Mathematical connection between short telomere induced senescence calculation and mortality rate data

Mapping Intimacies ◽

10.1101/2020.06.15.152348 ◽

2020 ◽

Author(s):

Jerry B. Torrance ◽

Steve Goldband

Keyword(s):

Mortality Rate ◽

Telomere Length ◽

Replicative Senescence ◽

Measurement Data ◽

Calculated Data ◽

Quantitative Agreement ◽

Scientific Activity ◽

Short Telomere ◽

Age Dependence ◽

Mathematical Connection

AbstractThe last 20 years have seen a surge in scientific activity and promising results in the study of aging and longevity. Many researchers have focused on telomeres, which are composed of a series of TTAGGG repeat nucleotide sequences at the ends of each chromosome. Measurements of the length of these telomere strands show that they decrease in length with increasing age, leading many authors to propose that when the length of these telomere strands decreases sufficiently, the cells enter into a state of replicative senescence, eventually leading to disease and death. These ideas are supported by evidence that short telomere length is correlated with increased mortality. In this paper, we extend this idea to make an actual calculation of the predicted mortality rate caused by short telomere length induced senescence (STLIS). We derive a simple equation for the mathematical relationship between telomere length and mortality rate. Using only 3 parameters based on telomere length measurement data of Canadians, we have calculated both the magnitude and the age dependence of the mortality rate, for both men and women. We show that these calculated data are in good quantitative agreement with the actual number of Canadians that die. This agreement provides strong evidence (but not proof) that the mechanism of STLIS plays an important role in the major diseases of aging (e.g., cardiovascular disease, many cancers, and diabetes mellitus) which dominate human mortality. This result represents significant progress in our understanding the factors behind the cause of aging.

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Mathematical Connection Between Short Telomere Induced Senescence Calculation and Mortality Rate Data

10.20944/preprints202007.0672.v1 ◽

2020 ◽

Author(s):

Jerry B. Torrance ◽

Steve Goldband

Keyword(s):

Mortality Rate ◽

Telomere Length ◽

Replicative Senescence ◽

Measurement Data ◽

Calculated Data ◽

Quantitative Agreement ◽

Scientific Activity ◽

Short Telomere ◽

Age Dependence ◽

Mathematical Connection

The last 20 years have seen a surge in scientific activity and promising results in the study of aging and longevity. Many researchers have focused on telomeres, which are composed of a series of TTAGGG repeat nucleotide sequences at the ends of each chromosome. Measurements of the length of these telomere strands show that they decrease in length with increasing age, leading many authors to propose that when the length of these telomere strands decreases sufficiently, the cells enter into a state of replicative senescence, eventually leading to disease and death. These ideas are supported by evidence that short telomere length is correlated with increased mortality. In this paper, we extend this idea to make an actual calculation of the predicted mortality rate caused by short telomere length induced senescence (STLIS). We derive a simple equation for the mathematical relationship between telomere length and mortality rate. Using only 3 parameters based on telomere length measurement data of Canadians, we have calculated both the magnitude and the age dependence of the mortality rate, for both men and women. We show that these calculated data are in good quantitative agreement with the actual number of Canadians that die. This agreement provides strong evidence (but not proof) that the mechanism of STLIS plays an important role in the major diseases of aging (e.g., cardiovascular disease, many cancers, and diabetes mellitus) which dominate human mortality. This result represents significant progress in our understanding the factors behind the cause of aging.

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Mathematical Connection between Short Telomere Induced Senescence Calculation and Mortality Rate Data

International Journal of Molecular Sciences ◽

10.3390/ijms21217959 ◽

2020 ◽

Vol 21 (21) ◽

pp. 7959

Author(s):

Jerry B. Torrance ◽

Steve Goldband

Keyword(s):

Mortality Rate ◽

Telomere Length ◽

Replicative Senescence ◽

Measurement Data ◽

Calculated Data ◽

Quantitative Agreement ◽

Scientific Activity ◽

Short Telomere ◽

Quantitative Correlation ◽

Mathematical Connection

The last 20 years have seen a surge in scientific activity and promising results in the study of aging and longevity. Many researchers have focused on telomeres, which are composed of a series of TTAGGG repeat nucleotide sequences at the ends of each chromosome. Measurements of the length of these telomere strands show that they decrease in length with increasing age, leading many authors to propose that when the length of these telomere strands decreases sufficiently, the cells enter into a state of replicative senescence, eventually leading to disease and death. These ideas are supported by evidence that short telomere length is correlated with increased mortality. In this paper, we extend this idea to make an actual calculation of the predicted mortality rate caused by short telomere length induced senescence (STLIS). We derive a simple equation for the mathematical relationship between telomere length and mortality rate. Using only three parameters based on telomere length measurement data of Canadians, we have calculated both the magnitude and the age dependence of the mortality rate for both men and women. We show that these calculated data are in good quantitative agreement with the actual number of Canadians that die. This agreement demonstrates the quantitative correlation between the mortality calculated by the STLIS model and the mortality of the major diseases of aging (e.g., cardiovascular disease, many cancers and diabetes mellitus), which dominate human mortality. This result represents significant progress in our understanding of the factors behind the cause of aging.

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Neutron dose evaluation of Elekta Linac at two energies (10 & 18 MV) by MCNP code and comparison with experimental measurements

JOURNAL OF ADVANCES IN PHYSICS ◽

10.24297/jap.v6i1.1820 ◽

2014 ◽

Vol 6 (1) ◽

pp. 1006-1015

Author(s):

Negin Shagholi ◽

Hassan Ali ◽

Mahdi Sadeghi ◽

Arjang Shahvar ◽

Hoda Darestani ◽

...

Keyword(s):

Monte Carlo ◽

Measurement Data ◽

Calculated Data ◽

High Energy ◽

Neutron Dose ◽

Dose Assessment ◽

Photon Flux ◽

Dose Equivalent ◽

Monte Carlo Techniques ◽

Neutron Dose Equivalent

Medical linear accelerators, besides the clinically high energy electron and photon beams, produce other secondary particles such as neutrons which escalate the delivered dose. In this study the neutron dose at 10 and 18MV Elekta linac was obtained by using TLD600 and TLD700 as well as Monte Carlo simulation. For neutron dose assessment in 2020 cm2 field, TLDs were calibrated at first. Gamma calibration was performed with 10 and 18 MV linac and neutron calibration was done with 241Am-Be neutron source. For simulation, MCNPX code was used then calculated neutron dose equivalent was compared with measurement data. Neutron dose equivalent at 18 MV was measured by using TLDs on the phantom surface and depths of 1, 2, 3.3, 4, 5 and 6 cm. Neutron dose at depths of less than 3.3cm was zero and maximized at the depth of 4 cm (44.39 mSvGy-1), whereas calculation resultedÂ in the maximum of 2.32 mSvGy-1 at the same depth. Neutron dose at 10 MV was measured by using TLDs on the phantom surface and depths of 1, 2, 2.5, 3.3, 4 and 5 cm. No photoneutron dose was observed at depths of less than 3.3cm and the maximum was at 4cm equal to 5.44mSvGy-1, however, the calculated data showed the maximum of 0.077mSvGy-1 at the same depth. The comparison between measured photo neutron dose and calculated data along the beam axis in different depths, shows that the measurement data were much more than the calculated data, so it seems that TLD600 and TLD700 pairs are not suitable dosimeters for neutron dosimetry in linac central axis due to high photon flux, whereas MCNPX Monte Carlo techniques still remain a valuable tool for photonuclear dose studies.

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Klotho genetic variants mediate the association between obstructive sleep apnea and short telomere length

Sleep Medicine ◽

10.1016/j.sleep.2021.01.015 ◽

2021 ◽

Author(s):

Priscila Farias Tempaku ◽

Vânia D’Almeida ◽

Sylvia Maria Affonso da Silva ◽

Monica Levy Andersen ◽

Sintia Iole Belangero ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Telomere Length ◽

Genetic Variants ◽

Short Telomere ◽

Obstructive Sleep

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Telomeres and replicative cellular aging of the human placenta and chorioamniotic membranes

Scientific Reports ◽

10.1038/s41598-021-84728-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tsung-Po Lai ◽

Mark Simpson ◽

Krunal Patel ◽

Simon Verhulst ◽

Jungsik Noh ◽

...

Keyword(s):

Dna Damage ◽

Preterm Birth ◽

Telomere Length ◽

Human Placenta ◽

Replicative Senescence ◽

Preterm Births ◽

Full Term ◽

Cellular Aging ◽

Telomere Dysfunction ◽

Replicative Aging

AbstractRecent hypotheses propose that the human placenta and chorioamniotic membranes (CAMs) experience telomere length (TL)-mediated senescence. These hypotheses are based on mean TL (mTL) measurements, but replicative senescence is triggered by short and dysfunctional telomeres, not mTL. We measured short telomeres by a vanguard method, the Telomere shortest length assay, and telomere-dysfunction-induced DNA damage foci (TIF) in placentas and CAMs between 18-week gestation and at full-term. Both the placenta and CAMs showed a buildup of short telomeres and TIFs, but not shortening of mTL from 18-weeks to full-term. In the placenta, TIFs correlated with short telomeres but not mTL. CAMs of preterm birth pregnancies with intra-amniotic infection showed shorter mTL and increased proportions of short telomeres. We conclude that the placenta and probably the CAMs undergo TL-mediated replicative aging. Further research is warranted whether TL-mediated replicative aging plays a role in all preterm births.

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Assessment of Long-Term in vitro Multiplied Human Wharton’s Jelly-Derived Mesenchymal Stem Cells prior to Their Use in Clinical Administration

Cells Tissues Organs ◽

10.1159/000517423 ◽

2021 ◽

pp. 1-11

Author(s):

Urvi Panwar ◽

Kanchan Mishra ◽

Parizad Patel ◽

Sumit Bharadva ◽

Salil Vaniawala ◽

...

Keyword(s):

Telomere Length ◽

Replicative Senescence ◽

Ex Vivo ◽

Wharton’S Jelly ◽

Cellular Aging ◽

Human Umbilical Cord ◽

Surface Markers ◽

Wharton's Jelly ◽

Ex Vivo Culture

The quantity of mesenchymal stem/stromal cells (MSCs) required for a particular therapy demands their subsequent expansion through ex vivo culture. During in vitro multiplication, they undergo replicative senescence which may alter their genetic stability. Therefore, this study was aimed to analyze cellular, molecular, and chromosomal alterations in Wharton’s jelly-derived MSCs (WJ-MSCs) during their in vitro sequential passages, where WJ-MSCs were sequentially passaged up to P14 and cells were evaluated at an interval of P2, P6, P10, and P14. They were examined for their morphology, tumorigenicity, surface markers, stemness markers, DNA damage, chromosomal aberration, and telomere length. We have processed five full-term delivered human umbilical cord samples to obtain WJ-MSCs. Morphological appearance observed at initial stages was small fine spindle-shaped WJ-MSCs which were transformed to flat, long, and broader cells in later passages. The cell proliferation rate was gradually decreased after the 10th passage. WJ-MSCs have expressed stemness markers OCT-4 and NANOG, while they showed high expression of positive surface markers CD90 and CD105 and lower expression of CD34 and CD45. They were non-tumorigenic with slow cellular aging during subsequent passages. There was no chromosomal abnormality up to the 14th passage, while increase in comet score and decrease in telomere length were observed in later passages. Hence, our study suggests that early and middle passaged (less than P10) WJ-MSCs are good candidates for clinical administration for treatment.

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Short telomere length in peripheral blood leukocytes in head and neck cancer: Findings in a Brazilian cohort

Head & Neck ◽

10.1002/hed.25472 ◽

2018 ◽

Vol 41 (3) ◽

pp. 672-677 ◽

Cited By ~ 1

Author(s):

Raquel M Alves-Paiva ◽

Fernanda Gutierrez-Rodrigues ◽

Diego A Pereira-Martins ◽

David Livingstone Alves Figueiredo ◽

Diego V Clé ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Telomere Length ◽

Neck Cancer ◽

Peripheral Blood ◽

Short Telomere ◽

Peripheral Blood Leukocytes ◽

Blood Leukocytes ◽

Brazilian Cohort

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Verification of modeling of convective events based on radar reflectivity

10.5194/egusphere-egu21-5224 ◽

2021 ◽

Author(s):

Ekaterina Svechnikova ◽

Nikolay Ilin ◽

Evgeny Mareev

Keyword(s):

General Pattern ◽

Measurement Data ◽

Quantitative Agreement ◽

Convective Event ◽

Simulation Results ◽

Verification Process ◽

Using Data ◽

Wrf Modeling ◽

Probabilistic Nature

The use of numerical modeling for atmospheric research is complicated by the problem of verification by a limited set of measurement data. Comparison with radar measurements is widely used for assessing the quality of the simulation. The probabilistic nature of the development of convective phenomena determines the complexity of the verification process: the reproduction of the pattern of the convective event is prior to the quantitative agreement of the values at a particular point at a particular moment.We propose a method for verifying the simulation results based on comparing areas with the same reflectivity. The method is applied for verification of WRF-modeling of convective events in the Aragats highland massif in Armenia. It is shown that numerical simulation demonstrates approximately the same form of distribution of areas of equal reflectivity as for radar-measured reflectivity. In this case, the model tends to overestimate on average reflectivity, while enabling us to obtain the qualitatively correct description of the convective phenomenon.The proposed technique can be used to verify the simulation results using data on reflectivity obtained by a satellite or a meteoradar. The technique allows one to avoid subjectivity in the interpretation of simulation results and estimate the quality of reproducing the &#8220;general pattern&#8221; of the convective event.

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Epigenetic features in regulation of telomeres and telomerase in stem cells

Emerging Topics in Life Sciences ◽

10.1042/etls20200344 ◽

2021 ◽

Author(s):

Fatma Dogan ◽

Nicholas R. Forsyth

Keyword(s):

Stem Cells ◽

Telomere Length ◽

Cell Biology ◽

Replicative Senescence ◽

Telomerase Activity ◽

Cell Phenotype ◽

Tissue Degeneration ◽

Unique System ◽

Telomerase Regulation

The epigenetic nature of telomeres is still controversial and different human cell lines might show diverse histone marks at telomeres. Epigenetic modifications regulate telomere length and telomerase activity that influence telomere structure and maintenance. Telomerase is responsible for telomere elongation and maintenance and is minimally composed of the catalytic protein component, telomerase reverse transcriptase (TERT) and template forming RNA component, telomerase RNA (TERC). TERT promoter mutations may underpin some telomerase activation but regulation of the gene is not completely understood due to the complex interplay of epigenetic, transcriptional, and posttranscriptional modifications. Pluripotent stem cells (PSCs) can maintain an indefinite, immortal, proliferation potential through their endogenous telomerase activity, maintenance of telomere length, and a bypass of replicative senescence in vitro. Differentiation of PSCs results in silencing of the TERT gene and an overall reversion to a mortal, somatic cell phenotype. The precise mechanisms for this controlled transcriptional silencing are complex. Promoter methylation has been suggested to be associated with epigenetic control of telomerase regulation which presents an important prospect for understanding cancer and stem cell biology. Control of down-regulation of telomerase during differentiation of PSCs provides a convenient model for the study of its endogenous regulation. Telomerase reactivation has the potential to reverse tissue degeneration, drive repair, and form a component of future tissue engineering strategies. Taken together it becomes clear that PSCs provide a unique system to understand telomerase regulation fully and drive this knowledge forward into aging and therapeutic application.

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