Single-Cell Transcriptomics Reveals Longevity Immune Remodeling Features Shared by Centenarians and Their Offspring

Area of Science:

• Immunology
• Gerontology
• Genomics

Background:

• Centenarians serve as a model for healthy aging, exhibiting fewer infections and tumors.
• Immune system characteristics associated with longevity remain incompletely understood due to a lack of suitable control groups.

Purpose of the Study:

• To investigate shared immune features between centenarians (CEN) and their offspring (CO).
• To identify immune system adaptations contributing to healthy aging.

Main Methods:

• Single-cell transcriptomic analysis of peripheral blood mononuclear cells (PBMCs).
• Comparison of immune cell populations between centenarians, their offspring, and age-matched controls.

Main Results:

• Both centenarians and offspring show depleted naive phenotype clusters (NPC) and increased cytotoxic phenotype clusters (CPC), primarily CD8+ T cells, compared to controls.
• Cytotoxic T cells in centenarians and offspring display enhanced immune response pathways and similar T-cell receptor features, including high clonal expansion.
• Centenarians accumulate GZMB+ and CMC1+ CD8 T cells, differing from typical aging patterns.

Conclusions:

• Healthy aging is associated with immune remodeling, characterized by an increase in both the quantity and function of cytotoxic T cells.
• The observed immune profile in centenarians and their offspring suggests a conserved mechanism for enhanced immunity and healthy longevity.