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Variations in Innate Immune Cell Subtypes Correlate with Epigenetic Clocks, Inflammaging and Health Outcomes.

Xiaolong Guo1, Josephine A Robertson2, Andrea Aparicio3

  • 1Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|August 27, 2025
PubMed
Summary
This summary is machine-generated.

Innate immune cell shifts and nucleated red blood cells impact biological age estimates from epigenetic clocks. This finding expands understanding of blood cell heterogeneity

Keywords:
DNA methylationaging Biomarkersepigenetic clockshealth outcomesinflammaginginnate immune system

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Area of Science:

  • Immunology
  • Gerontology
  • Epigenetics

Background:

  • Epigenetic clocks in blood estimate biological age and correlate with mortality.
  • Previous research focused on adaptive immune system heterogeneity's effect on epigenetic clocks.
  • The impact of innate immune system heterogeneity on epigenetic clocks remains largely unexplored.

Purpose of the Study:

  • To investigate how heterogeneity within innate immune cells affects epigenetic clock estimates.
  • To explore associations between innate immune cell shifts, inflammaging, and all-cause mortality.
  • To examine the role of nucleated red blood cell-like cells in health outcomes.

Main Methods:

  • Utilized a high-resolution DNA methylation reference panel of 19 immune cell types.
  • Included young and adult subsets of monocytes, natural killer cells, and neutrophils.
  • Validated monocyte heterogeneity associations with inflammation using transcriptomic and metabolomic data.

Main Results:

  • Shifts in innate immune cell subtypes (monocytes, NK, neutrophils) correlate with epigenetic clock acceleration and inflammaging.
  • Monocyte heterogeneity is linked to inflammation, validated by multi-omics data.
  • Nucleated red blood cell-like cells associate with inflammaging, erythropoiesis dysfunction, and are a major mortality risk factor.

Conclusions:

  • Innate immune cell heterogeneity, beyond the adaptive immune system, influences epigenetic clock accuracy.
  • Heterogeneity in innate immune and erythrocyte-like cells is associated with inflammaging and mortality.
  • Findings highlight the broader impact of blood cell composition on biological aging and health outcomes.