Aging and neurodegeneration are associated with increased mutations in single human neurons
Open accessPublished version of a preprint
Abstract
Brain mutations, young and old: Most neurons that make up the human brain are postmitotic, living and functioning for a very long time without renewal (see the Perspective by Lee). Bae et al. examined the genomes of single neurons from the prenatal developing human brain. Both the type of mutation and the rates of accumulation changed between gastrulation and neurogenesis. These early mutations could be generating useful neuronal diversity or could predispose individuals to later dysfunction. Lodato et al. also found that neurons take on somatic mutations as they age by sequencing single neurons from subjects aged 4 months to 82 years. Somatic mutations accumulated with increasing age and accumulated faster in individuals affected by inborn errors in DNA repair. Postmitotic mutations might only affect one neuron, but the accumulated divergence of genomes across the brain could affect function. Science , this issue p. 550 , p. 555 ; see also p. 521
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Somatic variants accumulate in all cell types that have been studied, both during normal development and during aging.
“Somatic variants accumulate in all cell types that have been studied, both during normal development and during aging16–18.”
From Somatic cancer variants enriched in Alzheimer’s disease microglia-like cells drive inflammatory and proliferative states (2026) · cites this paper as [16]
The Main Text reports that somatic single-nucleotide variants accumulate with age in human neurons and notes that variants are already present in fetal progenitor cells. It does not establish accumulation during both development and aging in all studied cell types; its direct analysis is limited to neurons. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPrevious studies suggested DNA damage increases with age in human brain.
“Previous studies have suggested that DNA damage increases with age in the human brain.62,63”
From Uncovering the signatures of aging and senescence in the human dorsolateral prefrontal cortex (2026) · cites this paper as [62]
DNA mutations can now be accurately determined and have been shown to accumulate with age in humans and mice in a tissue-specific manner.
“However, DNA mutations, a consequence of erroneous DNA repair, can now be accurately determined and have been shown to accumulate with age in humans and mice in a tissue-specific manner42,107–110.”
From The central role of DNA damage in the ageing process (2021) · cites this paper as [42]
Previous studies have shown increased neuronal genomic mosaicism (including SNVs, copy number variations, and cDNA insertions) in neurodegeneration.
“Previous studies have shown increased neuronal genomic mosaicism (including SNVs, copy number variations, and cDNA insertions in neurodegeneration)124–128.”
From Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration (2023) · cites this paper as [124]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482 · see citing works
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607 · see citing works
Gene Ontology: tool for the unification of biology
Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., et al. (2000) · Nature Genetics · doi:10.1038/75556 · Cited by 43,206 · see citing works
The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data
McKenna, A., Hanna, M., Banks, E., Sivachenko, A., Cibulskis, K., Kernytsky, A., Garimella, K., Altshuler, D., Gabriel, S., Daly, M., et al. (2010) · Genome Research · doi:10.1101/gr.107524.110 · Cited by 27,895 · see citing works
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982 · see citing works
dbSNP: the NCBI database of genetic variation
Sherry, S. T. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.1.308 · Cited by 7,502 · see citing works
Bootstrap Methods and their Application
Davison, A. C., & Hinkley, D. V. (1997) · doi:10.1017/cbo9780511802843 · Cited by 7,350 · see citing works
Gene ontology analysis for RNA-seq: accounting for selection bias
Young, M. D., Wakefield, M. J., Smyth, G. K., & Oshlack, A. (2010) · Genome Biology · doi:10.1186/gb-2010-11-2-r14 · Cited by 7,107 · see citing works
Neurogenesis in the adult human hippocampus
Eriksson, P. S., Perfilieva, E., Björk-Eriksson, T., Alborn, A.-M., Nordborg, C., Peterson, D. A., & Gage, F. H. (1998) · Nature Medicine · doi:10.1038/3305 · Cited by 6,369 · see citing works
Mapping identifiers for the integration of genomic datasets with the R/Bioconductor package biomaRt
Durinck, S., Spellman, P. T., Birney, E., & Huber, W. K. (2009) · Nature Protocols · doi:10.1038/nprot.2009.97 · Cited by 4,081 · see citing works
Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence
Genovese, G., Kähler, A. K., Handsaker, R. E., Lindberg, J., Rose, S. A., Bakhoum, S. F., Chambert, K., Mick, E., Neale, B. M., Fromer, M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1409405 · Cited by 3,531 · see citing works
Gene regulation and DNA damage in the ageing human brain
Lu, T., Pan, Y., Kao, S.-Y., Li, C., Kohane, I., Chan, J., & Yankner, B. A. (2004) · Nature · doi:10.1038/nature02661 · Cited by 1,874 · see citing works
The human brain in numbers: a linearly scaled-up primate brain
Herculano-Houzel, S. (2009) · Frontiers in Human Neuroscience · doi:10.3389/neuro.09.031.2009 · Cited by 1,778 · see citing works
High burden and pervasive positive selection of somatic mutations in normal human skin
Martincorena, I., Roshan, A., Gerstung, M., Ellis, P., Van Loo, P., McLaren, S., Wedge, D. C., Fullam, A., Alexandrov, L. B., Tubio, J. M., et al. (2015) · Science · doi:10.1126/science.aaa6806 · Cited by 1,770 · see citing works
Deciphering Signatures of Mutational Processes Operative in Human Cancer
Alexandrov, L. B., Nik‐Zainal, S., Wedge, D. C., Campbell, P. J., & Stratton, M. R. (2013) · Cell Reports · doi:10.1016/j.celrep.2012.12.008 · Cited by 1,277 · see citing works
Understanding nucleotide excision repair and its roles in cancer and ageing
Marteijn, J. A., Lans, H., Vermeulen, W., & Hoeijmakers, J. H. J. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3822 · Cited by 1,192 · see citing works
Dean, F. B., Nelson, J. R., Giesler, T. L., & Lasken, R. S. (2001) · Genome Research · doi:10.1101/gr.180501 · Cited by 1,070 · see citing works
Endogenous DNA damage in humans: a review of quantitative data
Bont, R. D. (2004) · Mutagenesis · doi:10.1093/mutage/geh025 · Cited by 1,065 · see citing works
Clock-like mutational processes in human somatic cells
Alexandrov, L. B., Jones, P. H., Wedge, D. C., Sale, J. E., Campbell, P. J., Nik‐Zainal, S., & Stratton, M. R. (2015) · Nature Genetics · doi:10.1038/ng.3441 · Cited by 1,038 · see citing works
Rate, molecular spectrum, and consequences of human mutation
Lynch, M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912629107 · Cited by 792 · see citing works
On the nature of the aging process
Szilard, L. (1959) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.45.1.30 · Cited by 651 · see citing works
Somatic mutation in single human neurons tracks developmental and transcriptional history
Lodato, M. A., Woodworth, M. B., Lee, S., Evrony, G. D., Mehta, B. K., Karger, A., Lee, S., Chittenden, T. W., D’Gama, A. M., Cai, X., et al. (2015) · Science · doi:10.1126/science.aab1785 · Cited by 570 · see citing works
Self-citationMultiple evidence strands suggest that there may be as few as 19 000 human protein-coding genes
Ezkurdia, I., Juan, D., Rodrı́guez, J. M., Frankish, A., Diekhans, M., Harrow, J., Vázquez, J., Valencia, A., & Tress, M. L. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu309 · Cited by 551 · see citing works
Single-Neuron Sequencing Analysis of L1 Retrotransposition and Somatic Mutation in the Human Brain
Evrony, G. D., Cai, X., Lee, E., Hills, L. B., Elhosary, P. C., Lehmann, H. S., Parker, J. J., Atabay, K. D., Gilmore, E. C., Poduri, A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.09.035 · Cited by 548 · see citing works
Self-citationSingle-Cell Exome Sequencing and Monoclonal Evolution of a JAK2-Negative Myeloproliferative Neoplasm
Hou, Y., Song, L., Zhu, P., Zhang, B., Tao, Y., Xu, X., Li, F., Wu, K., Liang, J., Shao, D., et al. (2012) · Cell · doi:10.1016/j.cell.2012.02.028 · Cited by 541 · see citing works
Genome-wide Single-Cell Analysis of Recombination Activity and De Novo Mutation Rates in Human Sperm
Wang, J., Fan, H. C., Behr, B. R., & Quake, S. R. (2012) · Cell · doi:10.1016/j.cell.2012.06.030 · Cited by 511 · see citing works
A Quantitative Comparison of Single-Cell Whole Genome Amplification Methods
de Bourcy, C. F. A., Vlaminck, I. D., Kanbar, J. N., Wang, J., Gawad, C., & Quake, S. R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0105585 · Cited by 305 · see citing works
Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder
Lim, E. T., Uddin, M., De Rubeis, S., Chan, Y., Kamumbu, A. S., Zhang, X., D'Gama, A. M., Kim, S. N., Hill, R. S., Goldberg, A. P., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4598 · Cited by 299 · see citing works
Self-citationTranscription-associated mutational asymmetry in mammalian evolution
Program, N. C. S., Green, P., Ewing, B., Miller, W., Thomas, P. J., & Green, E. D. (2003) · Nature Genetics · doi:10.1038/ng1103 · Cited by 285 · see citing works
Cell lineage analysis in human brain using endogenous retroelements
Evrony, G. D., Lee, E., Mehta, B. K., Benjamini, Y., Johnson, R. M., Cai, X., Yang, L., Haseley, P., Lehmann, H. S., Park, P. J., et al. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.028 · Cited by 269 · see citing works
Self-citationHoang, M. L., Kinde, I., Tomasetti, C., McMahon, K. W., Rosenquist, T. A., Grollman, A. P., Kinzler, K. W., Vogelstein, B., & Papadopoulos, N. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1607794113 · Cited by 224 · see citing works
THE AGING PROCESS AND CANCEROGENESIS
Failla, G. (1958) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1958.tb46828.x · Cited by 215 · see citing works
Decontamination of MDA Reagents for Single Cell Whole Genome Amplification
Woyke, T., Sczyrba, A., Lee, J., Rinke, C., Tighe, D., Clingenpeel, S. R., Malmstrom, R. R., Stepanauskas, R., & Cheng, J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026161 · Cited by 206 · see citing works
Dollé, M. E. T., Busuttil, R. A., Garcia, A. M., Wijnhoven, S., van Drunen, E., Niedernhofer, L. J., van der Horst, G. T. J., Hoeijmakers, J. H. J., STEEG, H. V., & Vijg, J. (2006) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2005.11.008 · Cited by 109 · see citing works
Transcription induces strand-specific mutations at the 5′ end of human genesPreprint
Polak, P. P., & Arndt, P. F. (2008) · Genome Research · doi:10.1101/gr.076570.108 · Cited by 107 · see citing works
Hazen, J. L., Faust, G. G., Rodriguez, A. R., Ferguson, W. C., Shumilina, S., Clark, R. A., Boland, M. J., Martin, G., Chubukov, P., Tsunemoto, R. K., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.02.004 · Cited by 92 · see citing works
Mutational fingerprints of aging
Dolle, M. E. T. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.2.545 · Cited by 87 · see citing works
A polymerase chain reaction-based method to detect cisplatin adducts in specific genes
Jennerwein, M. M., & Eastman, A. R. (1991) · Nucleic Acids Research · doi:10.1093/nar/19.22.6209 · Cited by 84 · see citing works
Lesions in DNA: hurdles for polymerases
Baynton, K., & Fuchs, R. P. (2000) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(99)01524-8 · Cited by 77 · see citing works
Premature aging and cancer in nucleotide excision repair-disorders
Diderich, K. E. M., Alanazi, M. A., & Hoeijmakers, J. H. J. (2011) · DNA repair · doi:10.1016/j.dnarep.2011.04.025 · Cited by 71 · see citing works
Prefrontal cortex cytoarchitecture in normal aging and Alzheimer’s disease: a relationship with IQ
van Veluw, S. J., Sawyer, E. K., Clover, L. M., Cousijn, H., de Jager, C., Esiri, M. M., & Chance, S. A. (2012) · Brain Structure and Function · doi:10.1007/s00429-012-0381-x · Cited by 59 · see citing works
Intra-Organ Variation in Age-Related Mutation Accumulation in the Mouse
Busuttil, R. A., Garcı́a, A. M., Reddick, R. L., Dollé, M. E. T., Calder, R. B., Nelson, J. F., & Vijg, J. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000876 · Cited by 59 · see citing works
Crabtree, G. R. (2012) · Trends in Genetics · doi:10.1016/j.tig.2012.10.002 · Cited by 56 · see citing works
Structural Genetic Variation in the Context of Somatic Mosaicism
Dumanski, J. P., & Piotrowski, A. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-507-7_12 · Cited by 35 · see citing works
Giese, H., Dollé, M. E. T., Hezel, A. F., STEEG, H. V., & Vijg, J. (1999) · Oncogene · doi:10.1038/sj.onc.1202404 · Cited by 34 · see citing works
Sherman, M. A., Barton, A. R., Lodato, M. A., Vitzthum, C. M., Coulter, M. E., Walsh, C. A., & Park, P. J. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1195 · Cited by 16 · see citing works
Self-citationA method for detecting genetic toxicity using the RNA synthesis response to DNA damage
Morita, Y., Iwai, S., & Kuraoka, I. (2011) · The Journal of Toxicological Sciences · doi:10.2131/jts.36.515 · Cited by 8 · see citing works
Sonohara, Y., Iwai, S., & Kuraoka, I. (2015) · Genes and Environment · doi:10.1186/s41021-015-0014-8 · Cited by 7 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [14]Bohrson CL Linked-read analysis identifies mutations in single-cell DNA sequencing data bioRxiv 2017 PMC6900933 30886424
- [49]Crabtree GR Our fragile intellect. Part II Trends Genet 29 3 5 2013 23153597
Cited by
Sorted by citations
Clinical and therapeutic relevance of cancer-associated fibroblasts
Chen, Y., McAndrews, K. M., & Kalluri, R. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00546-5 · Cited by 1,230 · see citing works
DNA methylation aging clocks: challenges and recommendations
Bell, C. G., Lowe, R., Adams, P. D., Baccarelli, A. A., Beck, S., Bell, J. T., Christensen, B. C., Gladyshev, V. N., Heijmans, B. T., Horvath, S., et al. (2019) · Genome Biology · doi:10.1186/s13059-019-1824-y · Cited by 1,025 · see citing works
The central role of DNA damage in the ageing process
Schumacher, B., Pothof, J., Vijg, J., & Hoeijmakers, J. H. J. (2021) · Nature · doi:10.1038/s41586-021-03307-7 · Cited by 907 · see citing works
Measuring biological aging in humans: a quest
Ferrucci, L., Gonzalez‐Freire, M., Fabbri, E., Simonsick, E., Tanaka, T., Moore, Z., Salimi, S., Sierra, F., & de Cabo, R. (2020) · Aging Cell · doi:10.1111/acel.13080 · Cited by 781 · see citing works
The landscape of somatic mutation in normal colorectal epithelial cells
Lee-Six, H., Olafsson, S., Ellis, P., Osborne, R. J., Sanders, M. A., Moore, L., Georgakopoulos, N., Torrente, F., Noorani, A., Goddard, M., et al. (2019) · Nature · doi:10.1038/s41586-019-1672-7 · Cited by 747 · see citing works
Population dynamics of normal human blood inferred from somatic mutations
Lee-Six, H., Øbro, N. F., Shepherd, M. S., Grossmann, S., Dawson, K., Belmonte, M., Osborne, R. J., Huntly, B. J. P., Martincorena, I., Anderson, E., et al. (2018) · Nature · doi:10.1038/s41586-018-0497-0 · Cited by 604 · see citing works
The mutational landscape of normal human endometrial epithelium
Moore, L., Leongamornlert, D., Coorens, T. H. H., Sanders, M. A., Ellis, P., Dentro, S. C., Dawson, K. J., Butler, T., Rahbari, R., Mitchell, T. J., et al. (2020) · Nature · doi:10.1038/s41586-020-2214-z · Cited by 499 · see citing works
The genomics of oxidative DNA damage, repair, and resulting mutagenesis
Poetsch, A. R. (2020) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2019.12.013 · Cited by 420 · see citing works
Extensive heterogeneity in somatic mutation and selection in the human bladder
Lawson, A. R. J., Abascal, F., Coorens, T. H. H., Hooks, Y., O’Neill, L., Latimer, C., Raine, K., Sanders, M. A., Warren, A. Y., Mahbubani, K. T. A., et al. (2020) · Science · doi:10.1126/science.aba8347 · Cited by 311 · see citing works
Single-cell sequencing techniques from individual to multiomics analyses
Kashima, Y., Sakamoto, Y., Kaneko, K., Seki, M., Suzuki, Y., & Suzuki, A. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-00499-2 · Cited by 270 · see citing works
Zhang, L., Dong, X., Lee, M., Maslov, A. Y., Wang, T., & Vijg, J. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1902510116 · Cited by 222 · see citing works
Neuronal enhancers are hotspots for DNA single-strand break repair
Wu, W., Kargbo-Hill, S. E., Nathan, W. J., Paiano, J., Callen, E., Wang, D., Shinoda, K., van Wietmarschen, N., Colón-Mercado, J. M., Zong, D., et al. (2021) · Nature · doi:10.1038/s41586-021-03468-5 · Cited by 223 · see citing works
Somatic genomic changes in single Alzheimer’s disease neurons
Miller, M. B., Huang, A. Y., Kim, J., Zhou, Z., Kirkham, S. L., Maury, E. A., Ziegenfuss, J. S., Reed, H. C., Neil, J. E., Rento, L., et al. (2022) · Nature · doi:10.1038/s41586-022-04640-1 · Cited by 223 · see citing works
Pao, P.-C., Patnaik, D., Watson, L. A., Gao, F., Pan, L., Wang, J., Adaikkan, C., Penney, J., Cam, H. P., Huang, W.-C., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16361-y · Cited by 216 · see citing works
Macroscopic somatic clonal expansion in morphologically normal human urothelium
Li, R., Du, Y., Chen, Z., Xu, D., Lin, T., Jin, S., Wang, G., Liu, Z., Lu, M., Chen, X., et al. (2020) · Science · doi:10.1126/science.aba7300 · Cited by 206 · see citing works
Ogrodnik, M., Salmonowicz, H., & Gladyshev, V. N. (2019) · Aging Cell · doi:10.1111/acel.12841 · Cited by 184 · see citing works
Park, J. S., Lee, J., Jung, E. S., Kim, M.-H., Kim, I. B., Son, H., Kim, S., Kim, S., Park, Y. M., Mook-Jung, I., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11000-7 · Cited by 155 · see citing works
Recent advances in single-cell sequencing technologies
Wen, L., & Tang, F. (2022) · Precision Clinical Medicine · doi:10.1093/pcmedi/pbac002 · Cited by 127 · see citing works
Huang, Z., Sun, S., Lee, M., Maslov, A. Y., Shi, M., Waldman, S., Marsh, A., Siddiqui, T., Dong, X., Peter, Y., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01035-w · Cited by 125 · see citing works
Dileep, V., Boix, C. A., Mathys, H., Marco, A., Welch, G. M., Meharena, H. S., Loon, A., Jeloka, R., Peng, Z., Bennett, D. A., et al. (2023) · Cell · doi:10.1016/j.cell.2023.08.038 · Cited by 130 · see citing works
Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease
Welch, G., & Tsai, L. (2022) · The EMBO Reports · doi:10.15252/embr.202154217 · Cited by 129 · see citing works
A NPAS4–NuA4 complex couples synaptic activity to DNA repair
Pollina, E. A., Gilliam, D. T., Landau, A. T., Lin, C., Pajarillo, N., Davis, C. P., Harmin, D. A., Yap, E.-L., Vogel, I. R., Griffith, E. C., et al. (2023) · Nature · doi:10.1038/s41586-023-05711-7 · Cited by 125 · see citing works
Incorporation of a nucleoside analog maps genome repair sites in postmitotic human neurons
Reid, D. A., Reed, P. J., Schlachetzki, J. C. M., Nitulescu, I. I., Chou, G., Tsui, E. C., Jones, J. R., Chandran, S., Lu, A. T., McClain, C. A., et al. (2021) · Science · doi:10.1126/science.abb9032 · Cited by 121 · see citing works
Brazhnik, K., Sun, S., Alani, O., Kinkhabwala, M., Wolkoff, A. W., Maslov, A. Y., Dong, X., & Vijg, J. (2020) · Science Advances · doi:10.1126/sciadv.aax2659 · Cited by 114 · see citing works
Somatic Mutagenesis in Mammals and Its Implications for Human Disease and Aging
Zhang, L., & Vijg, J. (2018) · Annual Review of Genetics · doi:10.1146/annurev-genet-120417-031501 · Cited by 108 · see citing works
Luquette, L. J., Miller, M. B., Zhou, Z., Bohrson, C. L., Zhao, Y., Jin, H., Gulhan, D., Ganz, J., Bizzotto, S., Kirkham, S., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01180-2 · Cited by 108 · see citing works
Self-citationSomatic variants in autosomal dominant genes are a rare cause of sporadic Alzheimer’s disease
Nicolas, G., Acuña‐Hidalgo, R., Keogh, M. J., Quenez, O., Steehouwer, M., Lelieveld, S., Rousseau, S., Richard, A., Oud, M. S., Marguet, F., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.06.3056 · Cited by 81 · see citing works
High prevalence of focal and multi-focal somatic genetic variants in the human brain
Keogh, M. J., Wei, W., Aryaman, J., Walker, L., van den Ameele, J., Coxhead, J., Wilson, I., Bashton, M., Beck, J., West, J., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06331-w · Cited by 74 · see citing works
Lodato, M. A., & Walsh, C. A. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz191 · Cited by 56 · see citing works
Self-citationTemporal changes in the gene expression heterogeneity during brain development and aging
Işıldak, U., Somel, M., Thornton, J. M., & Dönertaş, H. M. (2020) · Scientific Reports · doi:10.1038/s41598-020-60998-0 · Cited by 53 · see citing works
Exercise-induced AMPK activation is involved in delay of skeletal muscle senescence
Yoon, K. J., Zhang, D., Kim, S.-J., Lee, M.-C., & Moon, H. Y. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.03.086 · Cited by 44 · see citing works
Histone Deacetylases 1 and 2 in Memory Function
Pao, P.-C., & Tsai, L.-H. (2022) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.1c00775 · Cited by 34 · see citing works
Analyzing somatic mutations by single-cell whole-genome sequencing
Zhang, L., Lee, M., Maslov, A. Y., Montagna, C., Vijg, J., & Dong, X. (2024) · Nature Protocols · doi:10.1038/s41596-023-00914-8 · Cited by 26 · see citing works
Lung transcriptomic clock predicts premature aging in cigarette smoke-exposed mice
Choukrallah, M.-A., Hoeng, J., Peitsch, M. C., & Martin, F. (2020) · BMC Genomics · doi:10.1186/s12864-020-6712-z · Cited by 27 · see citing works
Zhu, Q., Niu, Y., Gundry, M., & Zong, C. (2021) · Science Advances · doi:10.1126/sciadv.abf3329 · Cited by 18 · see citing works
Huang, A. Y., Zhou, Z., Talukdar, M., Enyenihi, L., Miller, M. B., Chhouk, B., Rosen, I., Zheng, M., Zhou, M., Yang, A., et al. (2026) · Cell · doi:10.1016/j.cell.2026.03.040 · Cited by 15 · see citing works
Self-citationRen, P., Zheng, C., Pang, Y., Qiang, Y., Sun, S., Wang, Q., Xu, W., Lee, M., Lu, Z., Zhou, M., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-01011-z · Cited by 6 · see citing works
Uncovering the signatures of aging and senescence in the human dorsolateral prefrontal cortex
Sloan, N. X., Mares, J., Daly, A. C., Grier, S., Haq, I., Jackson, C. A., Barretto, N., Casel, O., Kang, K., Khiste, S., et al. (2026) · Cell Genomics · doi:10.1016/j.xgen.2025.101127 · Cited by 2 · see citing works
- Authors
- Lodato, M. A., Rodin, R. E., Bohrson, C. L., Coulter, M. E., Barton, A. R., Kwon, M., Sherman, M. A., Vitzthum, C. M., Luquette, L. J., Yandava, C. N., Yang, P., Chittenden, T. W., Hatem, N. E., Ryu, S. C., Woodworth, M. B., Park, P. J., & Walsh, C. A.
- Affiliations
- Broad Institute (US)
- Harvard University (US)
- Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
- Computational Statistics and Bioinformatics Group, Advanced Artificial Intelligence Research Laboratory, WuXi NextCODE, Cambridge, MA, USA.
- Boston Children's Hospital (US)
- Cañada College (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Park, Peter J.
- Walsh, Christopher A.
- ORCID
- Venue
- Science
- Published
- 2018-02-02
- Volume
- 359
- Issue
- 6375
- Pages
- 555-559
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC5831169
- OpenAlex
- W2774506962
- Cited by
- 635
- References
- 48
- Citations by year
- 2026: 45 · 2025: 62 · 2024: 56 · 2023: 68 · 2022: 77 · 2021: 85 · 2020: 123 · 2019: 71 · 2018: 44 · 2017: 4
- FWCI
- 28.18
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Science (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute (N/A)
- National Institute of Mental Health (F30 MH102909, U01MH106883, P50MH106933, U01 MH106883)
- National Institute on Aging (K99 AG054749 01)
- National Human Genome Research Institute (T32HG002295)
- National Center for Research Resources (1S10RR028832-01)
- Harvard Ludwig Center (N/A)
- Paul G. Allen Family Foundation (N/A)
- National Institute of Neurological Disorders and Stroke (R01 NS032457, R01 NS079277)
- Manton Center for Orphan Disease Research (N/A)
- National Institute of General Medical Sciences (T32GM007753)
- Stuart H.Q. and Victoria Quan Foundation (Fellowship in Neurobiology)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- somatic mutations, single neurons, aging, neurodegeneration, single nucleotide variants, Cockayne syndrome, xeroderma pigmentosum, DNA repair disorders, prefrontal cortex, hippocampus
- MeSH terms
- Whole Genome Sequencing, Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Aging, Child, Child, Preschool, Cockayne Syndrome, DNA Mutational Analysis, DNA Repair, Female, Hippocampus, Humans, Infant, Male, Middle Aged, Neurons, Xeroderma Pigmentosum, Prefrontal Cortex, Neurodegenerative Diseases, Neurogenesis, Young Adult, Single-Cell Analysis, Mutation Rate
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
