Cell division and aging of the organism

Macieira‐Coelho, A.

doi:10.1007/s10522-011-9346-3

Cited by 21 publications

(13 citation statements)

References 102 publications

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“…Several recent review articles have discussed this subject . Although there are several cytometric methods to detect autophagy and lysosomal activity and, as mentioned, autophagy is of importance in aging and in discovery of gero‐suppressive agents , application of these methods in such studies is also not covered by the present review.…”

Section: Cytometric Analysis Of Cell Size and Heterogeneity A Potentmentioning

confidence: 97%

In search of antiaging modalities: Evaluation of mTOR‐ and ROS/DNA damage‐signaling by cytometry

et al. 2014

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This review presents the evidence in support of the IGF-1/mTOR/S6K1 signaling as the primary factor contributing to aging and cellular senescence. Reviewed are also specific interactions between mTOR/S6K1 and ROS-DNA damage signaling pathways. Outlined are critical sites along these pathways, including autophagy, as targets for potential antiaging (gero-suppressive) and/or chemopreventive agents. Presented are applications of flow- and laser scanning- cytometry utilizing phospho-specific Abs, to monitor activation along these pathways in response to the reported antiaging drugs rapamycin, metformin, berberine, resveratrol, vitamin D3, 2-deoxyglucose, and acetylsalicylic acid. Specifically, effectiveness of these agents to attenuate the level of constitutive mTOR signaling was tested by cytometry and confirmed by Western blotting through measuring phosphorylation of the mTOR-downstream targets including ribosomal protein S6. The ratiometric analysis of phosphorylated to total protein along the mTOR pathway offers a useful parameter reporting the effects of gero-suppressive agents. In parallel, their ability to suppress the level of constitutive DNA damage signaling induced by endogenous ROS was measured. While the primary target of each of these agents may be different the data obtained on several human cancer cell lines, WI-38 fibroblasts and normal lymphocytes suggest common downstream mechanism in which the decline in mTOR/S6K1 signaling and translation rate is coupled with a reduction of oxidative phosphorylation and ROS that leads to decreased oxidative DNA damage. The combined assessment of constitutive γH2AX expression, mitochondrial activity (ROS, ΔΨPm), and mTOR signaling provides an adequate gamut of cell responses to test effectiveness of gero-suppressive agents. Described is also an in vitro model of induction of cellular senescence by persistent replication stress, its quantitative analysis by laser scanning cytometry, and application to detect the property of the studied agents to attenuate the induction of senescence. Discussed is cytometric analysis of cell size and heterogeneity of size as a potential biomarker used to asses gero-suppressive agents and longevity.

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Section: Cytometric Analysis Of Cell Size and Heterogeneity A Potentmentioning

confidence: 97%

In search of antiaging modalities: Evaluation of mTOR‐ and ROS/DNA damage‐signaling by cytometry

et al. 2014

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“…The cumulative PD level (CPDL), which can be achieved by a specific cell type during serial passaging in vitro, depends upon several biological factors. These factors include the maximum lifespan of the species, developmental and adult age of the donor of the tissue biopsy, the site of the biopsy and the health status of the donor (Cristofalo et al, 2004;Macieira-Coelho, 2011). For example, for human fibroblasts the range of CPDL for the cell strains originating from embryonic tissues is between 50 and 70, whereas for those originating from adult biopsies it is generally less than 50 CPDL.…”

Section: Serial Subcultivation In Vitromentioning

confidence: 99%

Cell Senescence In Vitro

Rattan

2012

Encyclopedia of Life Sciences

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Cell senescence in vitro refers to the multitude of physiological, structural, biochemical and molecular changes that occur progressively during serial subcultivation of normal diploid cells, culminating in the permanent cessation of cell division. The whole duration of serial passaging is considered as the process of cellular ageing, and the end-stage irreversible growth arrest is termed as replicative senescence. The limited proliferative capacity of normal, diploid and differentiated cells is also known as the Hayflick limit, and the overall phenomenon is called the Hayflick phenomenon. A progressive loss of global deoxyribonucleic acid (DNA) methylation and of telomeres is considered to be the critical determinants of the Hayflick limit. However, in vivo, it is not the absolute number of senescent cells which is responsible for agerelated impairments, but it is the drift in cell functions occurring during repeated cell division that is relevant to ageing and age-related diseases. Cell senescence in the body is also considered to be a regulatory mechanism against cancer.

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“…Aged human corpus cavernosum also presented wider sinusoidal spaces, loss of muscle cell bundles, and increased connective tissue content [17]. The decrease in cell proliferation is a major manifestation of aging [21], and the mitotic index and the cell growth curve can be used to detect the cell proliferation [22].…”

Section: Discussionmentioning

confidence: 99%

Human Telomerase Reverse Transcriptase Transfection Reduces Apoptosis in Human Penile Smooth Muscle Cells and Slows Down Cellular Aging

Song

Zhang

et al. 2012

The Journal of Sexual Medicine

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Introduction Erectile dysfunction (ED) is one of the most common diseases in male urology that greatly affects the quality of life in senior people. Relaxation of corpus cavernosum smooth muscle is the key to penile erection. Aim To explore effects of human telomerase reverse transcriptase (hTERT) gene transfection on biological behaviors of human penile smooth muscle cells. Methods Human penile smooth muscle cells were grown in primary culture. A fluorescent eukaryotic expression vector, hTERT-internal ribosome entry site 2 (IRES2)-enhanced green fluorescent protein (EGFP), was constructed and transfected into human penile smooth muscle cells using Lipofectin reagent. Main Outcome Measure The telomerase activity, mitotic index, cell apoptosis, and cell growth curves of transfected smooth muscle cells were determined; the potential formation of malignant phenotypes in these transfected cells was investigated. Results Telomerase activity, mitotic index, and cell growth of hTERT-transfected cells were significantly higher than those of nontransfected cells and cells transfected with the empty EGFP vector, while apoptosis rates were the lowest in hTERT-transfected cells. No changes in cell morphology, chromosome number, and tumorigenicity were observed between hTERT-transfected cells and control cells. Conclusions In this study, for the first time, the hTERT gene was transfected into human penile smooth muscle cells, and the gene increased telomerase activity in cells, reduced cell apoptosis, and slowed down cell aging. We believe that this finding is of potential clinical value in the prevention and treatment of organic ED.

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Cell division and aging of the organism

Cited by 21 publications

References 102 publications

In search of antiaging modalities: Evaluation of mTOR‐ and ROS/DNA damage‐signaling by cytometry

In search of antiaging modalities: Evaluation of mTOR‐ and ROS/DNA damage‐signaling by cytometry

Cell Senescence In Vitro

Human Telomerase Reverse Transcriptase Transfection Reduces Apoptosis in Human Penile Smooth Muscle Cells and Slows Down Cellular Aging

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