The biological age of human tissues and cells may be younger or older than the expected chronological age.  Many genetic and environmental factors can contribute to this difference.  Recently, scientists have developed various clocks to measure the biological age in humans.  Among them, the Horvath epigenetic aging clock, a multi-tissue predictor of age, is the most widely used one.  It can cover both pre- and postnatal lifespans and has proven to be accurate.  However, it remains unknown how its clock ticking rate is controlled.It was believed that the epigenetic aging clocks tick due to the erosion of a hypothetical “epigenetic maintenance system”, in which the epigentic genes set the ticking rate.Epigenetic genes encode proteins that modify DNA or histone proteins chemically, which can in turn change the binding or access of regulatory proteins (i. e. transcription factors) to the DNA regions that control gene expression (i. e. promoters and enhancers), thus affecting gene expression.  Unlike genetic mutations, epigenetic modifications are reversible, do not change DNA or protein sequences, and can occur in response to environmental and developmental cues.The Horvath clock is made of mathematical models, which are based on a small set of cytosine methylation (mC) changes at the CpG (“p” represents a phosphodiester bond between cytosine and guanine) sites in the human genome. About one half of the CpG sites increases in methylation while the other half decreases during aging. The clock is set near “zero” for newborn cells, such as embryonic and pluripotent stem cells, and the “time” increases due to the methylation changes.  For each tissue, the clock has a unique aging rate. The DNA methylation data can be obtained applying blood samples to the Illumina Human-Methylation450 array (450K array), and the “time” value can be calculated using an online calculator of computational algorithms (https://dnamage.genetics.ucla.edu/home).A study by \citet{Martin_Herranz_2019} has identified NSD1, the first gene in the “epigenetic maintenance system” to have accelerated the Horvath aging clock.  The team screened for the epigenetic genes that could accelerate the ticking rate of the Horvath clock in the patients who suffered from developmental diseases due to the mutations of these genes. They measured the clock aging rate in blood samples and found that only the Sotos syndrome patients had significantly accelerated clock aging rate.  Sotos syndrome is caused by NSD1 mutations and has a range of aging-like developmental symptoms such as “prenatal and postnatal overgrowth, facial gestalt, advanced bone age, developmental delay, higher cancer predisposition, and, in some cases, heart defects”.NSD1 encodes a Histone H3 lysine 36 (H3k36) methyltransferase, an epigenetic regulatory enzyme that can add a mono- or di-methyl group to the 36th amino acid, lysine (K), of the histone H3 protein.  Histone H3 is one of eight histone proteins packing the genomic DNA to form nucleosomes.The researchers then conducted genome-wide analyses, confirming that the NSD1 mutations in Sotos syndrome affected many CpG methylation sites, some of which were also affected by aging. The measurement strategy was more accurate than the Horvath clock because the calibrations used a large number of control samples and a microarray-based method.Previous studies support that NSD1 can change the ticking rate. For example, NSD1 can affect DNA methylation indirectly by interacting with DNA methylation machinery.  Several NSD1 interacting proteins in humans or their homologs in other species have been shown to affect the aging rate.This study has established the pivotal role of the H3k36 methyltransferase gene, NSD1, in the epigenetic maintenance system to determine the ticking rate of the epigenetic aging clock.  It showed that the clock is at least partially controlled genetically, if not entirely. Interestingly, the clock may have a functional role in the aging process.  This study has provided an excellent model for investigating many questions related to the human aging rate.The aging clock, due to its reversible epigenetic nature, may be reset with proper intervention, including keeping a healthy life style such as eating a low-calorie diet, exercising , and staying happy and positive.Author ORCiDAlison Liu https://orcid.org/0000-0003-0171-6441

Myles Axton

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Research in genetics provides the basis for understanding the function and evolution of all living things. The disciplines of reading and writing genomes translate into sustainable economic development with the rational global goals of food security, maternal and child health, precision medicine, education and access to informatics technologies. We believe that many publications in our field are motivated by these goals and contain reusable modular elements that can be recombined both in research and in its translation, to attain them. Open research entails sharing not only the conclusions of science, but its materials, provenance and gestation for the widest reuse by human and computational users. This means that we and our readers deplore any hiding or obscuring datasets or methods, and regret datasets in formally public repositories that have very slow accession or transfer rates. However, we will endeavor to work with all data producers who make contributions in good faith to genetics and genomics research.Genetics & Genomics Next (GGN ) is an Open Research journal from Wiley, published online using the CC-BY 4.0 open attribution license to encourage maximum credit and rapid creative reuse of all scholarly work. We are delighted to receive original research Articles, Resources, Analysis, Technical Reports and Perspectives in the areas of human, animal, plant and microbial genetics, genomics and epigenomics, selecting those reports for peer review that we judge editorially to have the highest research utility, ethical standards and societal impact. As professional, full-time editors at Wiley, we take responsibility for all manuscript decisions and peer reviewer assignment. Our Advisory Board Members have a complementary role to guide GGN’s mission as they see fit, anticipating the evolution of research and standards in our field, and, with us, providing leadership in promoting excellence in open research. Unlike Editorial Board members at some journals, GGN advisors are our mentors, not manuscript editors. We welcome their commitment to the journal for as long as they wish, and advisors may leave or rejoin the board at will.Since we offer an online journal, we are happy to consider reports in any format for peer review, provided they would not burden referees with their unusual length or complexity. We also welcome pre-submission enquiries via our online database (https://mc.manuscriptcentral.com/ggn). Author and dataset contributions and consortium roles can be described via the CRediT contributor taxonomy (https://www.casrai.org/credit.html). We support a range of community standards and databases and the FAIRSharing \cite{Sansone_2019} community standards site (https://fairsharing.org) for best practices and semantic precision. The journal endorses the FAIR \cite{Wilkinson_2016} data principles  (https://www.go-fair.org/fair-principles/) and we recommend database submission of datasets and workflows to replace most of the prior use cases for Supplementary Information.Research Articles should offer a new and substantial conceptual advance based on original experimental research and data, whereas Technical Reports need only detail a useful new method. Perspectives are literature reviews that set standards or propose future strategies in our field. Analysis articles offer opportunity to generate and test new hypotheses by interoperating or reusing existing datasets with new workflows. Resources provide provenance and curation of new datasets that will be of use to the community. If submissions are outside the scope of the journal or if editors consider them premature with respect to their field, we will make customized recommendation for appropriate Wiley journals that would peer review the work or suggest revisions that would typically qualify the work for peer review.Enabling the market for genomics-based ideas needs generosity with rich metadata and careful attention to semantic precision, as well as a sensitive understanding of the legal, ethical and economic underpinning of resources based in the code and the families of living people. For an editor, this means having patience in the face of the many exceptions to the ideal of publicly funded, universal research access to all human, animal and plant genomes and their associated traits and measurements. The resource-benefit balance is ever-present, and legal and ethics frameworks of genetic research evolve slowly in the legacy of past abuses of concepts of heredity. It is therefore essential that we recognize those data license conditions that aim to preserve participation of research subjects, build local resources and capacity and return benefits to the societies that initiated the studies. So, when genetics advances only on the terms of a commercial animal breeder or a security-conscious government, the conclusions and resources offered in the publication need to be maximized for reuse without derailing the sustainable long-term commitment of those producers to make their results available. Even in the sphere of publicly funded data resources in developed countries, it may be networks of excellence (consortia) spanning continents, institutions and generations of diverse funding sources that are the guarantors of the security of the research subjects’ data and the translational success of the research. Publishers looking for a highly cited paper - or data reusers looking to test their new algorithm - need to see where they fit in, and lobby for greater FAIRness from well-funded data generators. Proof of the reuse and interoperability of open research rests with the data users, so data providers need to enable and encourage their work.Author ORCiDsMyles Axton https://orcid.org/0000-0002-8042-4131Alison Liu https://orcid.org/0000-0003-0171-6441
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Preparing the submissionPerspective is a type of Review offering new insights, standards and strategic directions for the field, derived from selective reanalysis of the existing literature. There is no word limit, but to ensure timely review, we recommend 2 display items, 2 text boxes, 3,000 words main text and unlimited references.Submissions should be made via the online manuscript tracking system.  For technical help with the submission system, please contact ggn@wiley.com. Initial submission does not need to be formatted to Genetics & Genomics Next style.  For ease of evaluation and submission, the journal recommends an editable Word .docx or Authorea text document and a single merged PDF that includes all parts of main text and high-resolution figures embedded into the file.  A suitable PDF will be constructed by uploading text and figures using the online manuscript tracking system.  Genetics & Genomics Next does not impose word count and figure limits.  Table 1 contains the journal’s suggestions so that the manuscript is respectful of reader time and are readable by specialist and generalist alike.AcknowledgementsAuthors should list all funding sources here, please check Open Funder Registry. Contributions and material support from anyone not listed as an author should be acknowledged here, with permission from the contributor. Thanks to anonymous reviewers are not allowed.Conflict of Interest StatementAll authors are required to declare if they have potential conflicts of interest related to the submission, or none. This declaration shall be published. Submitting authors shall confirm all co-authors agree with the final statement.AbstractWhat is known in the field, for a general readership. Define the area and knowledge for a specialist.Explain the motivation and need for the research defined by the gap in existing knowledge.State your main claim or finding . Support that with evidence, statistics and detail, mentioning essential methods and analytical techniques that provided the evidence.State the meaning and significance of your new results for research in the field.End by suggesting realistic immediate implications and uses of your findings in your field and more broadly.Use as many subheading as you have main claims and topicsGive credit to and cite all the primary research publications that lay the background to this work including those to be discussed in the Discussion. Give context as to whether these are essential methods and analytic strategies or experimental findings. Ensure that claims of  causation, correlation and conjecture are distinguished. Make the main claims in logical order, supported by display items Discussion Summarize and evaluate the robustness and meaning of the main findings in light of existing publications. Be skeptical and discuss any limitations of the study and conditions where the results may or may not be applicable. Make a strong conclusion.References [terms in brackets will be removed before publication]1. [article] Wood WG, Eckert GP, Igbavboa U, Muller WE. Statins and neuroprotection: a prescription to move the field forward. Ann N Y Acad Sci 2010; 1199:69-76. 2. [book] Hoppert, M. Microscopic techniques in biotechnology. Weinheim: Wiley-VCH; 2003.3. [dataset]Authors; Year; Dataset title; Data repository or archive; Version (if any); Persistent identifier (e.g. DOI)4. [URI, GWAS summary statistics] Savage, J.E. et al. Genome-wide association meta-analysis in 269,867      individuals identifies new genetic and functional links to intelligence      https://www.ebi.ac.uk/gwas/studies/GCST006250 (2018)5. [supplementary data] Jagadeesan, A. et al. MDS/PCA plots within West Africa    https://doi.org/10.6084/m9.figshare.5640931 (2017)Tables or Boxes (each table or box complete with title and footnotes)      
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Preparing the submissionSubmissions should be made via the online manuscript tracking system.  For technical help with the submission system, please contact ggn@wiley.com. Initial submission does not need to be formatted to Genetics & Genomics Next style.  For ease of evaluation and submission, the journal recommends an editable Word .docx or Authorea text document and a single merged PDF that includes all parts of main text and high-resolution figures embedded into the file.  A suitable PDF will be constructed by uploading text and figures using the online manuscript tracking system.  Genetics & Genomics Next does not impose word count and figure limits.  Table 1 contains the journal’s suggestions so that the manuscript is respectful of reader time and are readable by specialist and generalist alike.AcknowledgementsAuthors should list all funding sources here, please check Open Funder Registry. Contributions and material support from anyone not listed as an author should be acknowledged here, with permission from the contributor. Thanks to anonymous reviewers are not allowed.Conflict of Interest StatementAll authors are required to declare if they have potential conflicts of interest related to the submission, or none. This declaration shall be published. Submitting authors shall confirm all co-authors agree with the final statement.AbstractWhat is known in the field, for a general readership. Define the area and knowledge for a specialist.Explain the motivation and need for the research defined by the gap in existing knowledge.State your main claim or finding . Support that with evidence, statistics and detail, mentioning essential methods and analytical techniques that provided the evidence.State the meaning and signficance of your new results for research in the field.End by suggesting realistic immediate implications and uses of your findings in your field and more broadly.IntroductionGive credit to and cite all the primary research publications that lay the background to this work including those to be discussed in the Discussion. Give context as to whether these are essential methods and analytic strategies or experimental findings. Ensure that causation, correlation and conjectureResults Make the main claims in logical order, supported by display items and methodsDiscussion Summarize and evaluate the robustness and meaning of the main findings in light of existing publications. Be skeptical and discuss any limitations of the study and conditions where the results may or may not be applicableMaterials and MethodsMethods and materials transparencyOffer methods used in the analysis, and materials used to conduct the research to any researcher for purposes of reproducing the results or replicating the procedure.  Indicate any restrictions on analytic methods including software, and tools and study materials available to other researchers. Specify how, where and when that material will be available.  If an existing method or tool is used in the research, the authors are responsible for checking the license and state confirmation of permission.To obtain Research Resource Identifiers (RRIDs): Use the Resource Identification Portal .Design and analysis transparencyAuthors are encouraged to review standards for disclosing key aspects of the research design and data analysis at http://www.equator-network.org/ and use those that are relevant for their research. Research reporting standards are widely adopted in our field, and exceeding their evolving requirements is essential to sustain the impact of genetics and genomics for research and for society.  Here is the current list of reporting standards, vocabularies, models, schemas and databases that we recommend we recommend at FAIRsharing.org.Human studies and research participantsIdentify the ethics committee that approved the human study, and that the study conforms to recognized standards, for example: Declaration of Helsinki; US Federal Policy for the Protection of Human Subjects; or European Medicines Agency Guidelines for Good Clinical Practice. If no formal ethics committee is available, state that the research was carried out in accordance with recognized standards (e.g. the Declaration of Helsinki, as revised in 2013).Images and information from individual participants, including participants from patient registries and databases, will only be published where the authors have obtained the individual's free prior informed consent. Authors do not need to provide a copy of consent forms to the publisher but, in signing the author license to publish, authors are required to confirm that specific informed consent to publish the image has been obtained. Wiley has a standard patient consent form available for authors to use if required. This requirement to obtained informed consent applies whether or not patients are identifiable from the information presented in the submission.Animal studiesFor submissions involving animal studies, state the protocol and procedures employed were ethically reviewed and approved, and the name of the organization giving approval. State whether experiments were performed in accordance with relevant institutional and national guidelines and regulations for the care and use of laboratory animals:US authors should cite compliance with the US National Research Council's Guide for the Care and Use of Laboratory Animals, the US Public Health Service's Policy on Humane Care and Use of Laboratory Animals, and Guide for the Care and Use of Laboratory Animals.UK authors should conform to UK legislation under the Animals (Scientific Procedures) Act 1986 Amendment Regulations (SI 2012/3039).EU authors should conform to Directive 2010/63/EU.Cell line authentication Declare where the cells were obtained, whether the cell lines have been tested and authenticated and the method by which the cells were tested. If cells were obtained directly from a cell bank that performs cell line characterizations and passaged in the user’s laboratory for fewer than 6 months after receipt or resuscitation, re-authentication is not required. Data Availability StatementPlease choose text from Table 3 and provide a citation to available data in the References list. These sequence data have been submitted to the DDBJ/EMBL/GenBank databases under accession number XXXXX  Gene expression data (derived from microarrays or sequencing) has been deposited to a MIAME- or MINSEQE-compliant public repository like the Gene Expression Omnibus (GEO) with accession XXXXXProtein Sequence Data should be submitted to UniProt with accession XXXXXReferences [terms in brackets will be removed before publication]1. [article] Wood WG, Eckert GP, Igbavboa U, Muller WE. Statins and neuroprotection: a prescription to move the field forward. Ann N Y Acad Sci 2010; 1199:69-76. 2. [book] Hoppert, M. Microscopic techniques in biotechnology. Weinheim: Wiley-VCH; 2003.3. [dataset]Authors; Year; Dataset title; Data repository or archive; Version (if any); Persistent identifier (e.g. DOI)4. [URI, GWAS summary statistics] Savage, J.E. et al. Genome-wide association meta-analysis in 269,867      individuals identifies new genetic and functional links to intelligence      https://www.ebi.ac.uk/gwas/studies/GCST006250 (2018)5. [supplementary data] Jagadeesan, A. et al. MDS/PCA plots within West Africa    https://doi.org/10.6084/m9.figshare.5640931 (2017)Tables (each table complete with title and footnotes)      
Chronic inflammation has been associated with numerous diseases, and many old people suffer from chronic inflammatory illnesses; however, the connections between age and inflammation are still obscure.Aging is marked by an overall decline of tissue and cellular functions. At the cellular level, it is accompanied with damages to DNA, RNA, and impairments of protein functions. Organisms can detect these damages and elicit innate immune responses to remove aged, dying or dead cells, and cell debris from tissues. However, as the cells of innate immunity age, their reduced energy production may hinder the clearance processes, which require energy, thus, the persistence of this debris in tissues, resulting in subsequent inflammatory responses. Cytokines accumulated during inflammation could further deteriorate local tissues and accelerate the aging process.Benayoun et al. \cite{Benayoun_2019} used machine learning that is capable of data-training, self-improvement, and prediction to investigate epigenomic (three histone marks) and transcriptomic landscapes in mice during the aging process and generated by far the largest datasets, using multiple tissues such as heart, liver, cerebellum, olfactory bulb, and primary culture of neural stem cells from young, middle-aged, and old mice. The researchers determined epigenomic states that could predict transcriptional changes at specific genomic loci during aging. They found that, in all examined tissues, the interferon response pathway was robustly activated, perhaps to detect DNA damages and the expression of retrovirus-like transposons, and that multiple innate immune pathways were also upregulated significantly. These results strongly supported the conclusion that inflammation is a commonly shared hallmark for vertebrate aging tissues.If we can reduce or prevent the inflammation process, aged tissues may be rejuvenated and prolonged for their normal functions. These transcription factors provide potential targets for pharmaceutical development and therapeutic strategies for healthy aging.Author ORCiDAlison Liu https://orcid.org/0000-0003-0171-6441
A new method  \cite{Ludwig_2019} traces the cellular relationship and hierarchies (the “pedigrees”) of human cells within the body by reading the DNA sequences of hundreds to thousands of mitochondria extracted from single cells.Various genetic labeling techniques have been developed for lineage tracing in other model organisms. However, the above techniques are not applicable in intact humans. Cell lineage tracing is the most direct way to understand the development of complex cell types and their relationships in an organism, and an important method to trace abnormal cells over time to monitor developmental mosaicism, as demonstrated in C. elegans . In mammals, cell lineage tracing is particularly important for tracing cancer cells and their migration because cancers present special difficulties due to fast-paced proliferation and sequential genetic mutations. Lineage tracing can also determine if transplantation is successful and transplanted cells or tissues are on the correct site.The researchers showed that single-cell RNA sequencing (RNA-seq) and transposase accessible chromatin sequencing (ATAC-seq) methods could be used in combination to trace the inheritance of mitochondrial mutations, chromosomal states, and gene expressions at the same time, in multiple human cell colonies obtained from cultured cells, multiple human tissues, tumor cells, and transplanted cells.  ATAC-seq detects the regions of chromosomes that are not wrapped into nucleosomes by histone proteins, thus defining cellular or chromosomal states.  Using this method, they identified large numbers of mitochondrial DNA mutations and heteroplasmy (the presence of different types of mitochondrial genomes) that were associated with specific cell populations, tissues, or individuals. These experiments led to an important conclusion that mitochondrial mutations were inherited in the cellular colonies with extensive divisions stably and without being affected by cellular or chromosomal state, and the high mutation rate in mitochondrial DNA allows cellular sub-colonies to be traced with high resolution.Thus, the single-cell sequencing of mitochondrial DNA mutations provides a method that is much more accurate, stable, and affordable than a single-cell genome sequencing method to study clonal architecture in human health and diseases.Author ORCiDAlison Liu https://orcid.org/0000-0003-0171-6441