Mitigating age-related somatic mutation burden

Jan Vijg; Björn Schumacher; Abdulkadir Abakir; Michael Antonov; Chris Bradley; Alex Cagan; George Church; Vadim N Gladyshev; Vera Gorbunova; Alexander Y Maslov; Wolf Reik; Samim Sharifi; Yousin Suh; Kenneth Walsh

doi:10.1016/j.molmed.2023.04.002

Mitigating age-related somatic mutation burden

Trends Mol Med. 2023 Jul;29(7):530-540. doi: 10.1016/j.molmed.2023.04.002. Epub 2023 Apr 29.

Authors

Jan Vijg¹, Björn Schumacher², Abdulkadir Abakir³, Michael Antonov⁴, Chris Bradley⁵, Alex Cagan⁶, George Church⁷, Vadim N Gladyshev⁸, Vera Gorbunova⁹, Alexander Y Maslov¹⁰, Wolf Reik¹¹, Samim Sharifi⁵, Yousin Suh¹², Kenneth Walsh¹³

Affiliations

¹ Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Center for Single-Cell Omics, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: jan.vijg@einsteinmed.edu.
² Institute for Genome Stability in Aging and Disease, University and University Hospital of Cologne, Cologne, Germany; Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany. Electronic address: bjoern.schumacher@uni-koeln.de.
³ Altos Labs Cambridge Institute of Science, Granta Park, Cambridge, UK.
⁴ Formic Ventures, San Francisco, CA 94107, USA.
⁵ Matter Bioworks, Brooklyn, NY 11237, USA.
⁶ Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.
⁷ Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
⁸ Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
⁹ Department of Biology, University of Rochester, Rochester, NY 14627, USA.
¹⁰ Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
¹¹ Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK; Epigenetics Programme, Babraham Institute, Cambridge, CB22 3AT, UK; Altos Labs Cambridge Institute of Science, Granta Park, Cambridge, UK; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK; Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.
¹² Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, NY, USA; Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
¹³ Hematovascular Biology Center, Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.

PMID: 37121869
DOI: 10.1016/j.molmed.2023.04.002

Abstract

Genomes are inherently unstable and require constant DNA repair to maintain their genetic information. However, selective pressure has optimized repair mechanisms in somatic cells only to allow transmitting genetic information to the next generation, not to maximize sequence integrity long beyond the reproductive age. Recent studies have confirmed that somatic mutations, due to errors during genome repair and replication, accumulate in tissues and organs of humans and model organisms. Here, we describe recent advances in the quantitative analysis of somatic mutations in vivo. We also review evidence for or against a possible causal role of somatic mutations in aging. Finally, we discuss options to prevent, delay or eliminate de novo, random somatic mutations as a cause of aging.

Keywords: aging; cancer; chromatin organization; clonal hematopoiesis; germline versus somatic genome; somatic mutations.

Publication types

Review

MeSH terms

Aging* / genetics
DNA Repair*
Genome
Humans
Mutation

Grants and funding

P01 AG047200/AG/NIA NIH HHS/United States