Single-Cell Profiling Across Immune Tissues and Organs Reveals Immunosenescence Signatures in Male Rhesus Monkeys

Area of Science:

• Immunology
• Gerontology
• Genomics

Background:

• Immune system function declines with age (immunosenescence).
• Systemic immune aging features across primate organs are not well understood.
• Non-human primates offer valuable models for studying human aging.

Purpose of the Study:

• To characterize age-related immune system changes in rhesus monkeys at a single-cell level.
• To identify potential biomarkers of immunosenescence.
• To explore tissue-specific and cell-type-specific alterations in aging immune cells.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) of bone marrow, spleen, lymph nodes, and peripheral blood.
• Transcriptional profiling of immune cells from young and aged male rhesus monkeys.
• Gene regulatory network analysis to identify key transcription factors.

Main Results:

• Extensive transcriptional remodeling observed across all sampled immune tissues.
• Upregulation of Granzyme B (GZMB) in aged monkeys suggests it as an immunosenescence biomarker.
• Identification of BHLHE40 as a key transcription factor in aging CD8+ T cells.
• Age-associated expansion of dysfunctional CD8+ central memory T cells.
• Decline in a specific naive B cell population in aged bone marrow, potentially impacting humoral immunity.

Conclusions:

• Provides a comprehensive single-cell atlas of immune aging in non-human primates.
• Reveals cell-type and tissue-specific immune aging mechanisms.
• Highlights GZMB and BHLHE40 as potential targets for future research and biomarker development in human aging.