Hyperbaric oxygen therapy modulates immune aging in a personalized manner: a linear mixed-effects analysis

Immunosenescence, characterized by telomere shortening, senescence-associated T-cell subsets, and chronic inflammation, is a hallmark of biological aging. Whether these aging-related immune biomarkers can be modulated through short-term intervention and whether responses differ according to individual characteristics remain unclear. This study evaluated the effects of short-term hyperbaric oxygen therapy (HBOT) on senescence-related biomarkers and explored factors associated with individual responsiveness.

In a prospective cohort study, participants underwent 30 HBOT sessions (2.5 ATA, 100% oxygen, 60 min per session). Relative telomere length (2^-ΔΔCt) and proportions of senescence-associated T-cell phenotypes (CD28⁻/CD27⁻ CD4⁺ or CD8⁺ T cells) were assessed in peripheral blood mononuclear cells (PBMCs), while plasma concentrations (pg/mL) of inflammatory cytokines, including pro-inflammatory cytokines (TNF-α and IL-1β) and the anti-inflammatory cytokine IL-10, were quantified using multiplex bead-based immunoassays at baseline and after 10, 20, and 30 sessions. Linear mixed-effects models were used to evaluate longitudinal HBOT-associated changes and interactions with age, sex, and BMI.

In this clinically heterogeneous cohort comprising apparently healthy individuals and patients receiving HBOT for clinical indications, HBOT was associated with a significant, time-dependent increase in relative telomere length (up to + 29.0% after 30 sessions; p < 0.001, Cohen's d = 0.70) and reduced proportions of senescence-associated T-cell phenotypes, particularly within CD8⁺ T-cell subsets. TNF-α, IL-1β, and IL-10 did not show significant overall time-dependent changes across the cohort. However, subgroup analyses suggested that HBOT-associated responses varied according to age, sex, and BMI: younger (20-39 years) and middle-aged adults (40-59 years), females, and individuals with normal BMI exhibited greater reductions in senescence-associated T-cell phenotypes, whereas middle-aged groups, males showed significant reductions in inflammatory cytokines after 10 sessions.

Short-term HBOT was associated with changes in multiple immunosenescence-related biomarkers, including increased relative telomere length, reduced proportions of senescence-associated T-cell phenotypes, and dynamic modulation of circulating inflammatory profiles. These responses were heterogeneous and influenced by demographic and metabolic factors, suggesting potential differences in individual HBOT responsiveness. These findings indicate that HBOT may modulate selected markers of immune aging; however, further controlled studies are required to determine the durability, clinical relevance, and mechanisms underlying these effects. This study was registered in the Chinese Clinical Trial Registry (ChiCTR2500110103).