FIGURE 4.

Canonical and extra‐telomeric functions of telomerase and the exercise‐mediated regulation in healthy ageing. A single bout and long‐term exercise training increases the expression of TERT and telomerase activity presumably to attenuate telomere attrition through its canonical function. Although long‐term resistance training appears to increase TERT expression in leukocytes, neither a single bout nor long‐term training modulates telomerase activity in human PBMCs. As part of its extra‐telomeric functions, TERT acts as a chromatin remodeller (through interactions with BRG1, as well as increasing DNMT3B expression) and influences transcriptional profiles. TERT protects against DNA damage, cell death, and safeguards the telomeres through the formation of a complex comprised of heat shock protein 70 and Apollo (Perera et al., 2019). In the presence of high reactive oxygen species (ROS), TERT is shuttled from the nucleus into the mitochondria where it prevents oxidative stress and mitochondrial DNA damage (mtDNA), enhances oxidative function, membrane potential, and transcribes RNA from the mitochondrial genome, suggesting it may promote mitochondrial biogenesis. Positive feedback loops exist between TERT and PGC1α, as well as TERT and β‐catenin/Wnt signalling. The former links TERT to metabolism and mitochondrial function, whereas the latter suggests involvement in stem cell homeostasis. Supported by Servier Medical Art. Solid lines = evidence for exercise regulation; dotted lines = evidence indicating a positive effect of TERT in other models; ? = denotes a potential role in the healthy biological ageing conferred by exercise training; red line = acute exercise effect; blue line = chronic exercise effect.