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Clonal hematopoiesis, somatic mosaicism, and age-associated disease.
Evans, Megan A; Walsh, Kenneth.
Afiliación
  • Evans MA; Hematovascular Biology Center, Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia.
  • Walsh K; Hematovascular Biology Center, Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia.
Physiol Rev ; 103(1): 649-716, 2023 01 01.
Article en En | MEDLINE | ID: mdl-36049115
ABSTRACT
Somatic mosaicism, the occurrence of multiple genetically distinct cell clones within the same tissue, is an evitable consequence of human aging. The hematopoietic system is no exception to this, where studies have revealed the presence of expanded blood cell clones carrying mutations in preleukemic driver genes and/or genetic alterations in chromosomes. This phenomenon is referred to as clonal hematopoiesis and is remarkably prevalent in elderly individuals. While clonal hematopoiesis represents an early step toward a hematological malignancy, most individuals will never develop blood cancer. Somewhat unexpectedly, epidemiological studies have found that clonal hematopoiesis is associated with an increase in the risk of all-cause mortality and age-related disease, particularly in the cardiovascular system. Studies using murine models of clonal hematopoiesis have begun to shed light on this relationship, suggesting that driver mutations in mature blood cells can causally contribute to aging and disease by augmenting inflammatory processes. Here we provide an up-to-date review of clonal hematopoiesis within the context of somatic mosaicism and aging and describe recent epidemiological studies that have reported associations with age-related disease. We will also discuss the experimental studies that have provided important mechanistic insight into how driver mutations promote age-related disease and how this knowledge could be leveraged to treat individuals with clonal hematopoiesis.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Enfermedades Cardiovasculares / Hematopoyesis Tipo de estudio: Risk_factors_studies Límite: Aged / Animals / Humans Idioma: En Revista: Physiol Rev Año: 2023 Tipo del documento: Article

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Enfermedades Cardiovasculares / Hematopoyesis Tipo de estudio: Risk_factors_studies Límite: Aged / Animals / Humans Idioma: En Revista: Physiol Rev Año: 2023 Tipo del documento: Article