Exercise and inflammatory cytokine regulation among older adults with myeloid malignancies

• DOI: 10.1016/j.exger.2024.112364
• Publication Date: 2024-01-25T13:22:13Z
• Authors: Kah Poh Loh; Ying Wang; Chandrika Sanapala; Nikesha Gilmore; Colleen Netherby-...; Jason H. Mendler; Jane Liesveld; Eric Huselton; AnnaLynn M. Williams; Heidi D. Klepin; Marielle Jensen-B...; Karen Mustian; Paula Vertino; Martha Susiarjo; Michelle C. Janel...
• Keywords: Inflammation; DNA methylation; QH301-705.5; Myeloid malignancies; R; Article; 03 medical and health sciences; 0302 clinical medicine; Cytokines; Medicine; Mobile health; Biology (General); Exercise

Tumor necrosis factor (TNF)α is a major regulator of inflammation. However, the epigenetic regulation of TNFα in the context of an exercise intervention among older adults with cancer is understudied. In this exploratory analysis, we used data from a single-arm mobile health (mHealth) exercise intervention among older adults with myeloid malignancies to 1) assess changes in TNFα promoter methylation, TNFα mRNA expression, serum TNFα and other related-cytokine levels after intervention; and 2) assess correlations between blood markers and exercise levels. Twenty patients were included. From baseline to post-intervention, there was no statistical changes in TNFα promoter methylation status at seven CpG sites, TNFα mRNA expression, and serum TNFα levels. Effect sizes, however, were moderate to large for several CpG sites (-120, -147, -162, and -164; Cohen's d = 0.44-0.75). Median serum TNFα sR1 levels (83.63, IQR 130.58, p = 0.06; Cohen's d = 0.18) increased but not the other cytokines. Increases in average daily steps were correlated with increases in TNFα promoter methylation at CpG sites -147 (r = 0.48; p = 0.06) and -164 (r = 0.51; p = 0.04). Resistance training minutes were negatively correlated with TNFα promoter methylation at CpG site -120 (r = -0.62; p = 0.02). All effect sizes were moderate to large. In conclusion, after a mHealth exercise intervention, we demonstrated changes with large effect sizes in several CpG sites in the TNFα promoter region. Exercise levels were correlated with increases in TNFα promoter methylation. Larger exercise trials are needed to better evaluate TNFα regulation to inform interventions to augment TNFα regulation in order to improve outcomes in older adults with cancer.