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A Pathogen Penalty? Associations Between Persistent Infections and Biological Aging in the US

Jennifer Momkus1,2, Kathleen Mullan Harris2,3, Jessie K Edwards1,2

  • 1Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

The Journal of Infectious Diseases
|December 10, 2025
PubMed
Abstract

Insights

Persistent infections like cytomegalovirus (CMV) accelerate biological aging and immune system decline even in early adulthood. This study links CMV and other infections to epigenetic aging and immunosenescence markers.

Area of Science:

  • Gerontology
  • Immunology
  • Infectious Diseases

Background:

  • Persistent infections, including cytomegalovirus (CMV), herpes simplex virus type 1 (HSV-1), Epstein-Barr Virus (EBV), and Helicobacter pylori (H. pylori), cause chronic immune stimulation.
  • These infections may contribute to biological aging, but associations earlier in adulthood are less understood.

Purpose of the Study:

  • To examine the associations between common persistent infections and markers of biological aging in young adulthood.
  • To investigate the impact of CMV, HSV-1, EBV, and H. pylori on epigenetic age acceleration and cellular immunosenescence.

Main Methods:

  • Utilized data from a nationally representative U.S. cohort, assessing infections at a median age of 28 years.
  • Measured epigenetic age acceleration (EAA) using GrimAge, PhenoAge, and DunedinPACE clocks.
  • Assessed cellular immunosenescence via DNA methylation-based immune cell ratios approximately 10 years later.

Main Results:

  • Cytomegalovirus (CMV) infection was consistently linked to accelerated epigenetic aging and increased cellular immunosenescence.
  • CMV seropositivity correlated with a higher CD4+ memory to naive cell ratio.
  • Epstein-Barr Virus (EBV) and H. pylori showed notable associations with EAA, while H. pylori was unexpectedly linked to a higher CD4+/CD8+ cell ratio.

Conclusions:

  • Persistent infections, especially CMV, significantly influence biological aging through DNA methylation changes and immunosenescence prior to midlife.
  • Further research is required to understand the life-course impact of infection timing and burden on aging and immune function.
Keywords:
agingcytomegalovirusepigenetic age accelerationimmunosenescencepersistent infections

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