Decoding and rejuvenating human ageing genomes: Lessons from mosaic chromosomal alterations

Area of Science:

• Genomics
• Cell Biology
• Aging Research

Background:

• Genetic mosaicism is prevalent in human aging genomes.
• Mosaic chromosomal alterations (mCAs) have significant functional consequences, impacting numerous genes simultaneously.
• mCAs are linked to age-related diseases such as cancer, Alzheimer's, and cardiovascular disease.

Purpose of the Study:

• To provide a comprehensive overview of mosaic chromosomal alterations (mCAs) in aging genomes.
• To explore the landscapes, causes, consequences, and rejuvenation of mCAs across various scales.
• To highlight the potential of studying mCAs for understanding human aging and disease.

Main Methods:

• Review of cytogenetic, genetic, and genomic studies.
• Analysis of data from cell studies, animal models (flies, mice), and large human cohorts.
• Comprehensive decoding of aging genomes with a focus on mCAs.

Main Results:

• Mosaic chromosomal alterations (mCAs) are a dominant feature of aging genomes.
• mCAs have profound effects on human aging and disease etiology due to widespread gene variation.
• Data from diverse studies reveal the multi-scale impact of mCAs.

Conclusions:

• Detailed study of mCAs in aging genomes is crucial for understanding human aging.
• mCAs can accelerate risk stratification for age-related diseases, especially cancers.
• Insights into mCAs may lead to novel strategies for rejuvenating human aging.