Introduction: Aging is characterized by the progressive loss of physiological capacity. Changes in gene expression can alter activity in defined age-related molecular pathways leading to cellular aging and increased aging disease susceptibility. The aim of the current study was to evaluate whether hyperbaric oxygen therapy (HBOT) affects gene expression in normal, non-pathological, aging adults.

Methods: Thirty-five healthy independently living adults, aged 64 and older, were enrolled to receive 60 daily HBOT exposures. Whole blood samples were collected at baseline, at the 30th and 60th HBOT session, and 1–2 weeks following the last session. Differential gene expression analysis was performed.

Results: Following 60 sessions of HBOT, 1342 genes and 570 genes were differently up- and downregulated (1912 total), respectively (p < 0.01 FDR), compared to baseline. Out of which, five genes were downregulated with a >1.5-fold change: ABCA13 (FC = −2.28), DNAJ6 (FC = −2.16), HBG2 (FC = −1.56), PDXDC1 (FC = −1.53), RANBP17 (FC = −1.75). Two weeks post-HBOT, ABCA13 expression was significantly downregulated with a >1.5fold change (FC = −1.54, p = 0.008).

In conclusion, for the first time in humans, the study provides direct evidence of HBOT is associated with transcriptome changes in whole-blood samples. Our results demonstrate significant changes in gene expression of normal aging population.