Decoding and rejuvenating human ageing genomes: Lessons from mosaic chromosomal alterations.
Ageing Res Rev
; 68: 101342, 2021 07.
Article
en En
| MEDLINE
| ID: mdl-33866012
One of the most curious findings emerged from genome-wide studies over the last decade was that genetic mosaicism is a dominant feature of human ageing genomes. The clonal dominance of genetic mosaicism occurs preceding the physiological and physical ageing and associates with propensity for diseases including cancer, Alzheimer's disease, cardiovascular disease and diabetes. These findings are revolutionizing the ways biologists thinking about health and disease pathogenesis. Among all mosaic mutations in ageing genomes, mosaic chromosomal alterations (mCAs) have the most significant functional consequences because they can produce intercellular genomic variations simultaneously involving dozens to hundreds or even thousands genes, and therefore have most profound effects in human ageing and disease etiology. Here, we provide a comprehensive picture of the landscapes, causes, consequences and rejuvenation of mCAs at multiple scales, from cell to human population, by reviewing data from cytogenetic, genetic and genomic studies in cells, animal models (fly and mouse) and, more frequently, large-cohort populations. A detailed decoding of ageing genomes with a focus on mCAs may yield important insights into the genomic architecture of human ageing, accelerate the risk stratification of age-related diseases (particularly cancers) and development of novel targets and strategies for delaying or rejuvenating human (genome) ageing.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Mosaicismo
/
Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Ageing Res Rev
Asunto de la revista:
GERIATRIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Reino Unido