Even at 100+: Acute Exercise Modulates Inflammatory Pathways in Centenarians

Abstract

Centenarians exhibit remarkable disease resilience despite chronic low-grade inflammation. We investigated the inflammation-related proteome response to acute exercise in seven centenarians (100-104 years). Exercise downregulated 52 proteins (e.g., TNF, IL10, IL1RN, CCL family members) involved in immune cell trafficking, apoptosis, and cytokine regulation. Even at the extreme end of the lifespan, humans retain molecular responsiveness to exercise, with modulation of inflammation-related pathways.

FIGURE 1

Study design and inflammation‐related proteome after acute exercise. (A) Study design. Volcano plots indicating the differentially expressed proteins after an acute bout of exercise (blood sample 1 vs. blood sample 2) (B) or a resting (control) session (blood sample 3 vs. blood sample 4) (C). Proteins with significant upregulation or downregulation are color‐coded based on thresholds for statistical significance: p < 0.05 (blue) and p < 0.01 (yellow). (D) Venn diagram displaying overlapping and differentially expressed proteins in the exercise and control sessions.

FIGURE 2

Enrichment and network analyses of inflammation‐related proteins modulated by acute exercise. (A) Heatmap of selected enriched aging‐related pathways altered by exercise. (B) Protein–protein interaction network analysis showing the 16 highly connected inflammatory proteins that were downregulated by exercise. Symbol: *indicates those proteins associated with enriched pathways (Panel A, x‐axis).