnt ligand co-receptor, low-density lipoprotein receptor-related protein 5 (LRP5), stimulates angiogenesis and lung alveolar regener...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.101722

    authors: Mammoto A,Muyleart M,Mammoto T

    更新日期:2019-01-05 00:00:00

  • FAM84B, amplified in pancreatic ductal adenocarcinoma, promotes tumorigenesis through the Wnt/β-catenin pathway.

    abstract::Altered expression of family with sequence similarity 84, member B (FAM84B) has been found in various human cancers. However, the expression and function of FAM84B in pancreatic ductal adenocarcinoma (PDAC) has not been studied. Here, by analyzing The Cancer Genome Atlas cohort, we found that FAM84B amplification was ...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.103044

    authors: Zhang X,Xu J,Yan R,Zhang Y,Hu Z,Fu H,You Q,Cai Q,Yang D

    更新日期:2020-04-14 00:00:00

  • MSC-derived exosomes promote recovery from traumatic brain injury via microglia/macrophages in rat.

    abstract::Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in young individuals worldwide. There is currently no effective clinical treatment for TBI, but mesenchymal stem cell-derived exosomes have exhibited promising therapeutic effects. In this study, we performed intracerebroventricular microinject...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.103692

    authors: Chen Y,Li J,Ma B,Li N,Wang S,Sun Z,Xue C,Han Q,Wei J,Zhao RC

    更新日期:2020-09-23 00:00:00

  • Prognostic value of immune-related genes in clear cell renal cell carcinoma.

    abstract::Clear cell renal cell carcinoma (ccRCC) is the most common pathological subtype of renal cell carcinoma, and immune-related genes (IRGs) are key contributors to its development. In this study, the gene expression profiles and clinical data of ccRCC patients were downloaded from The Cancer Genome Atlas database and the...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.102548

    authors: Wan B,Liu B,Huang Y,Yu G,Lv C

    更新日期:2019-12-10 00:00:00

  • Melatonin alleviates meiotic defects in fetal mouse oocytes induced by Di (2-ethylhexyl) phthalate in vitro.

    abstract::Di (2-ethylhexyl) phthalate (DEHP), an estrogen-like compound that is a ubiquitous environmental contaminant, has been reported to adversely affect human and mammalian reproduction. Many studies have found that exposure to DEHP during pregnancy perturbs female germ cell meiosis and is detrimental to oogenesis. Previou...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.101715

    authors: Sun ZY,Zhang P,Wang JJ,Liu JC,Li L,Shen W,Zhai QY

    更新日期:2018-12-26 00:00:00

  • PKCζ-dependent upregulation of p27kip1 contributes to oxidative stress induced retinal pigment epithelial cell multinucleation.

    abstract::Retinal pigment epithelial (RPE) cells increase in size and multinucleate during aging. We have shown using human and mouse cell lines that oxidised photoreceptor outer segments (oxPOS)-induced cytokinesis failure is related to RPE cell multinucleation, although the underlying mechanism remains unknown. This study inv...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.101299

    authors: Rajapakse D,Chen M,Curtis TM,Xu H

    更新日期:2017-10-09 00:00:00

  • Accelerated aging syndromes, are they relevant to normal human aging?

    abstract::Hutchinson-Gilford Progeria (HGPS) and Werner syndromes are diseases that clinically resemble some aspects of accelerated aging. HGPS is caused by mutations in theLMNA gene resulting in post-translational processing defects that trigger Progeria in children. Werner syndrome, arising from mutations in the WRN helicase ...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.100383

    authors: Dreesen O,Stewart CL

    更新日期:2011-09-01 00:00:00

  • Pharmacological blockade of TNFα prevents sarcopenia and prolongs survival in aging mice.

    abstract::Sarcopenia is a hallmark of aging. Inflammation due to increased generation of cytokines such as TNFα, IL-1β and IL-6 has been implicated in the pathogenesis of sarcopenia. In skeletal muscle of C57BL/6 mice from 12 until 28 months of age, we observed a progressive reduction of myofiber cross sectional area, loss of t...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.202200

    authors: Sciorati C,Gamberale R,Monno A,Citterio L,Lanzani C,De Lorenzo R,Ramirez GA,Esposito A,Manunta P,Manfredi AA,Rovere-Querini P

    更新日期:2020-11-26 00:00:00

  • The role of commensal microbes in the lifespan of Drosophila melanogaster.

    abstract::Commensal microbes have mutualistic relationships with their host and mainly live in the host intestine. There are many studies on the relationships between commensal microbes and host physiology. However, there are inconsistent results on the effects of commensal microbes on host lifespan. To clarify this controversy...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.102073

    authors: Lee HY,Lee SH,Lee JH,Lee WJ,Min KJ

    更新日期:2019-07-12 00:00:00

  • Signatures of photo-aging and intrinsic aging in skin were revealed by transcriptome network analysis.

    abstract::There are various factors that alter physiological characteristics in skin. Elucidating the underlying mechanism of transcriptional alterations by intrinsic and extrinsic factors may lead us to understand the aging process of skin. To identify the transcriptomic changes of the aging skin, we analyzed publicly availabl...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.101496

    authors: Cho BA,Yoo SK,Seo JS

    更新日期:2018-07-18 00:00:00

  • PaCATB, a secreted catalase protecting Podospora anserina against exogenous oxidative stress.

    abstract::A differential mass spectrometry analysis of secreted proteins from juvenile and senescent Podospora anserina cultures revealed age-related differences in protein profiles. Among other proteins with decreased abundance in the secretome of senescent cultures a catalase, termed PaCATB, was identified. Genetic modulation...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.100360

    authors: Zintel S,Bernhardt D,Rogowska-Wrzesinska A,Osiewacz HD

    更新日期:2011-08-01 00:00:00

  • Aging dysregulates D- and E-series resolvins to modulate cardiosplenic and cardiorenal network following myocardial infarction.

    abstract::Post-myocardial infarction (MI), overactive inflammation is the hallmark of aging, however, the mechanism is unclear. We hypothesized that excess influx of omega 6 fatty acids may impair resolution, thus impacting the cardiosplenic and cardiorenal network post-MI. Young and aging mice were fed on standard lab chow (LC...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.101077

    authors: Halade GV,Kain V,Black LM,Prabhu SD,Ingle KA

    更新日期:2016-10-18 00:00:00

  • Brain ageing changes proteoglycan sulfation, rendering perineuronal nets more inhibitory.

    abstract::Chondroitin sulfate (CS) proteoglycans in perineuronal nets (PNNs) from the central nervous system (CNS) are involved in the control of plasticity and memory. Removing PNNs reactivates plasticity and restores memory in models of Alzheimer's disease and ageing. Their actions depend on the glycosaminoglycan (GAG) chains...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.101256

    authors: Foscarin S,Raha-Chowdhury R,Fawcett JW,Kwok JCF

    更新日期:2017-06-28 00:00:00

  • Aging augments the impact of influenza respiratory tract infection on mobility impairments, muscle-localized inflammation, and muscle atrophy.

    abstract::Although the influenza virus only infects the respiratory system, myalgias are commonly experienced during infection. In addition to a greater risk of hospitalization and death, older adults are more likely to develop disability following influenza infection; however, this relationship is understudied. We hypothesized...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.100882

    authors: Bartley JM,Pan SJ,Keilich SR,Hopkins JW,Al-Naggar IM,Kuchel GA,Haynes L

    更新日期:2016-04-01 00:00:00

  • Exosomal miR-183-5p promotes angiogenesis in colorectal cancer by regulation of FOXO1.

    abstract::Exosomes play important roles in proliferation and microenvironment modulation of many types of cancers, including colorectal cancer (CRC). However, the inhibitory effect of CRC cells-derived exosomes in angiogenesis has not been fully discussed. In this study, the roles of microRNA-183-5p (miR-183-5p) in abundant in ...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.103145

    authors: Shang A,Wang X,Gu C,Liu W,Sun J,Zeng B,Chen C,Ji P,Wu J,Quan W,Yao Y,Wang W,Sun Z,Li D

    更新日期:2020-05-03 00:00:00

  • Multiple dietary supplements do not affect metabolic and cardio-vascular health.

    abstract::Dietary supplements are widely used for health purposes. However, little is known about the metabolic and cardiovascular effects of combinations of popular over-the-counter supplements, each of which has been shown to have anti-oxidant, anti-inflammatory and pro-longevity properties in cell culture or animal studies. ...

    journal_title:Aging

    pub_type: 杂志文章,随机对照试验

    doi:10.18632/aging.100597

    authors: Soare A,Weiss EP,Holloszy JO,Fontana L

    更新日期:2014-02-01 00:00:00

  • Fighting the storm: could novel anti-TNFα and anti-IL-6 C. sativa cultivars tame cytokine storm in COVID-19?

    abstract::The main aspects of severe COVID-19 disease pathogenesis include hyper-induction of proinflammatory cytokines, also known as 'cytokine storm', that precedes acute respiratory distress syndrome (ARDS) and often leads to death. COVID-19 patients often suffer from lung fibrosis, a serious and untreatable condition. There...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.202500

    authors: Kovalchuk A,Wang B,Li D,Rodriguez-Juarez R,Ilnytskyy S,Kovalchuk I,Kovalchuk O

    更新日期:2021-01-19 00:00:00

  • Prevention of diet-induced hepatic steatosis and hepatic insulin resistance by second generation antisense oligonucleotides targeted to the longevity gene mIndy (Slc13a5).

    abstract::Reducing the expression of the Indy (I'm Not Dead Yet) gene in lower organisms extends life span by mechanisms resembling caloric restriction. Similarly, deletion of the mammalian homolog, mIndy (Slc13a5), encoding for a plasma membrane tricarboxylate transporter, protects from aging- and diet-induced adiposity and in...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.100854

    authors: Pesta DH,Perry RJ,Guebre-Egziabher F,Zhang D,Jurczak M,Fischer-Rosinsky A,Daniels MA,Willmes DM,Bhanot S,Bornstein SR,Knauf F,Samuel VT,Shulman GI,Birkenfeld AL

    更新日期:2015-12-01 00:00:00

  • Accelerated telomere shortening independent of LRRK2 variants in Chinese patients with Parkinson's disease.

    abstract::Oxidative stress and inflammation play vital roles in Parkinson's disease (PD) development. Thus, telomere length is expected to be shortened in this disease, but current data are inconclusive. We performed a case-control study of 261 patients with PD and 270 sex and age-matched healthy controls treated at the Peking ...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.103878

    authors: Wu Y,Pei Y,Yang Z,Li K,Lou X,Cui W

    更新日期:2020-10-29 00:00:00

  • Establishing a density-based method to separate proliferating and senescent cells from bone marrow stromal cells.

    abstract::To assist in the study of cellular aging, we established a new method of enriching physiologically aged bone marrow stromal cells (BMSCs) in animals of any age using a Percoll density gradient centrifugation technique. BMSCs from mice 2 months of age were isolated, and their cellular age determined (over 80% Scal-1+ C...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.103569

    authors: Xu F,Zhang Q,Wang H

    更新日期:2020-07-25 00:00:00

  • SLC7A2 serves as a potential biomarker and therapeutic target for ovarian cancer.

    abstract::The solute carrier (SLC) family is the largest group of membrane transporters, but their functions in ovarian cancer (OV) remain unclear. We analyzed SLC family members with amino acids-transporting functions in OV. The mRNA expression levels and prognostic values of SLCs in OV were analyzed in the Gene Expression Pro...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.103433

    authors: Sun T,Bi F,Liu Z,Yang Q

    更新日期:2020-07-09 00:00:00