Molecular Biology

Aging (Aging-US)

Aging-US published this trending editorial on July 19, 2022 in Volume 14, Issue 14, entitled, "Restoring rhythm to prevent age-related fractures” by researchers Annelies E. Smit, Maaike Schilperoort, and Elizabeth M. Winter from the Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.

DOI - https://doi.org/10.18632/aging.204192 (PDF Download)

Corresponding author - Elizabeth M. Winter - e.m.winter@lumc.nl

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Keywords - aging, circadian rhythm, fractures, osteoporosis, glucocorticoids, chronotherapy

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at https://www.Aging-US.com​​ and connect with us:

SoundCloud - https://soundcloud.com/Aging-Us
Facebook - https://www.facebook.com/AgingUS/
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Trending With Impact: Restoring Rhythm to Prevent Age-related Fractures

Aging-US published this research paper on July 5, 2022 in Volume 14, Issue 14, entitled, "Common electrocardiogram measures are not associated with telomere length" by researchers Department of Cardiology, University Hospital, LMU Munich, Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute for Medical Information Processing, Biometry and Epidemiology, Medical Faculty, LMU Munich, Munich, Germany; Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, Mainz, Germany; Pettenkofer School of Public Health Munich, Institute for Medical Information Processing, Biometry and Epidemiology, Medical Faculty, LMU Munich, Munich, Germany.

DOI - https://doi.org/10.18632/aging.204149

Corresponding author - Moritz F. Sinner - moritz.sinner@med.uni-muenchen.de

Abstract

Aims: Aging is accompanied by telomere shortening. Increased telomere shortening is considered a marker of premature aging. Cardiac aging results in the development of cardiac pathologies. Electrocardiogram (ECG) measures reflect cardiac excitation, conduction, and repolarization. ECG measures also prolong with aging and are associated with cardiac pathologies including atrial fibrillation. As premature prolongation of ECG measures is observed, we hypothesized that such prolongation may be associated with telomere length.

Methods and Results: We studied the large, community-based KORA F4 Study. Of 3,080 participants enrolled between 2006 and 2007 with detailed information on demographic, anthropometric, clinical, and ECG characteristics, 2,575 presented with available data on leukocyte telomere length. Telomere length was determined by real-time quantitative PCR and expressed relative to a single copy gene. We fitted multivariable adjusted linear regression models to associate the ECG measures RR-interval, PR-interval, QRS-duration, and heart rate corrected QTc with telomere length.

In our cohort, the mean age was 54.9±12.9 years and 46.6% were men. Increased age was associated with shorter telomere length (p<0.01), and men had shorter telomere length than women (p<0.05). In unadjusted models, heart rate (p=0.023), PR-interval (p<0.01), and QTc-interval (p<0.01) were significantly associated with shorter telomere length. However, no significant associations remained after accounting for age, sex, and covariates.

Conclusions: ECG measures are age-dependent, but not associated with shortened telomere length as a marker of biological aging. Further research is warranted to clarify if shortened telomeres are associated with clinical cardiac pathologies including atrial fibrillation.

Keywords - aging, electrocardiogram, telomere length, cardiac aging

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at https://www.Aging-US.com​​ and connect with us:

SoundCloud - https://soundcloud.com/Aging-Us
Facebook - https://www.facebook.com/AgingUS/
Twitter - https://twitter.com/AgingJrnl
Instagram - https://www.instagram.com/agingjrnl/
YouTube - https://www.youtube.com/agingus​
LinkedIn - https://www.linkedin.com/company/aging/
Pinterest - https://www.pinterest.com/AgingUS/

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Paper Spotlight: Common ECG Measures are not Associated with Telomere Length

Oncotarget

Oncotarget published this priority research paper on August 3, 2022 in Volume 13, entitled, "A novel mechanism of regulation of the oncogenic transcription factor GLI3 by toll-like receptor signaling" by researchers from the Deparment of Molecular, Cellular and Biomedical Sciences, University of New Hampshire, Durham, NH; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX.

DOI - https://doi.org/10.18632/oncotarget.28261

Correspondence to - Sherine F. Elsawa - sherine.elsawa@unh.edu

Abstract

The transcription factor GLI3 is a member of the GLI family and has been shown to be regulated by canonical hedgehog (HH) signaling through smoothened (SMO). Little is known about SMO-independent regulation of GLI3. Here, we identify TLR signaling as a novel pathway regulating GLI3 expression. We show that GLI3 expression is induced by LPS/TLR4 in human monocyte cell lines and peripheral blood CD14+ cells. Further analysis identified TRIF, but not MyD88, signaling as the adapter used by TLR4 to regulate GLI3. Using pharmacological and genetic tools, we identified IRF3 as the transcription factor regulating GLI3 downstream of TRIF. Furthermore, using additional TLR ligands that signal through TRIF such as the TLR4 ligand, MPLA and the TLR3 ligand, Poly(I:C), we confirm the role of TRIF-IRF3 in the regulation of GLI3. We found that IRF3 directly binds to the GLI3 promoter region and this binding was increased upon stimulation of TRIF-IRF3 with Poly(I:C). Furthermore, using Irf3−/− MEFs, we found that Poly(I:C) stimulation no longer induced GLI3 expression. Finally, using macrophages from mice lacking Gli3 expression in myeloid cells (M-Gli3−/−), we found that in the absence of Gli3, LPS stimulated macrophages secrete less CCL2 and TNF-α compared with macrophages from wild-type (WT) mice. Taken together, these results identify a novel TLR-TRIF-IRF3 pathway that regulates the expression of GLI3 that regulates inflammatory cytokines and expands our understanding of the non-canonical signaling pathways involved in the regulation of GLI transcription factors.

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Keywords - GLI3, inflammation, TLR, cancer research

About Oncotarget

Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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Paper Spotlight: Novel Regulatory Mechanism of GLI3 by Toll-like Receptor Signaling

In the second installment of the Longevity & Aging Series, Dr. Steve Horvath revisits papers he co-authored that were published by Aging (Aging-US) and featured as a special collection of his research.

Special Collection - https://www.aging-us.com/special-collections-archive/steve-horvath
Author contact - Steve Horvath - shorvath@mednet.ucla.edu

Papers - 

DNA-methylation-based telomere length estimator: comparisons with measurements from flow FISH and qPCR
https://doi.org/10.18632/aging.203126

Epigenetic mutation load is weakly correlated with epigenetic age acceleration
https://doi.org/10.18632/aging.103950

Blood DNA methylation sites predict death risk in a longitudinal study of 12, 300 individuals
https://doi.org/10.18632/aging.103408

Epigenome-wide association study of leukocyte telomere length
https://doi.org/10.18632/aging.102230

DNA methylation-based estimator of telomere length
https://doi.org/10.18632/aging.102173

Optimism is not associated with two indicators of DNA methylation aging
https://doi.org/10.18632/aging.102090

Placental epigenetic clocks: estimating gestational age using placental DNA methylation levels
https://doi.org/10.18632/aging.102049

Rapamycin retards epigenetic ageing of keratinocytes independently of its effects on replicative senescence, proliferation and differentiation
https://doi.org/10.18632/aging.101976

Epigenetic clock analysis of human fibroblasts in vitro: effects of hypoxia, donor age, and expression of hTERT and SV40 largeT
https://doi.org/10.18632/aging.101955

DNA methylation GrimAge strongly predicts lifespan and healthspan
https://doi.org/10.18632/aging.101684

Cell and tissue type independent age-associated DNA methylation changes are not rare but common
https://doi.org/10.18632/aging.101666

A multi-tissue full lifespan epigenetic clock for mice
https://doi.org/10.18632/aging.101590

Epigenetic ageing is distinct from senescence-mediated ageing and is not prevented by telomerase expression
https://doi.org/10.18632/aging.101588

Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and ex vivo studies
https://doi.org/10.18632/aging.101508

An epigenetic biomarker of aging for lifespan and healthspan
https://doi.org/10.18632/aging.101414

Leukocyte telomere length, T cell composition and DNA methylation age
https://doi.org/10.18632/aging.101293

Accelerated epigenetic aging in Werner syndrome
https://doi.org/10.18632/aging.101217

An epigenetic aging clock for dogs and wolves
https://doi.org/10.18632/aging.101211

Longitudinal study of surrogate aging measures during human immunodeficiency virus seroconversion
https://doi.org/10.18632/aging.101184

Epigenetic clock analysis of diet, exercise, education, and lifestyle factors
https://doi.org/10.18632/aging.101168

Specific premature epigenetic aging of cartilage in osteoarthritis
https://doi.org/10.18632/aging.101053

DNA methylation-based measures of biological age: meta-analysis predicting time to death
https://doi.org/10.18632/aging.101020

Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels
https://doi.org/10.18632/aging.101005

Epigenetic age of the pre-frontal cortex is associated with neuritic plaques, amyloid load, and Alzheimer’s disease related cognitive functioning
https://doi.org/10.18632/aging.100864

Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring
https://doi.org/10.18632/aging.100861

Increased epigenetic age and granulocyte counts in the blood of Parkinson's disease patients
https://doi.org/10.18632/aging.100859

DNA methylation age of blood predicts future onset of lung cancer in the women's health initiative
https://doi.org/10.18632/aging.100809

Epigenetic age analysis of children who seem to evade aging
https://doi.org/10.18632/aging.100744

The cerebellum ages slowly according to the epigenetic clock
https://doi.org/10.18632/aging.100742

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at https://www.Aging-US.com​​ or connect with us:

SoundCloud - https://soundcloud.com/Aging-Us
Facebook - https://www.facebook.com/AgingUS/
Twitter - https://twitter.com/AgingJrnl
Instagram - https://www.instagram.com/agingjrnl/
YouTube - https://www.youtube.com/agingus​
LinkedIn - https://www.linkedin.com/company/aging/
Pinterest - https://www.pinterest.com/AgingUS/

Longevity & Aging Series (EP 2): Dr. Steve Horvath’s Special Collection in Aging

Mutant library

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Custom Viral Service

Aging-US published this trending research paper as the cover for Volume 14, Issue 14, entitled, "Aging the brain: multi-region methylation principal component based clock in the context of Alzheimer’s disease" by researchers from Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT; Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL; Department of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, CA; Department of Biostatistics, Fielding School of Public Health, UCLA, Los Angeles, CA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT; Alzheimer’s Disease Research Center, Yale University School of Medicine, New Haven, CT; VA Connecticut Healthcare System, West Haven, CT; Department of Pathology, Yale University School of Medicine, New Haven, CT; Altos Labs, San Diego Institute of Science, San Diego, CA.

DOI - https://doi.org/10.18632/aging.204196

Corresponding authors - Albert T. Higgins-Chen - a.higginschen@yale.edu, and Morgan E. Levine - morgan.levine@yale.edu

Abstract

Alzheimer’s disease (AD) risk increases exponentially with age and is associated with multiple molecular hallmarks of aging, one of which is epigenetic alterations. Epigenetic age predictors based on 5’ cytosine methylation (DNAm), or epigenetic clocks, have previously suggested that epigenetic age acceleration may occur in AD brain tissue. Epigenetic clocks are promising tools for the quantification of biological aging, yet we hypothesize that investigation of brain aging in AD will be assisted by the development of brain-specific epigenetic clocks. Therefore, we generated a novel age predictor termed PCBrainAge that was trained solely in cortical samples. This predictor utilizes a combination of principal components analysis and regularized regression, which reduces technical noise and greatly improves test-retest reliability. To characterize the scope of PCBrainAge’s utility, we generated DNAm data from multiple brain regions in a sample from the Religious Orders Study and Rush Memory and Aging Project. PCBrainAge captures meaningful heterogeneity of aging: Its acceleration demonstrates stronger associations with clinical AD dementia, pathologic AD, and APOE ε4 carrier status compared to extant epigenetic age predictors. It further does so across multiple cortical and subcortical regions. Overall, PCBrainAge’s increased reliability and specificity makes it a particularly promising tool for investigating heterogeneity in brain aging, as well as epigenetic alterations underlying AD risk and resilience.

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Press release - https://www.aging-us.com/news_room/aging-the-brain-multi-region-methylation-principal-component-based-clock-in-the-context-of-alzheimers-disease

Keywords - aging, epigenetic clocks, unsupervised machine learning, brain, Alzheimer’s, age acceleration

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at https://www.Aging-US.com​​ and connect with us:

SoundCloud - https://soundcloud.com/Aging-Us
Facebook - https://www.facebook.com/AgingUS/
Twitter - https://twitter.com/AgingJrnl
Instagram - https://www.instagram.com/agingjrnl/
YouTube - https://www.youtube.com/agingus​
LinkedIn - https://www.linkedin.com/company/aging/
Pinterest - https://www.pinterest.com/AgingUS/

Media Contact
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Trending With Impact: PCBrainAge in the Context of Alzheimer’s Disease

Dr. Cristina Aguayo-Mazzucato from Beta Cell Aging Lab, Joslin Diabetes Center, Harvard Medical School, discusses an editorial she co-authored that was published by Aging (Aging-US) in Volume 14, Issue 11, entitled, “Biological age in diabetes and precision medicine.”

DOI - https://doi.org/10.18632/aging.204123

Corresponding author - Cristina Aguayo-Mazzucato - cristina.aguayo-mazzucato@joslin.harvard.edu

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Keywords - biological age, diabetes mellitus, chronological age, DNA methylation, clinical biomarkers

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at http://www.Aging-US.com​​ or connect with us:

SoundCloud - https://soundcloud.com/Aging-Us
Facebook - https://www.facebook.com/AgingUS/
Twitter - https://twitter.com/AgingJrnl
Instagram - https://www.instagram.com/agingjrnl/
YouTube - https://www.youtube.com/agingus​
LinkedIn - https://www.linkedin.com/company/aging/
Pinterest - https://www.pinterest.com/AgingUS/

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Behind the Study: Biological Age in Diabetes and Precision Medicine

CD Genomics

RNA-Seq is the premier tool for mapping and quantifying transcriptomes by utilizing next-generation sequencing (NGS) technology. The transcriptome refers to the complete set of transcripts in a cell, which provides information on the transcript level for a specific developmental stage or physiological condition. Understanding the transcriptome is necessary for interpreting the functional elements of the genome and understanding development and disease. The key purpose of transcriptomics includes cataloging all species of transcripts; determining the transcriptional structure of genes; and quantifying the expression levels of each transcript under different conditions.

The Development and Workflow of RNA-seq, Learn more at https://www.cd-genomics.com/resourse-Bioinformatics-Workflow-of-RNA-Seq.html

Principle and Workflow of RNA Sequencing

Aging-US published this research paper on July 12, 2022 in Volume 14, Issue 13, entitled, "Age-related neuroendocrine, cognitive, and behavioral co-morbidities are promoted by HIV-1 Tat expression in male mice" by researchers from Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS; Department of Psychiatry, McLean Imaging Center, McLean Hospital/Harvard Medical School, Belmont, MA; Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS.

DOI - https://doi.org/10.18632/aging.204166

Corresponding author - Jason J. Paris - parisj@olemiss.edu

Abstract

In the U.S. about half of the HIV-infected individuals are aged 50 and older. In men living with HIV, secondary hypogonadism is common and occurs earlier than in seronegative men, and its prevalence increases with age. While the mechanisms(s) are unknown, the HIV-1 trans-activator of transcription (Tat) protein disrupts neuroendocrine function in mice partly by dysregulating mitochondria and neurosteroidogenesis. We hypothesized that conditional Tat expression in middle-aged male transgenic mice [Tat(+)] would promote age-related comorbidities compared to age-matched controls [Tat(−)]. We expected Tat to alter steroid hormone milieu consistent with behavioral deficits. Middle-aged Tat(+) mice had lower circulating testosterone and progesterone than age-matched controls and greater circulating corticosterone and central allopregnanolone than other groups. Young Tat(+) mice had greater circulating progesterone and estradiol-to-testosterone ratios. Older age or Tat exposure increased anxiety-like behavior (open field; elevated plus-maze), increased cognitive errors (radial arm water maze), and reduced grip strength. Young Tat(+), or middle-aged Tat(−), males had higher mechanical nociceptive thresholds than age-matched counterparts. Steroid levels correlated with behaviors. Thus, Tat may contribute to HIV-accelerated aging.

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Keywords - aging, hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-gonadal axis, secondary hypogonadism, trans-activating transcriptor

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at https://www.Aging-US.com​​ and connect with us:

SoundCloud - https://soundcloud.com/Aging-Us
Facebook - https://www.facebook.com/AgingUS/
Twitter - https://twitter.com/AgingJrnl
Instagram - https://www.instagram.com/agingjrnl/
YouTube - https://www.youtube.com/agingus​
LinkedIn - https://www.linkedin.com/company/aging/
Pinterest - https://www.pinterest.com/AgingUS/

Aging-US is published by Impact Journals, LLC: http://www.ImpactJournals.com​​

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