Profiling the transcriptomic age of single-cells in humans

Area of Science:

• Genomics and Bioinformatics
• Cellular and Molecular Biology
• Aging Research

Background:

• Organismal aging clocks are established, but cellular aging clocks, especially in humans, are underdeveloped.
• Previous single-cell omics clocks were primarily developed in mice, leaving a gap in human cellular age profiling.
• Understanding cellular aging is crucial for comprehending organismal aging and age-related diseases.

Purpose of the Study:

• To develop and validate single-cell transcriptomic clocks for predicting the age of human blood cells.
• To investigate the relationship between transcriptomic age and cellular senescence.
• To explore the impact of COVID-19 on cellular transcriptomic age across different blood cell types.
• To examine transcriptomic age dynamics during early human embryonic development.

Main Methods:

• Utilized a large dataset of single-cell RNA sequencing (scRNA-seq) data from 1,058,909 blood cells of 508 healthy human donors (aged 19-75).
• Developed cell-type-specific single-cell transcriptomic clocks.
• Applied these clocks to analyze transcriptomic age in relation to cellular senescence, COVID-19 status, and embryonic development stages.

Main Results:

• Transcriptomic age significantly correlates with markers of cellular senescence.
• Moderate COVID-19 is associated with decreased transcriptomic age in classical monocytes, naive B cells, and T cells, with potential increases in severe cases.
• Human embryonic cells exhibit transcriptomic rejuvenation at the morulae and blastocyst stages.

Conclusions:

• Single-cell transcriptomic clocks are effective tools for assessing cellular aging in humans.
• These clocks provide insights into the cellular aging process, its modulation by disease (COVID-19), and developmental changes.
• The findings highlight the potential of single-cell transcriptomic clocks for studying aging and rejuvenation at the cellular level.