The sculpting of somatic mutational landscapes by evolutionary forces and their impacts on aging‐related disease
Aging represents the major risk factor for the development of cancer and many other diseases. Recent findings show that normal tissues become riddled with expanded clones that are frequently driven by cancer‐associated mutations in an aging‐dependent fashion. Additional studies show how aged tissue...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-09-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.13275 |
| _version_ | 1811183664299507712 |
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| author | Fabio Marongiu James DeGregori |
| author_facet | Fabio Marongiu James DeGregori |
| author_sort | Fabio Marongiu |
| collection | DOAJ |
| description | Aging represents the major risk factor for the development of cancer and many other diseases. Recent findings show that normal tissues become riddled with expanded clones that are frequently driven by cancer‐associated mutations in an aging‐dependent fashion. Additional studies show how aged tissue microenvironments promote the initiation and progression of malignancies, while young healthy tissues actively suppress the outgrowth of malignant clones. Here, we discuss conserved mechanisms that eliminate poorly functioning or potentially malignant cells from our tissues to maintain organismal health and fitness. Natural selection acts to preserve tissue function and prevent disease to maximize reproductive success but these mechanisms wane as reproduction becomes less likely. The ensuing age‐dependent tissue decline can impact the shape and direction of clonal somatic evolution, with lifestyle and exposures influencing its pace and intensity. We also consider how aging‐ and exposure‐dependent clonal expansions of “oncogenic” mutations might both increase cancer risk late in life and contribute to tissue decline and non‐malignant disease. Still, we can marvel at the ability of our bodies to avoid cancers and other diseases despite the accumulation of billions of cells with cancer‐associated mutations. |
| first_indexed | 2024-04-11T09:50:34Z |
| format | Article |
| id | doaj.art-4b794a98bd4d4e10a91080afb90bc231 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-04-11T09:50:34Z |
| publishDate | 2022-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-4b794a98bd4d4e10a91080afb90bc2312022-12-22T04:30:48ZengWileyMolecular Oncology1574-78911878-02612022-09-0116183238325810.1002/1878-0261.13275The sculpting of somatic mutational landscapes by evolutionary forces and their impacts on aging‐related diseaseFabio Marongiu0James DeGregori1Department of Biochemistry and Molecular Genetics University of Colorado Anschutz Medical Campus Aurora CO USADepartment of Biochemistry and Molecular Genetics University of Colorado Anschutz Medical Campus Aurora CO USAAging represents the major risk factor for the development of cancer and many other diseases. Recent findings show that normal tissues become riddled with expanded clones that are frequently driven by cancer‐associated mutations in an aging‐dependent fashion. Additional studies show how aged tissue microenvironments promote the initiation and progression of malignancies, while young healthy tissues actively suppress the outgrowth of malignant clones. Here, we discuss conserved mechanisms that eliminate poorly functioning or potentially malignant cells from our tissues to maintain organismal health and fitness. Natural selection acts to preserve tissue function and prevent disease to maximize reproductive success but these mechanisms wane as reproduction becomes less likely. The ensuing age‐dependent tissue decline can impact the shape and direction of clonal somatic evolution, with lifestyle and exposures influencing its pace and intensity. We also consider how aging‐ and exposure‐dependent clonal expansions of “oncogenic” mutations might both increase cancer risk late in life and contribute to tissue decline and non‐malignant disease. Still, we can marvel at the ability of our bodies to avoid cancers and other diseases despite the accumulation of billions of cells with cancer‐associated mutations.https://doi.org/10.1002/1878-0261.13275agingclonal hematopoiesislife‐history theoryNOTCH1p53somatic evolution |
| spellingShingle | Fabio Marongiu James DeGregori The sculpting of somatic mutational landscapes by evolutionary forces and their impacts on aging‐related disease Molecular Oncology aging clonal hematopoiesis life‐history theory NOTCH1 p53 somatic evolution |
| title | The sculpting of somatic mutational landscapes by evolutionary forces and their impacts on aging‐related disease |
| title_full | The sculpting of somatic mutational landscapes by evolutionary forces and their impacts on aging‐related disease |
| title_fullStr | The sculpting of somatic mutational landscapes by evolutionary forces and their impacts on aging‐related disease |
| title_full_unstemmed | The sculpting of somatic mutational landscapes by evolutionary forces and their impacts on aging‐related disease |
| title_short | The sculpting of somatic mutational landscapes by evolutionary forces and their impacts on aging‐related disease |
| title_sort | sculpting of somatic mutational landscapes by evolutionary forces and their impacts on aging related disease |
| topic | aging clonal hematopoiesis life‐history theory NOTCH1 p53 somatic evolution |
| url | https://doi.org/10.1002/1878-0261.13275 |
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