Background: The aim of this prospective, randomized and controlled training study was to assess the molecular effects of physical training in circulating mononuclear cells and to test whether different training modalities exert differential effects on molecular regulators of cellular aging.

Methods: n=69 healthy non-smokers without regular physical activity aged 30–60 years were enrolled and randomized to a control group (control; no change of inactive life-style) or to one of three training interventions: 1) aerobic endurance training (AET, continuous running); 2) high-intensive interval training (IT, 4x4 method) or 3) strength endurance training (SET; circle training on 8 devices). Physical performance capacity was determined by cardiopulmonary exercise testing (CPET) on the treadmill at baseline and after the training period. The intervention consisted of 3 training sessions per week (45 min each) for a total duration of 6 months. Isolation of peripheral blood mononuclear cells (MNC) and molecular analyses were performed before the first and after the last training session.

Results: Telomerase activity and mRNA expression (real-time PCR) of telomere repeat-binding factor 2 (TRF2) and senescence marker p16 were measured. The training induced an increase of both, submaximal fitness parameters such as running speed on the treadmill at a pulse of 150/min (control: 0.23±0.1; AET: 0.74±0.2; IT: 1.05±0.1; SET: 0.18±0.1 km/h), and peak oxygen uptake (control: −0.21±0.6; AET: 4.74±0.8; IT: 4.22±1.1; SET: 2.44±1.2 ml/kg*min), which was higher in endurance compared to strength training. Quantification of telomerase activity (TRAP assay, compared to HEK cells as positive controls) in MNC revealed a significant 4–5-fold increase in both endurance exercise groups, but not in strength training (Δ pre/post: control 45±46; AET 287±150; IT 225±85; SET −15±52 HEK cell equivalents). Expression of the telomere capping factor TRF2 was increased compared to baseline levels (pre vs. post: control 119±17; AET 272±73; IT 444±134; SET 348±132%) and senescence marker p16 was decreased (pre vs. post: control 104±17; AET 65±17; IT 77±15; SET 54±15%) in all three trainings groups.

Conclusion: The study is the first prospective randomized, controlled trial showing that physical exercise mediates effects on telomere-regulating proteins and senescence markers in circulating cells. Cellular mediators of “anti-aging” were increased in all three training groups, however the activity of the enzyme telomerase was increased in endurance and in high-intensive interval training but not after strength training.