4.7 Article

Scrutiny of genome-wide somatic mutation profiles in centenarians identifies the key genomic regions for human longevity

相关参考文献

注意:仅列出部分参考文献,下载原文获取全部文献信息。
Review Cardiac & Cardiovascular Systems

Somatic Mutations in Cardiovascular Disease

J. Brett Heimlich et al.

Summary: Advances in genomic sequencing have increased our understanding of the inherited basis of cardiovascular disease (CVD). Reanalysis of genomic datasets revealed somatically acquired DNA mutations as an unexpected risk factor for CVD. This review provides an overview of somatic mutations and their contributions to CVD, focusing on the most common manifestation of clonal hematopoiesis. The available data on how somatic mutations lead to tissue mosaicism in various forms of CVD are also reviewed, along with future research directions and technological advances.

CIRCULATION RESEARCH (2022)

Article Multidisciplinary Sciences

Somatic mutation rates scale with lifespan across mammals

Alex Cagan et al.

Summary: Through whole-genome sequencing of 208 intestinal crypts from 56 individuals, this study reveals that somatic mutation in mammals is dominated by endogenous mutational processes, and mutational signatures in different species show similarities to those in humans, though with variations in relative contribution. The study also finds a strong inverse relationship between somatic mutation rate and species lifespan, suggesting that somatic mutation rates are evolutionarily constrained and may contribute to aging.

NATURE (2022)

Article Multidisciplinary Sciences

ETS1 acts as a regulator of human healthy aging via decreasing ribosomal activity

Fu-Hui Xiao et al.

Summary: Through transcriptome analysis of long-lived individuals, it was found that the ribosome pathway is significantly down-regulated, likely controlled by the transcription factor ETS1, which can regulate the expression of ribosomal protein genes to reduce cellular senescence.

SCIENCE ADVANCES (2022)

Article Multidisciplinary Sciences

Discovering the drivers of clonal hematopoiesis

Oriol Pich et al.

Summary: Positive selection signals can be used to identify genes that drive clonal hematopoiesis in hematopoietic stem cells. By analyzing samples from two large cancer genomics cohorts, we obtained a list of nearly 70 candidate genes with positive selection signals. This approach can discover new CH genes and validate known CH genes.

NATURE COMMUNICATIONS (2022)

Article Oncology

Analysis of mutational signatures with yet another package for signature analysis

Daniel Huebschmann et al.

Summary: YAPSA is a tool for analyzing mutational signatures in tumor genomes, which can improve tumor classification and support therapeutic decisions. It includes features such as correcting triplet content and determining confidence intervals for signature exposures.

GENES CHROMOSOMES & CANCER (2021)

Article Pathology

Assessing Limit of Detection in Clinical Sequencing

Elizabeth R. Starks et al.

Summary: This study developed a theoretical model to predict the sensitivity of solid tumor sequencing, which was empirically validated through experiments. A workflow and formulas were provided to determine the limiting factors to sensitivity in different assay designs, offering useful guidance for clinical assay designers.

JOURNAL OF MOLECULAR DIAGNOSTICS (2021)

Review Cell Biology

From DNA damage to mutations: All roads lead to aging

Jan Vijg

Summary: Damage to genetic information in cells has been a challenge since the beginning of life, with DNA repair evolving as an early genetic trait to cope with this. Errors during DNA repair generate mutations, driving evolution through natural selection. DNA damage is considered the primary driver of degenerative processes leading to aging.

AGEING RESEARCH REVIEWS (2021)

Article Biochemistry & Molecular Biology

Increased stem cell proliferation in atherosclerosis accelerates clonal hematopoiesis

Alexander Heyde et al.

Summary: Clonal hematopoiesis, a condition where certain hematopoietic stem cell clones generate a disproportionate fraction of blood leukocytes, is correlated with increased risk for cardiovascular disease. Research shows that in individuals with atherosclerosis, hematopoietic stem cell division rates are elevated, leading to an increased risk of clonal hematopoiesis. The study suggests that increased hematopoietic stem cell proliferation is an important factor contributing to the association between cardiovascular disease and clonal hematopoiesis.
Article Multidisciplinary Sciences

Accurate SNV detection in single cells by transposon-based whole-genome amplification of complementary strands

Dong Xing et al.

Summary: A single-cell WGA method called META-CS has been developed to eliminate false positives in single-cell SNV detection, achieving the highest accuracy in measurements so far. Validation studies on kindred cells, human sperm, and other human tissues have confirmed the effectiveness of META-CS, revealing an increase in SNVs in mature single human neurons with age and cell type-dependent SNV frequencies and mutational patterns in single human blood cells.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

Article Multidisciplinary Sciences

Maintenance of genome sequence integrity in long-and short-lived rodent species

Lei Zhang et al.

Summary: Long-lived species demonstrate a higher capacity for accurate DNA damage repair, which may help slow down the aging process. The mutagen-induced mutation frequencies are inversely correlated with the maximum life span of different species, with the most significant difference observed between mice and other species.

SCIENCE ADVANCES (2021)

Article Multidisciplinary Sciences

Neuronal enhancers are hotspots for DNA single-strand break repair

Wei Wu et al.

Summary: Defects in DNA repair can lead to neurodevelopmental and neurodegenerative diseases, particularly in long-lived post-mitotic neurons. Neurons accumulate unexpectedly high levels of DNA single-strand breaks at specific sites within the genome, which are repaired by PARP1 and XRCC1-dependent mechanisms. Deficiencies in XRCC1-dependent repair in neurons can lead to increased DNA repair synthesis at neuronal enhancers, while defects in long-patch repair reduce synthesis, potentially contributing to neurodegenerative phenotypes in patients.

NATURE (2021)

Article Multidisciplinary Sciences

Somatic mutation landscapes at single-molecule resolution

Federico Abascal et al.

Summary: The study developed a method to detect mutations in single cells or small clones, revealing that somatic mutations also occur in non-dividing cells and contribute significantly to somatic mutagenesis.

NATURE (2021)

Article Multidisciplinary Sciences

Incorporation of a nucleoside analog maps genome repair sites in postmitotic human neurons

Dylan A. Reid et al.

Summary: Neurons, as the longest-lived cells in our bodies, lack DNA replication and rely on a limited repertoire of DNA repair mechanisms to maintain genome fidelity. Research has found that DNA repair in neurons is enriched at well-defined hotspots, which are associated with evolutionarily conserved elements of the human genome. These findings provide insights into the protection of genome integrity in the aging and disease of the nervous system.

SCIENCE (2021)

Article Biology

Whole-genome sequencing analysis of semi-supercentenarians

Paolo Garagnani et al.

Summary: People who reach extreme ages have a unique genetic background associated with efficient DNA repair mechanisms, which helps delay aging and protect from cardiovascular events. This genetic trait is characterized by lower mutation load compared to younger individuals, as shown in both germline and somatic mutation patterns.
Article Biochemistry & Molecular Biology

The DisGeNET cytoscape app: Exploring and visualizing disease genomics data

Janet Pinero et al.

Summary: The unbiased exploration of genomic variants has revealed hundreds of thousands of disease-associated loci, while network-based approaches are essential for understanding the molecular mechanisms underlying human diseases. The DisGeNET Cytoscape App integrates Cytoscape and DisGeNET functionalities to support various queries and analyses, offering a convenient tool for analyzing disease-related gene and variant networks.

COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL (2021)

Article Multidisciplinary Sciences

Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidatesfor targeted treatment

Hua Sun et al.

Summary: This study presents genomic landscapes of 536 patient-derived xenograft (PDX) models across 25 cancer types, providing insights into their molecular features and suitability for clinical trials. PDXs typically have higher purity than human tumors and are useful for investigating dynamic driver events and molecular properties, making them valuable tools in cancer research and drug development.

NATURE COMMUNICATIONS (2021)

Review Cell Biology

Centenarians: An excellent example of resilience for successful ageing

C. Borras et al.

MECHANISMS OF AGEING AND DEVELOPMENT (2020)

Article Multidisciplinary Sciences

The repertoire of mutational signatures in human cancer

Ludmil B. Alexandrov et al.

NATURE (2020)

Article Multidisciplinary Sciences

A case report of multiple primary prostate tumors with differential drug sensitivity

Scott Wilkinson et al.

NATURE COMMUNICATIONS (2020)

Article Multidisciplinary Sciences

The mutational constraint spectrum quantified from variation in 141,456 humans

Konrad J. Karczewski et al.

NATURE (2020)

Review Biochemistry & Molecular Biology

Pathogenic Mechanisms of Somatic Mutation and Genome Mosaicism in Aging

Jan Vijg et al.

Article Multidisciplinary Sciences

Inherited causes of clonal haematopoiesis in 97,691 whole genomes

Alexander G. Bick et al.

NATURE (2020)

Article Multidisciplinary Sciences

Single-cell whole-genome sequencing reveals the functional landscape of somatic mutations in B lymphocytes across the human lifespan

Lei Zhang et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

Article Multidisciplinary Sciences

A meta-analysis of genome-wide association studies identifies multiple longevity genes

Joris Deelen et al.

NATURE COMMUNICATIONS (2019)

Article Biochemistry & Molecular Biology

CADD: predicting the deleteriousness of variants throughout the human genome

Philipp Rentzsch et al.

NUCLEIC ACIDS RESEARCH (2019)

Article Biochemistry & Molecular Biology

Transcriptome evidence reveals enhanced autophagy-lysosomal function in centenarians

Fu-Hui Xiao et al.

GENOME RESEARCH (2018)

Article Multidisciplinary Sciences

Protein carbamylation is a hallmark of aging

Laetitia Gorissea et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2016)

Article Genetics & Heredity

Clock-like mutational processes in human somatic cells

Ludmil B. Alexandrov et al.

NATURE GENETICS (2015)

Article Biochemical Research Methods

PyClone: statistical inference of clonal population structure in cancer

Andrew Roth et al.

NATURE METHODS (2014)

Article Public, Environmental & Occupational Health

The Epidemiology of Longevity and Exceptional Survival

Anne B. Newman et al.

EPIDEMIOLOGIC REVIEWS (2013)

Article Multidisciplinary Sciences

Evidence of non-random mutation rates suggests an evolutionary risk management strategy

Inigo Martincorena et al.

NATURE (2012)

Article Biochemistry & Molecular Biology

Protein carbamylation links inflammation, smoking, uremia and atherogenesis

Zeneng Wang et al.

NATURE MEDICINE (2007)

Article Biochemical Research Methods

Pathway level analysis of gene expression using singular value decomposition

J Tomfohr et al.

BMC BIOINFORMATICS (2005)

Article Multidisciplinary Sciences

Distinct spectra of somatic mutations accumulated with age in mouse heart and small intestine

MET Dollé et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2000)