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The sculpting of somatic mutational landscapes by evolutionary forces and their impacts on aging‐related disease
by
DeGregori, James
, Marongiu, Fabio
in
Age
/ Aging
/ Animal reproduction
/ Breeding success
/ Cancer
/ Cardiovascular disease
/ clonal hematopoiesis
/ Cloning
/ Epigenetics
/ Evolution
/ Kinases
/ Laboratory animals
/ Leukemia
/ life‐history theory
/ Microenvironments
/ Mortality
/ Mutation
/ Natural selection
/ NOTCH1
/ Older people
/ p53
/ Proteins
/ Reproductive fitness
/ Risk factors
/ Sarcoma
/ Senescence
/ somatic evolution
/ Stem cells
/ Success
2022
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The sculpting of somatic mutational landscapes by evolutionary forces and their impacts on aging‐related disease
by
DeGregori, James
, Marongiu, Fabio
in
Age
/ Aging
/ Animal reproduction
/ Breeding success
/ Cancer
/ Cardiovascular disease
/ clonal hematopoiesis
/ Cloning
/ Epigenetics
/ Evolution
/ Kinases
/ Laboratory animals
/ Leukemia
/ life‐history theory
/ Microenvironments
/ Mortality
/ Mutation
/ Natural selection
/ NOTCH1
/ Older people
/ p53
/ Proteins
/ Reproductive fitness
/ Risk factors
/ Sarcoma
/ Senescence
/ somatic evolution
/ Stem cells
/ Success
2022
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Do you wish to request the book?
The sculpting of somatic mutational landscapes by evolutionary forces and their impacts on aging‐related disease
by
DeGregori, James
, Marongiu, Fabio
in
Age
/ Aging
/ Animal reproduction
/ Breeding success
/ Cancer
/ Cardiovascular disease
/ clonal hematopoiesis
/ Cloning
/ Epigenetics
/ Evolution
/ Kinases
/ Laboratory animals
/ Leukemia
/ life‐history theory
/ Microenvironments
/ Mortality
/ Mutation
/ Natural selection
/ NOTCH1
/ Older people
/ p53
/ Proteins
/ Reproductive fitness
/ Risk factors
/ Sarcoma
/ Senescence
/ somatic evolution
/ Stem cells
/ Success
2022
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The sculpting of somatic mutational landscapes by evolutionary forces and their impacts on aging‐related disease
Journal Article
The sculpting of somatic mutational landscapes by evolutionary forces and their impacts on aging‐related disease
2022
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Overview
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. Pathogenic clonal expansions can promote and be promoted by inflammation, and contribute to multiple diseases of aging. While these clones can sometimes directly contribute to malignant disease, as clearly demonstrated for leukemias with clonal hematopoiesis mutations, evidence also reveals how clonal expansions can contribute indirectly to cancers and non‐malignant diseases such as through the promotion of inflammation.
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