Genomics

Aging (Aging-US)

Aging (Aging-US) published this priority research paper as the cover for Volume 14, Issue 1, entitled, "Reduced growth rate of aged muscle stem cells is associated with impaired mechanosensitivity" by researchers from the Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam 1081 HZ, The Netherlands; Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam 1081 LA, The Netherlands; Sorbonne Université, INSERM UMRS974, Center for Research in Myology, Paris 75013, France; Department of Physiology, Amsterdam University Medical Center VUmc, Amsterdam Cardiovascular Sciences, Amsterdam 1081 HZ, The Netherlands; Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve 1348, Belgium; Exercise Physiology Research Group, Department of Movement Sciences, KU Leuven, Leuven 3001, Belgium; Faculty of Medicine and Pharmacy, NeuroMyoGène UCBL-CNRS UMR 5310, INSERM U1217, Lyon 69008, France.

DOI - https://doi.org/10.18632/aging.203830

Correspondence to - Richard T. Jaspers - r.t.jaspers@vu.nl

Abstract:
Aging-associated muscle wasting and impaired regeneration are caused by deficiencies in muscle stem cell (MuSC) number and function. We postulated that aged MuSCs are intrinsically impaired in their responsiveness to omnipresent mechanical cues through alterations in MuSC morphology, mechanical properties, and number of integrins, culminating in impaired proliferative capacity. Here we show that aged MuSCs exhibited significantly lower growth rate and reduced integrin-α7 expression as well as lower number of phospho-paxillin clusters than young MuSCs. Moreover, aged MuSCs were less firmly attached to matrigel-coated glass substrates compared to young MuSCs, as 43% of the cells detached in response to pulsating fluid shear stress (1 Pa). YAP nuclear localization was 59% higher than in young MuSCs, yet YAP target genes Cyr61 and Ctgf were substantially downregulated. When subjected to pulsating fluid shear stress, aged MuSCs exhibited reduced upregulation of proliferation-related genes. Together these results indicate that aged MuSCs exhibit impaired mechanosensitivity and growth potential, accompanied by altered morphology and mechanical properties as well as reduced integrin-α7 expression. Aging-associated impaired muscle regenerative capacity and muscle wasting is likely due to aging-induced intrinsic MuSC alterations and dysfunctional mechanosensitivity.

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Keywords - aging, mechanosensitivity, muscle stem cell, proliferation, YAP signaling

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/

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

Media Contact
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MEDIA@IMPACTJOURNALS.COM

Impaired Mechanosensitivity in Aged Muscle Stem Cells

Aging (Aging-US) published this research paper in Volume 11, Issue 18, entitled, "Inadequate control of thyroid hormones sensitizes to hepatocarcinogenesis and unhealthy aging" by researchers from the Department of Regeneration and Cell Therapy, Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, Seville, Spain; Instituto de la Grasa (CSIC), Universidad Pablo de Olavide, Sevilla, Spain; Centro de Investigación Príncipe Felipe, Valencia, Spain; Department of Human Physiology, Málaga University, Biomedical Research Institute of Málaga (IBIMA), Málaga, Spain; Instituto de Investigación Biomédica de Málaga-IBIMA, UGC Endocrinología y Nutrición. Hospital Regional Universitario de Málaga, Málaga, Spain; Biomedical Research Network on Diabetes and Related Metabolic Diseases-CIBERDEM, Instituto de Salud Carlos III, Madrid, Spain; Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide and CIBERER, Sevilla, Spain; Department of Physiology, University Miguel Hernández School of Medicine Sant Joan d'Alacant, Alicante, Spain.

DOI - https://doi.org/10.18632/aging.102285

Correspondence to - Alejandro Martin-Montalvo - alejandro.martinmontalvo@cabimer.es and Benoit Raymond Gauthier - benoit.gauthier@cabimer.es

Abstract:
An inverse correlation between thyroid hormone levels and longevity has been reported in several species and reduced thyroid hormone levels have been proposed as a biomarker for healthy aging and metabolic fitness. However, hypothyroidism is a medical condition associated with compromised health and reduced life expectancy. Herein, we show, using wild-type and the Pax8 ablated model of hypothyroidism in mice, that hyperthyroidism and severe hypothyroidism are associated with an overall unhealthy status and shorter lifespan. Mild hypothyroid Pax8 +/- mice were heavier and displayed insulin resistance, hepatic steatosis and increased prevalence of liver cancer yet had normal lifespan. These pathophysiological conditions were precipitated by hepatic mitochondrial dysfunction and oxidative damage accumulation. These findings indicate that individuals carrying mutations on PAX8 may be susceptible to develop liver cancer and/or diabetes and raise concerns regarding the development of interventions aiming to modulate thyroid hormones to promote healthy aging or lifespan in mammals.

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Press release - https://www.aging-us.com/news_room/inadequate-control-of-thyroid-hormones-sensitizes-to-hepatocarcinogenesis-and-unhealthy-aging

Keywords - lifespan, healthspan, thyroid hormones, hyperthyroidism, hypothyroidism, glucose metabolism

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/

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

Media Contact
18009220957
MEDIA@IMPACTJOURNALS.COM

Paper Spotlight: Modulation of Thyroid Hormones Leads to Unhealthy Aging

Aging (Aging-US) published this trending research paper in Volume 11, Issue 24, entitled, "Age-related changes in eye lens biomechanics, morphology, refractive index and transparency" by researchers from the School of Optometry, Indiana University, Bloomington, IN; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA; Department of Biological Sciences, University of Delaware, Newark, DE; Department of Neurobiology, Morehouse School of Medicine, Atlanta, GA; School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom; Japan Synchrotron Radiation Research Institute (Spring-8), Sayo-cho, Sayo-gun, Hyogo, Japan; Department of Radiology, Boston University School of Medicine, Boston, MA.

Abstract:
Life-long eye lens function requires an appropriate gradient refractive index, biomechanical integrity and transparency. We conducted an extensive study of wild-type mouse lenses 1-30 months of age to define common age-related changes. Biomechanical testing and morphometrics revealed an increase in lens volume and stiffness with age. Lens capsule thickness and peripheral fiber cell widths increased between 2 to 4 months of age but not further, and thus, cannot account for significant age-dependent increases in lens stiffness after 4 months. In lenses from mice older than 12 months, we routinely observed cataracts due to changes in cell structure, with anterior cataracts due to incomplete suture closure and a cortical ring cataract corresponding to a zone of compaction in cortical lens fiber cells. Refractive index measurements showed a rapid growth in peak refractive index between 1 to 6 months of age, and the area of highest refractive index is correlated with increases in lens nucleus size with age. These data provide a comprehensive overview of age-related changes in murine lenses, including lens size, stiffness, nuclear fraction, refractive index, transparency, capsule thickness and cell structure. Our results suggest similarities between murine and primate lenses and provide a baseline for future lens aging studies.

Special collection on eye disease - https://www.aging-us.com/special-collections-archive/eye-disease

Press release - https://www.aging-us.com/news_room/age-related-changes-in-eye-lens-biomechanics

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DOI - https://doi.org/10.18632/aging.102584

Full text - https://www.aging-us.com/article/102584/text

Correspondence to: Velia M. Fowler email: vfowler@udel.edu and Catherine Cheng email: ckcheng@iu.edu

Keywords: fiber cell, strain, epithelial cell, cataract, stiffness

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 on:

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 please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls

Media Contact
18009220957
MEDIA@IMPACTJOURNALS.COM

Paper Spotlight: Common Age-related Changes in Eye Lens Function

Copy: Aging-US published this research paper as the cover for Volume 13, Issue 24, entitled, “Age-dependent expression changes of circadian system-related genes reveal a potentially conserved link to aging” by researchers from Bioinformatics/High Throughput Analysis, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena, Jena, Germany; FLI Leibniz Institute for Age Research, Jena, Germany; Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany; German Center for Integrative Biodiversity Research (iDiv), Halle-Jena-Leipzig, Germany; European Virus Bioinformatics Center (EVBC), Jena, Germany.

Abstract
The circadian clock system influences the biology of life by establishing circadian rhythms in organisms, tissues, and cells, thus regulating essential biological processes based on the day/night cycle. Circadian rhythms change over a lifetime due to maturation and aging, and disturbances in the control of the circadian system are associated with several age-related pathologies.

However, the impact of chronobiology and the circadian system on healthy organ and tissue aging remains largely unknown. Whether aging-related changes of the circadian system’s regulation follow a conserved pattern across different species and tissues, hence representing a common driving force of aging, is unclear.

Based on a cross-sectional transcriptome analysis covering 329 RNA-Seq libraries, we provide indications that the circadian system is subjected to aging-related gene alterations shared between evolutionarily distinct species, such as Homo sapiens, Mus musculus, Danio rerio, and Nothobranchius furzeri. We discovered differentially expressed genes by comparing tissue-specific transcriptional profiles of mature, aged, and old-age individuals and report on six genes (per2, dec2, cirp, klf10, nfil3, and dbp) of the circadian system, which show conserved aging-related expression patterns in four organs of the species examined. Our results illustrate how the circadian system and aging might influence each other in various tissues over a long lifespan and conceptually complement previous studies tracking short-term diurnal and nocturnal gene expression oscillations.

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DOI - https://doi.org/10.18632/aging.203788

Full Text - https://www.aging-us.com/article/203788/text

Correspondence to: Emanuel Barth email: emanuel.barth@uni-jena.de

Keywords: aging, circadian clock system, circadian rhythm, inter-species comparison, longevity, RNA-Seq

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 on:

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 please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls

Media Contact
18009220957
MEDIA@IMPACTJOURNALS.COM

The Circadian System and Aging

Aging-US published "DNA methylation-based measures of biological age: meta-analysis predicting time to death" in 2016, which reported that estimates of biological age based on DNA methylation patterns, often referred to as "epigenetic age", "DNAm age", have been shown to be robust biomarkers of age in humans.

These authors previously demonstrated that independent of chronological age, epigenetic age assessed in blood predicted all-cause mortality in four human cohorts. Here, they expanded their original observation to 13 different cohorts for a total sample size of 13,089 individuals, including three racial/ethnic groups. In addition, they examined whether incorporating information on blood cell composition into the epigenetic age metrics improves their predictive power for mortality.

All considered measures of epigenetic age acceleration were predictive of mortality, independent of chronological age, even after adjusting for additional risk factors.

The authors said, "DNA methylation-based biomarkers, often referred to as ‘epigenetic age’ or ‘epigenetic clock’, are robust estimators of chronological age of an individual."

This estimate is consistent across most types of biological specimens, including whole blood, brain, breast, kidney, liver, lung, and saliva and cell types, including CD4 T cells, monocytes, B cells, glial cells, and neurons.

It is well known that blood cell composition changes with age and some of these changes might be independent predictors of mortality. Thus, it is of interest to understand whether considering information on blood cell composition in measures of epigenetic age improves their predictive power for mortality.

Here, the authors evaluated the ability to predict time to death for blood-based epigenetic age measures, both published and novel measures that incorporate information on blood cell composition.

Due to the well documented age-related changes in blood cell composition, they were able to distinguish epigenetic measures of age that were independent of changes in blood cell composition, and measures that incorporated age-related changes in blood cell composition.

The Research Team concluded in their Aging-US Research Output, "our results inform the ongoing debate about whether epigenetic biomarkers of age capture an aspect of biological age. While epigenetic processes are unlikely to be the only mediators of chronological age on mortality—in fact, multiple risk factors have stronger effects on mortality—our results suggest that at least one of the mediating processes relates to the epigenetic age of blood tissue and that this process is independent of age-dependent changes in blood cell composition. Future studies will be useful for gaining a mechanistic understanding of this intrinsic epigenetic aging process."

Full Text - https://www.aging-us.com/article/101020/text/

Correspondence to: Steve Horvath email: shorvath@mednet.ucla.edu

Keywords: all-cause mortality, lifespan, epigenetics, epigenetic clock, DNA+methylation, mortality

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 on:

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 please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls

Media Contact
18009220957
MEDIA@IMPACTJOURNALS.COM

Author Insight: DNA Methylation-based Measures of Biological Age

Aging-US published "Epigenetic age of the pre-frontal cortex is associated with neuritic plaques, amyloid load, and Alzheimer’s disease related cognitive functioning" in 2015, which reported that there is an urgent need to develop molecular biomarkers of brain age in order to advance our understanding of age related neurodegeneration.

Here the authors use n=700 dorsolateral prefrontal cortex samples from Caucasian subjects of the Religious Order Study and the Rush Memory and Aging Project to examine the association between epigenetic age and Alzheimer’s disease related cognitive decline, and AD related neuropathological markers.

The neuropathological markers may mediate the association between epigenetic age and cognitive decline. Genetic complex trait analysis revealed that epigenetic age acceleration is heritable and has significant genetic correlations with diffuse plaques and possibly working memory. Overall, these results suggest that the epigenetic clock may lend itself as a molecular biomarker of brain age.

Dr. Steve Horvath said, "Cognitive aging is on a continuum from normality, to mild cognitive impairment (MCI), to dementia."

After the age of 65 the risk of developing a neurodegenerative form of dementia, such as Alzheimer’s Disease, has been shown to double every five years, and by age 85, the prevalence of dementia is estimated to be as high as 31%.

Epigenetic alterations, such as DNA methylation, have been linked to both AD pathology and cognitive aging in the absence of AD dementia.

Given that aging is associated with a normal loss in cognitive ability as well as the rapidly increasing susceptibility to AD, an aging biomarker based on DNAm could account for between-person differences in either the rate of cognitive aging among non-demented individuals or the rate of disease progression among those with AD.

As a result, the goals of their study were to:

1) Examine the association between DNAm age and AD neuropathology,
2) Test whether DNAm age relates to AD dementia status and measures of cognitive functioning,
3) Determine if differences in DNAm age reflect cognitive decline in persons with or with AD-dementia,
4) Examine whether neuropathology underlies the association between higher DNAm age and worse cognitive functioning.
They hypothesize that participants who have higher levels of neuropathology, lower cognitive functioning, and/or who are diagnosed with AD will have higher DNAm age in PFC samples at death—signifying that their brains are biologically older.

They also hypothesize that neuropathology will mediate the association between DNAm age and cognition.

The Horvath Research Team concluded in their Aging-US Research Output, "There are limitations to this study. First, DNAm age was only measured postmortem, which prevented us from determining if it was predictive of AD status or cognitive decline. Furthermore, DNAm age changes with time, yet in our sample it was only measured at a single time-point. For that reason we were unable to examine if larger changes in DLPFC DNAm age were associated with steeper cognitive decline or AD. Nevertheless, our study was strengthened by the inclusion of neuropathological variables, longitudinal measurements of multiple cognitive functioning domains, measurement of DNAm age in DLPFC rather than whole blood, and availability of postmortem data for neuropathologic indices. Overall, our study shows that epigenetic aging in DLPFC is associated with the severity of cognitive decline as well as neuropathological hallmarks of AD. These results strongly suggests that the epigenetic clock lend itself as a molecular biomarker of brain age."

Full Text - https://www.aging-us.com/article/1008...

Correspondence to: Steve Horvath email: shorvath@mednet.ucla.edu

Keywords: epigenetics, neuritic plaques, amyloids, cognitive functioning, memory, Alzheimer's disease, epigenetic clock, DNA methylation

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, 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 on:

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 please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls

Media Contact
18009220957
MEDIA@IMPACTJOURNALS.COM

Author Insight: Epigenetic Age of the Pre-frontal Cortex

CD Genomics

CD Genomics is committed to providing novel NGS services enabling researchers to explore structure and function of the microbial community in a high-resolution and culture-independent manner using technology from Illumina and PacBio. In addition, we also offer the service to sequence the genome of the individual cultured bacteria, fungi, phage or virus, whether do novo or re-sequencing.  https://www.cd-genomics.com/Microbial-Genomics.html

Microbial Genomics — CD Genomics

CD Genomics has been providing the accurate and affordable RNA-Seq (RNA sequencing) service for decades. We combine both Illumina (short reads) and PacBio (long reads) platforms to obtain the transcriptome that allows de novo assembly or re-sequencing for bacteria, plants, animals and humans. https://www.cd-genomics.com/RNA-Seq-Transcriptome.html

The Development and Workflow of RNA-seq — CD Genomics

CD genomics can provide microorganism quantification amplicon sequencing based on 16S external standard sequences to obtain absolute abundance data for species in the sample. The 16S amplicon library is constructed and sequenced by adding a synthetic sequence of known copy number to the sample DNA, and then a standard curve is drawn according to the number of amplicon reads and the absolute copy number of the external standard sequence. And finally the absolute copy number of the 16S rRNA gene of the corresponding species of the OTU representative sequence in the sample is calculated. More information at https://www.cd-genomics.com/absolute-quantitative-16s-18s-its-amplicon-sequencing.html

Genomics

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