Search results for "SENESCENCE"

O101 : Histone variant macroH2A1 orchestrates escape from hepatocyte senescence during ageing and cancer

2015

Changes associated with aging and replicative senescence in the regulation of transcription factor nuclear factor-kappa B.

1996

Both the aging of animals and the senescence of cultured cells involve an altered pattern of gene expression, suggesting changes in transcription factor regulation. We studied age-related changes in transcription factors nuclear factor (NF)-kappa B, activator protein factor-1 (AP-1) and Sp-1 by using electrophoretic mobility shift binding assays; we also analysed changes in the protein components of NF-kappa B complex with Western blot assays. Nuclear and cytoplasmic extracts were prepared from heart, liver, kidney and brain of young adult and old NMRI mice and Wistar rats as well as from presenescent, senescent and simian virus 40-immortalized human WI-38 fibroblasts. Aging of both mice an…

Regulation of the p19(Arf)/p53 pathway by histone acetylation underlies neural stem cell behavior in senescence-prone SAMP8 mice.

2015

Brain aging is associated with increased neurodegeneration and reduced neurogenesis. B1/neural stem cells (B1-NSCs) of the mouse subependymal zone (SEZ) support the ongoing production of olfactory bulb interneurons, but their neurogenic potential is progressively reduced as mice age. Although age-related changes in B1-NSCs may result from increased expression of tumor suppressor proteins, accumulation of DNA damage, metabolic alterations, and microenvironmental or systemic changes, the ultimate causes remain unclear. Senescence-accelerated-prone mice (SAMP8) relative to senescence-accelerated-resistant mice (SAMR1) exhibit signs of hastened senescence and can be used as a model for the stud…

Synthetic lethal metabolic targeting of cellular senescence in cancer therapy.

2013

Activated oncogenes and anticancer chemotherapy induce cellular senescence, a terminal growth arrest of viable cells characterized by S-phase entry-blocking histone 3 lysine 9 trimethylation (H3K9me3). Although therapy-induced senescence (TIS) improves long-term outcomes, potentially harmful properties of senescent tumour cells make their quantitative elimination a therapeutic priority. Here we use the Eµ-myc transgenic mouse lymphoma model in which TIS depends on the H3K9 histone methyltransferase Suv39h1 to show the mechanism and therapeutic exploitation of senescence-related metabolic reprogramming in vitro and in vivo. After senescence-inducing chemotherapy, TIS-competent lymphomas but …

Long-term effects of delayed parenthood.

1998

The present study aims to define, characterize and compare the long-term effects on offspring of delayed parenthood. Data published so far on this topic show that maternal and paternal ageing may affect offspring by different mechanisms. Delayed motherhood is characterized by increased probability of obstetric complications and/or fetal and perinatal problems which, in turn, may increase the risks of mortality and morbidity in newborns and later life. Furthermore, maternal ageing is distinguished by a decreased ratio of male to female infants and higher odds of conceiving a trisomic child and/or an individual suffering from mitochondrial DNA disorders. In contrast, delayed fatherhood is ass…

Effects of strength training on muscle power and serum hormones in middle-aged and older men.

2001

Effects of 16-wk strength training on maximal strength and power performance of the arm and leg muscles and serum concentrations [testosterone (T), free testosterone (FT), and cortisol] were examined in 11 middle-aged (M46; 46 ± 2 yr) and 11 older men (M64; 64 ± 2 yr). During the 16-wk training, the relative increases in maximal strength and muscle power output of the arm and leg muscles were significant in both groups ( P < 0.05–0.001), with no significant differences between the two groups. The absolute increases were higher ( P < 0.01–0.05) in M46 than in M64 mainly during the last 8 wk of training. No significant changes were observed for serum T and FT concentrations. Analysis o…

Age-related changes in the regulation of transcription factor NF-kappa B in rat brain.

1997

Aging process involves an increase in stress at cellular level. We studied whether aging affects the regulation of stress responsive transcription factor NF-kappa B in brain samples of Wistar rats. Hippocampus, cerebellum, and temporal and frontal lobes of cortex were studied. We observed a significant up-regulation in the constitutive, nucleus-located NF-kappa B binding activity in 30-month-old Wistar rats compared to young and 18-month-old rats. The increase was most prominent in cerebellum and in frontal cortex, but age-related changes did not occur in hippocampus. Inducible, cytoplasmic NF-kappa B binding activity was not affected by aging in any of the samples studied. Western blot ass…

The importance of culturing primary cells under physiological conditions: proliferation, senescence, pluripotency

2017

Mesenchymal stem cells (MSCs), such as human dental pulp stem cells (hDPSCs), are currently a source for cell therapy. However, cell therapy protocols require 10–400 million cells per treatment, and consequently, they need to be expanded in vitro before implantation, with the inconvenience that MSCs undergo senescence following a certain number of cell expansion passages, loosing their stem cell qualities. Ambient oxygen tension (21% pO2) is normally used for in vitro culture, but physiological levels in vivo range between 3% and 6% pO2. We previously demonstrated that hDPSC proliferation rate is significantly lowered at 21% pO2 due to enhanced oxidative stress, which led to the activation …

Network Pharmacology of Ginseng (Part II): The Differential Effects of Red Ginseng and Ginsenoside Rg5 in Cancer and Heart Diseases as Determined by …

2021

Panax ginseng C.A.Mey. is an adaptogenic plant traditionally used to enhance mental and physical capacities in cases of weakness, exhaustion, tiredness, or loss of concentration, and during recovery. According to ancient records, red ginseng root preparations enhance longevity with long-term intake. Recent pharmacokinetic studies of ginsenosides in humans and our in vitro study in neuronal cells suggest that ginsenosides are effective when their levels in blood is low—at concentrations from 10−6 to 10−18 M. In the present study, we compared the effects of red ginseng root preparation HRG80TM(HRG) at concentrations from 0.01 to 10,000 ng/mL with effects of white ginseng (WG) and purified gin…

The role of mitochondrial oxidative stress in aging.

2003

Mitochondria are both a major source of oxidants and a target for their damaging effects, and, therefore, mitochondrial oxidative stress appears to be a cause, rather than a consequence, of cell aging. Oxidative damage in aging is particularly high in specific molecular targets, such as mitochondrial DNA and aconitase, and mitochondrial oxidative stress may drive tissue aging through intrinsic apoptosis. Mitochondrial function and morphology are impaired upon aging, as judged by a decline in membrane potential as well as by an increase in peroxide production and size of the organelles. In view of the age-related decreases in mitochondrial protein synthesis, mitochondrial transcripts, and ex…