Hand in hand: intrinsic and extrinsic drivers of aging and clonal hematopoiesis

Autor: Jennifer J. Trowbridge, Jennifer M. SanMiguel, Kira Young
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Cancer Research
Aging
Somatic cell
ved/biology.organism_classification_rank.species
DNA Methyltransferase 3A
Mice
0302 clinical medicine
Bone Marrow
Selective advantage
Myeloid Cells
DNA (Cytosine-5-)-Methyltransferases
Stem Cell Niche
Cellular Senescence
Feedback
Physiological
Clonal hematopoiesis
Hematopoietic stem cell
hemic and immune systems
Hematology
Phenotype
Chromatin
medicine.anatomical_structure
030220 oncology & carcinogenesis
Female
Context (language use)
Antineoplastic Agents
Biology
Article
03 medical and health sciences
Genetics
medicine
Animals
Humans
Selection
Genetic
Model organism
Molecular Biology
Inflammation
ved/biology
Cell Biology
DNA Methylation
Hematopoietic Stem Cells
Clone Cells
Hematopoiesis
030104 developmental biology
Mutation
Bone marrow
Neuroscience
DNA Damage
Forecasting
Zdroj: Exp Hematol
ISSN: 1873-2399
Popis: Over the past 25 years, the importance of hematopoietic stem cell (HSC) aging in overall hematopoietic and immune system health span has been appreciated. Much work has been done in model organisms to understand the intrinsic dysregulation that occurs in HSCs during aging, with the goal of identifying modifiable mechanisms that represent the proverbial "fountain of youth." Much more recently, the discovery of somatic mutations that are found to provide a selective advantage to HSCs and accumulate in the hematopoietic system during aging, termed clonal hematopoiesis (CH), inspires revisiting many of these previously defined drivers of HSC aging in the context of these somatic mutations. To truly understand these processes and develop a holistic picture of HSC aging, ongoing and future studies must include investigation of the critical changes that occur in the HSC niche or bone marrow microenvironment with aging, as increasing evidence supports that these HSC-extrinsic alterations provide necessary inflammation, signaling pathway activation or repression, and other selective pressures to favor HSC aging-associated phenotypes and CH. Here, we provide our perspectives based on the past 8 years of our own laboratory's investigations into these mechanisms and chart a path for integrative studies that, in our opinion, will provide an ideal opportunity to discover HSC and hematopoietic health span-extending interventions. This path includes examining when and how aging-associated HSC-intrinsic and HSC-extrinsic changes accumulate over time in different individuals and developing new models to track and test relevant HSC-extrinsic changes, complementary to innovative HSC lineage tracing systems that have recently been developed.
Databáze: OpenAIRE
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