scholarly journals Propagation of an Epigenetic Age-Related Disorder in Almond Is Governed by Vegetative Bud Ontogeny Rather Than Chimera-Type Cell Lineage

Horticulturae ◽  
2021 ◽  
Vol 7 (7) ◽  
pp. 190
Author(s):  
Thomas M. Gradziel ◽  
Kenneth A. Shackel
Keyword(s):  
Cell Fate ◽  
Cell Lineage ◽  
Prunus Dulcis ◽  
Axillary Buds ◽  
Related Disorder ◽  
Meristem Cell ◽  
Age Related ◽  
Epigenetic Aging ◽  
Epigenetic Age ◽  
Meristem Development

Almond (Prunus dulcis [Mill.] D.A. Webb) represents a model system for the study of epigenetic age-related disorders in perennial plants because the economically important noninfectious bud-failure disorder is well characterized and shown to be associated with the clonal-age of the propagation source. Epigenetic changes regulating disorders such as changes in methylation or telomere-length shortening would be expected to occur in shoot apical meristem initial cells since subsequent daughter cells including those in ensuing shoot axillary meristems show an irreversible advance in epigenetic aging. Because multiple initial cells are involved in meristem development and growth, such ‘mutations’ would be expected to occur in some initial cells but not others, resulting in mericlinal or sectorial chimeras during subsequent shoot development that, in turn, would differentially affect vegetative buds present in the leaf axils of the shoot. To test this developmental pattern, 2180 trees propagated from axillary buds of known position within asymptomatic noninfectious bud-failure budstick sources were evaluated for the disorder. Results demonstrate that relative bud position was not a determinant of successful trait propagation, but rather all axillary buds within individual shoots showed very similar degrees of noninfectious bud-failure. Control is thus more analogous to tissue-wide imprinting rather than being restricted to discrete cell lineages as would be predicted by standard meristem cell fate-mapping.

scholarly journals Propagation from Basal Epicormic Meristems Remediates an Aging-Related Disorder in Almond Clones

Horticulturae ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. 28 ◽  
Author(s):  
Gradziel ◽  
Lampinen ◽  
Preece
Keyword(s):  
Prunus Dulcis ◽  
Axillary Shoot ◽  
Alternative Source ◽  
Related Disorder ◽  
Asexual Propagation ◽  
Age Related ◽  
Nursery Practices ◽  
Commercially Important ◽  
Foundation Stock ◽  
Individual Trees

The asexual propagation of clonal crops has allowed cultivation of superior selections for thousands of years. With time, some clones deteriorate from genetic and epigenetic changes. Non-infectious bud-failure (NBF) in cultivated almond (Prunus dulcis) is a commercially important age-related disorder that results in the failure of new vegetative buds to grow in the spring, with dieback of terminal shoots, witches-brooming of surviving buds, and deformed bark (roughbark). The incidence of NBF increases with clone age, including within individual long-lived trees as well as nursery propagation lineages. It is not associated with any infectious disease agents. Consequently, nursery practices emphasize the establishment of foundation-mother blocks utilizing propagation-wood selected from proven and well-monitored propagation-lineages. Commercial propagation utilizes axillary shoot buds through traditional budding or grafting. This study examines NBF development using basal epicormic buds from individual trees of advanced age as an alternative source of foundation stock. Results show the age-related progression of NBF is suppressed in these epicormic meristems, possibly owing to their unique origins and ontogeny. NBF development in commercial orchards propagated from foundation blocks established from these sources was similarly dramatically suppressed even over the 10- to 20-year expected commercial orchard-life. Foundation-stock stability can be further maintained through appropriate management of propagation source-trees, which requires accurate knowledge of meristem origin and development.

scholarly journals Curculigoside Ameliorates Bone Loss by Influencing Mesenchymal Stem Cell Fate in Aging Mice

2021 ◽  
Vol 9 ◽  
Author(s):  
Na Wang ◽  
Ziyi Li ◽  
Shilun Li ◽  
Yukun Li ◽  
Liu Gao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Bone Loss ◽  
Cell Fate ◽  
Cell Lineage ◽  
Binding Motif ◽  
Osteoporosis Therapy ◽  
Senile Osteoporosis ◽  
Age Related

Senile osteoporosis is characterized by increased bone loss and fat accumulation in marrow. Curculigoside (CCG) is the major bioactive component of Curculigo orchioides, which has been used as anti-osteoporosis therapy for elder patients since antiquity. We aimed to investigate the underlying mechanisms by which CCG regulated the bone-fat balance in marrow of aging mice. In our study, CCG treatment was identified to interfere with the stem cell lineage commitment both in vivo and in vitro. In vivo, CCG promoted the transcriptional co-activator with PDZ-binding motif (TAZ) expression to reverse age-related bone loss and marrow adiposity. In vitro, proper concentration of CCG upregulated TAZ expression to increase osteogenesis and decrease adipogenesis of bone marrow mesenchymal stem cells (BMSCs). This regulating effect was discounted by TAZ knockdown or the use of MEK-ERK pathway inhibitor, UO126. Above all, our study confirmed the rescuing effects of CCG on the differential shift from adipogenesis to osteogenesis of BMSCs in aging mice and provided a scientific basis for the clinical use of CCG in senile osteoporosis.

scholarly journals The Epigenetic Pacemaker is a more sensitive tool than penalized regression for identifying moderators of epigenetic aging

2021 ◽  
Author(s):  
Colin Farrell ◽  
Kalsuda Lapborisuth ◽  
Chanyue Hu ◽  
Kyle Pu ◽  
Sagi Snir ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Penalized Regression ◽  
Chronological Age ◽  
Data Set ◽  
Epigenetic State ◽  
Age Related ◽  
Epigenetic Aging ◽  
Epigenetic Age ◽  
The Impact ◽  
The Relationship

Epigenetic clocks, DNA methylation based chronological age prediction models, are commonly employed to study age related biology. The error between the predicted and observed age is often interpreted as a form of biological age acceleration and many studies have measured the impact of environmental and other factors on epigenetic age. Epigenetic clocks are fit using approaches that minimize the error between the predicted and observed chronological age and as a result they reduce the impact of factors that may moderate the relationship between actual and epigenetic age. Here we compare the standard methods used to construct epigenetic clocks to an evolutionary framework of epigenetic aging, the epigenetic pacemaker (EPM) that directly models DNA methylation as a function of a time dependent epigenetic state. We show that the EPM is more sensitive than epigenetic clocks for the detection of factors that moderate the relationship between actual age and epigenetic state (ie epigenetic age). Specifically, we show that the EPM is more sensitive at detecting sex and cell type effects in a large aggregate data set and in an example case study is more sensitive sensitive at detecting age related methylation changes associated with polybrominated biphenyl exposure. Thus we find that the pacemaker provides a more robust framework for the study of factors that impact epigenetic age acceleration than traditional clocks based on linear regression models.

scholarly journals Telomere length and TERT expression are associated with age in almond (Prunus dulcis [Mill.] D.A.Webb)

2020 ◽  
Author(s):  
Katherine M. D’Amico-Willman ◽  
Elizabeth Anderson ◽  
Thomas M. Gradziel ◽  
Jonathan Fresnedo-Ramírez
Keyword(s):  
Telomere Length ◽  
Prunus Dulcis ◽  
Whole Genome Sequencing Data ◽  
Sequencing Data ◽  
Perennial Crop ◽  
Related Disorder ◽  
Age Cohorts ◽  
Perennial Plant ◽  
Biomarkers Of Aging ◽  
Age Related

AbstractWhile it is well known that all organisms age, our understanding of how aging occurs varies dramatically among species. The aging process in perennial plants is not well defined, yet can have implications on production and yield of valuable fruit and nut crops. Almond, a relevant nut crop, exhibits an age-related disorder known as non-infectious bud failure (BF) that affects vegetative bud development, indirectly affecting kernel-yield. This species and disorder present an opportunity to address aging in a commercially-relevant and vegetatively-propagated, perennial crop threatened by an aging-related disorder. In this study, we tested the hypothesis that telomere length and/or TERT expression can serve as biomarkers of aging in almond using both whole-genome sequencing data and leaf samples collected from distinct age cohorts over a two-year period. To measure telomere lengths, we employed both in silico and molecular approaches. We also measured expression of TERT, a subunit of the enzyme telomerase, which is responsible for maintaining telomere lengths. Results from this work show a marginal but significant association between both telomere length measured by monochrome multiplex quantitative PCR and TERT expression, and age of almond seedlings. These results suggest that as almonds age, TERT expression decreases and telomeres shorten. This work provides valuable information on potential biomarkers of perennial plant aging, contributing to our limited knowledge of this process. In addition, translation of this information will provide opportunities to address BF in almond breeding and nursery propagation.

scholarly journals Epigenetic Age Acceleration Reflects Long-Term Cardiovascular Health

2021 ◽  
Author(s):  
Brian Joyce ◽  
Tao Gao ◽  
Yinan Zheng ◽  
Jiantao Ma ◽  
Shih-Jen Hwang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Dna Methylation ◽  
Cardiovascular Health ◽  
Clinical Score ◽  
Chronological Age ◽  
Cvd Risk ◽  
Cross Sectional ◽  
Age Related ◽  
Epigenetic Aging ◽  
Epigenetic Age

Rationale: Epigenetic aging is a novel measure of biological age, reflecting exposures and disease risks independent of chronological age. It may serve as a useful biomarker of cardiovascular health (CVH) and/or cardiovascular disease (CVD) risk for early detection or prevention. Objective: To examine associations between GrimAge acceleration (GrimAA), a measure of epigenetic aging calculated from the residuals of GrimAge regressed on chronological age, and two repeated CVH measures: a full score for the AHA "Life's Simple 7" (diet, smoking, physical activity, BMI, blood pressure, total cholesterol, and glucose) and a clinical CVH score (BMI, blood pressure, cholesterol, and glucose). Methods and Results: We used Illumina array DNA methylation data from two prospective cohort studies: The Coronary Artery Risk Development in Young Adults (CARDIA) study and Framingham Heart Study (FHS), to calculate GrimAA and model associations with CVH. CARDIA randomly selected 1,118 participants for assays at Y15 (2000-2001; mean age 40) and/or Y20 (2005-2006); in FHS, 2,106 Offspring participants had DNA methylation measured at exam 8 (2005-2008; mean age 66). We examined multiple cross-sectional and longitudinal models of GrimAA and each CVH score measured at CARDIA Y0-Y20 and FHS exams 7-8. In CARDIA clinical CVH score from Y0-Y20 was associated with Y15 and Y20 GrimAA (β range -0.41 to -0.21 years per 1-point increase in CVH; p range <0.01 to 0.01), as was full score (β range -0.65 to -0.67 years; p<0.01 for all). These findings were validated in FHS (clinical score β range -0.51 to -0.54 years; full score β range -0.76 to -0.83 years; p<0.01 for all). Conclusions: Our data demonstrate that faster GrimAA is associated with the loss of CVH from young age. Epigenetic age may be a useful biomarker of CVD risk and provides biological insight into the role of epigenetic mechanisms linking age-related CVH loss and CVD.

scholarly journals Years of Schooling Could Reduce Epigenetic Aging: A Study of a Mexican Cohort

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1408
Author(s):  
Juan Carlos Gomez-Verjan ◽  
Marcelino Esparza-Aguilar ◽  
Verónica Martín-Martín ◽  
Cecilia Salazar-Perez ◽  
Cinthya Cadena-Trejo ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Low Income ◽  
Environmental Changes ◽  
P Value ◽  
Galactose Metabolism ◽  
Cholesterol Levels ◽  
Age Related ◽  
Epigenetic Aging ◽  
Epigenetic Age ◽  
Years Of Schooling

Adverse conditions in early life, including environmental, biological and social influences, are risk factors for ill-health during aging and the onset of age-related disorders. In this context, the recent field of social epigenetics offers a valuable method for establishing the relationships among them However, current clinical studies on environmental changes and lifespan disorders are limited. In this sense, the Tlaltizapan (Mexico) cohort, who 52 years ago was exposed to infant malnutrition, low income and poor hygiene conditions, represents a vital source for exploring such factors. Therefore, in the present study, 52 years later, we aimed to explore differences in clinical/biochemical/anthropometric and epigenetic (DNA methylation) variables between individuals from such a cohort, in comparison with an urban-raised sample. Interestingly, only cholesterol levels showed significant differences between the cohorts. On the other hand, individuals from the Tlaltizapan cohort with more years of schooling had a lower epigenetic age in the Horvath (p-value = 0.0225) and PhenoAge (p-value = 0.0353) clocks, compared to those with lower-level schooling. Our analysis indicates 12 differentially methylated sites associated with the PI3-Akt signaling pathway and galactose metabolism in individuals with different durations of schooling. In conclusion, our results suggest that longer durations of schooling could promote DNA methylation changes that may reduce epigenetic age; nevertheless, further studies are needed.

scholarly journals The aging DNA methylome reveals environment-by-aging interactions in a model teleost

2021 ◽  
Author(s):  
Emily M Bertucci ◽  
Marilyn W Mason ◽  
Olin E Rhodes ◽  
Benjamin B Parrott
Keyword(s):  
Dna Methylation ◽  
Environmental Factors ◽  
Environmental Drivers ◽  
Chronological Age ◽  
Epigenetic Clock ◽  
Ongoing Research ◽  
Dna Methylome ◽  
Age Related ◽  
Epigenetic Aging ◽  
Epigenetic Age

The rate at which individuals age underlies variation in life history and attendant health and disease trajectories. Age specific patterning of the DNA methylome (epigenetic aging) is strongly correlated with chronological age in humans and can be modeled to produce epigenetic age predictors. However, epigenetic age estimates vary among individuals of the same age, and this mismatch is correlated to the onset of age-related disease and all-cause mortality. Yet, the origins of epigenetic-to-chronological age discordance are not resolved. In an effort to develop a tractable model in which environmental drivers of epigenetic aging can be assessed, we investigate the relationship between aging and DNA methylation in a small teleost, medaka (Oryzias latipes). We find that age-associated DNA methylation patterning occurs broadly across the genome, with the majority of age-related changes occurring during early life. By modeling the stereotypical nature of age-associated DNA methylation dynamics, we built an epigenetic clock, which predicts chronological age with a mean error of 29.1 days (~4% of average lifespan). Characterization of clock loci suggests that aspects of epigenetic aging are functionally similar across vertebrates. To understand how environmental factors interact with epigenetic aging, we exposed medaka to four doses of ionizing radiation for seven weeks, hypothesizing that exposure to such an environmental stressor would accelerate epigenetic aging. While the epigenetic clock was not significantly affected, radiation exposure accelerated and decelerated patterns of normal epigenetic aging, with radiation-induced epigenetic alterations enriched at loci that become hypermethylated with age. Together, our findings advance ongoing research attempting to elucidate the functional role of DNA methylation in integrating environmental factors into the rate of biological aging.

scholarly journals Integrated analysis of the methylome and transcriptome of twin almonds (Prunus dulcis [Mill.] D.A.Webb) reveals genomic features associated with non-infectious bud failure

2021 ◽  
Author(s):  
Katherine M. D’Amico-Willman ◽  
Chad E. Niederhuth ◽  
Matthew R. Willman ◽  
Thomas M. Gradziel ◽  
Wilburforce Z. Ouma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Monozygotic Twin ◽  
Prunus Dulcis ◽  
Integrated Analysis ◽  
Related Disorder ◽  
Genomic Features ◽  
Genetic Components ◽  
Age Related ◽  
Genome Wide

I.SummaryAlmond (Prunus dulcis [Mill.] D.A.Webb) exhibits an age-related disorder called non-infectious bud-failure (BF) affecting vegetative bud development and nut yield. The underlying cause of BF remains unknown but is hypothesized to be associated with heritable epigenetic mechanisms. To address this disorder and its epigenetic components, we utilized a monozygotic twin study model profiling genome-wide DNA methylation and gene expression in two sets of twin almonds discordant for BF-exhibition. Analysis of DNA methylation patterns show that BF-exhibition and methylation, namely hypomethylation, are not independent phenomena. Transcriptomic data generated from the twin pairs also shows genome-wide differential gene expression associated with BF-exhibition. After identifying differentially methylated regions (DMRs) in each twin pair, a comparison revealed 170 shared DMRs between the two twin pairs. These DMRs and the associated genetic components may play a role in BF-exhibition. A subset of 52 shared DMRs are in close proximity to genes involved in meristem maintenance, cell cycle regulation, and response to heat stress. Annotation of specific genes included involvement in processes like cell wall development, calcium ion signaling, and DNA methylation. Results of this work support the hypothesis that BF-exhibition is associated with hypomethylation in almond, and identified DMRs and differentially expressed genes can serve as potential biomarkers to assess BF-potential in almond germplasm. Our results contribute to an understanding of the contribution of epigenetic disorders in agricultural performance and biological fitness of perennials.II.SignificanceThis study examines epigenetic components underlying noninfectious bud failure, an aging-related disorder affecting almond. Results from this work contribute to our understanding of the implications of DNA methylation on agricultural production, namely perennial fruit and nut production, due to effects on growth, development, and reproduction. Describing the methylome of discordant, monozygotic twin almonds enables the study of genomic features underlying noninfectious bud failure in this economically important crop.

scholarly journals EBF1 is expressed in pericytes and contributes to pericyte cell commitment

2021 ◽  
Author(s):  
Francesca Pagani ◽  
Elisa Tratta ◽  
Patrizia Dell’Era ◽  
Manuela Cominelli ◽  
Pietro Luigi Poliani
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
B Cell ◽  
Cell Fate ◽  
Early Stage ◽  
Cell Lineage ◽  
Cell Maturation ◽  
Cell Commitment

AbstractEarly B-cell factor-1 (EBF1) is a transcription factor with an important role in cell lineage specification and commitment during the early stage of cell maturation. Originally described during B-cell maturation, EBF1 was subsequently identified as a crucial molecule for proper cell fate commitment of mesenchymal stem cells into adipocytes, osteoblasts and muscle cells. In vessels, EBF1 expression and function have never been documented. Our data indicate that EBF1 is highly expressed in peri-endothelial cells in both tumor vessels and in physiological conditions. Immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and fluorescence-activated cell sorting (FACS) analysis suggest that EBF1-expressing peri-endothelial cells represent bona fide pericytes and selectively express well-recognized markers employed in the identification of the pericyte phenotype (SMA, PDGFRβ, CD146, NG2). This observation was also confirmed in vitro in human placenta-derived pericytes and in human brain vascular pericytes (HBVP). Of note, in accord with the key role of EBF1 in the cell lineage commitment of mesenchymal stem cells, EBF1-silenced HBVP cells showed a significant reduction in PDGFRβ and CD146, but not CD90, a marker mostly associated with a prominent mesenchymal phenotype. Moreover, the expression levels of VEGF, angiopoietin-1, NG2 and TGF-β, cytokines produced by pericytes during angiogenesis and linked to their differentiation and activation, were also significantly reduced. Overall, the data suggest a functional role of EBF1 in the cell fate commitment toward the pericyte phenotype.

scholarly journals Cellular Senescence in Lung Fibrosis

2021 ◽  
Vol 22 (13) ◽  
pp. 7012
Author(s):  
Fernanda Hernandez-Gonzalez ◽  
Rosa Faner ◽  
Mauricio Rojas ◽  
Alvar Agustí ◽  
Manuel Serrano ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cellular Senescence ◽  
Lung Fibrosis ◽  
Lung Diseases ◽  
Physiological Mechanism ◽  
Lung Parenchyma ◽  
Scar Tissue ◽  
Interstitial Lung Diseases ◽  
Cellular Damage ◽  
Age Related

Fibrosing interstitial lung diseases (ILDs) are chronic and ultimately fatal age-related lung diseases characterized by the progressive and irreversible accumulation of scar tissue in the lung parenchyma. Over the past years, significant progress has been made in our incomplete understanding of the pathobiology underlying fibrosing ILDs, in particular in relation to diverse age-related processes and cell perturbations that seem to lead to maladaptation to stress and susceptibility to lung fibrosis. Growing evidence suggests that a specific biological phenomenon known as cellular senescence plays an important role in the initiation and progression of pulmonary fibrosis. Cellular senescence is defined as a cell fate decision caused by the accumulation of unrepairable cellular damage and is characterized by an abundant pro-inflammatory and pro-fibrotic secretome. The senescence response has been widely recognized as a beneficial physiological mechanism during development and in tumour suppression. However, recent evidence strengthens the idea that it also drives degenerative processes such as lung fibrosis, most likely by promoting molecular and cellular changes in chronic fibrosing processes. Here, we review how cellular senescence may contribute to lung fibrosis pathobiology, and we highlight current and emerging therapeutic approaches to treat fibrosing ILDs by targeting cellular senescence.

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