Differential effects of endurance, interval, and resistance training on telomerase activity and telomere length in a randomized, controlled study

Abstract

Aims: It is unknown whether different training modalities exert differential cellular effects. Telomeres and telomere-associated proteins play a major role in cellular aging with implications for global health. This prospective training study examines the effects of endurance training, interval training (IT), and resistance training (RT) on telomerase activity and telomere length (TL).

Methods and results: One hundred and twenty-four healthy previously inactive individuals completed the 6 months study. Participants were randomized to three different interventions or the control condition (no change in lifestyle): aerobic endurance training (AET, continuous running), high-intensive IT (4 × 4 method), or RT (circle training on 8 devices), each intervention consisting of three 45 min training sessions per week. Maximum oxygen uptake (VO2max) was increased by all three training modalities. Telomerase activity in blood mononuclear cells was up-regulated by two- to three-fold in both endurance exercise groups (AET, IT), but not with RT. In parallel, lymphocyte, granulocyte, and leucocyte TL increased in the endurance-trained groups but not in the RT group. Magnet-activated cell sorting with telomerase repeat-ampliflication protocol (MACS-TRAP) assays revealed that a single bout of endurance training-but not RT-acutely increased telomerase activity in CD14+ and in CD34+ leucocytes.

Conclusion: This randomized controlled trial shows that endurance training, IT, and RT protocols induce specific cellular pathways in circulating leucocytes. Endurance training and IT, but not RT, increased telomerase activity and TL which are important for cellular senescence, regenerative capacity, and thus, healthy aging.

Figure 1

Acute effects of aerobic endurance vs. resistance exercise on telomerase activity. (A) Cross-over comparison of acute regulation of mononuclear cell telomerase activity pre, post, and 24 h after aerobic endurance training (45 min continuous running) and resistance exercise (45 min circle training on eight strength devices) in n = 15 healthy young individuals. Exercise was performed at least 48 h after any previous physical exercise. Telomerase activity of 10⁴ mononuclear cell was compared with human embryonic kidney cells (telomere repeat amplification protocols, TRAP assay). Time course of individual % changes of telomerase activity in 10⁴ magnetic-activated cell sorting-isolated (B) CD14+ and (C) CD34+ leucocyte subfractions compared with pre-exercise in n = 10 healthy young individuals (blue circles: endurance exercise; green circles: resistance exercise).

Figure 2

Design of the prospective, randomized, and controlled 6 months training study. Individuals enrolled in the study were randomized to the control group (no change of inactive life style) or one of three training groups (three sessions per week, 45 min each): (i) aerobic endurance training (continuous running); (ii) high-intensity interval training (4 × 4 method); (iii) resistance training: circle training on eight strength–endurance training devices. Blood samples were drawn at baseline (pre) and after 6 months (post). *Discontinuation for orthopaedic reasons was not training-associated. ^#Plausible stress test was defined as a respiratory exchange ratio of >1.00 in both stress tests.

Figure 3

Endurance but not resistance training induces telomere elongation in lymphocytes and granulocytes. Telomere length was measured in mononuclear cells using the FlowFISH method. Absolute values of telomere length (kbp) were calculated using Southern blot standardization. Individual absolute values of (A) lymphocyte and (B) granulocyte telomere length pre- and post-study time points for each group and means of each group are shown as bold blue bars. AET, aerobic endurance training; IT, interval training; RT, resistance training. (C) FlowFISH FACS blots showing telomere fluorescence intensity peaks for a representative subject of each study group (columns) and pre- vs. post-time points (upper and lower row, respectively). Red peaks are the internal standard (bovine thymocytes) in each sample, blue peaks are lymphocytes, and green peaks are granulocyte measurements. Dotted lines are for visualization of rightward or leftward shifts in the peaks during the study. (D) Mean and SD of relative individual changes of lymphocyte (left panel) and (E) granulocyte (right panel) telomere length for each group.

Figure 4

Differential effects of training on telomerase activity and telomere length in circulating mononuclear cells. (A) Leucocyte telomere length was determined in genomic DNA isolates by real-time PCR. Beside telomere (T) DNA, the single (S) copy gene 36b4 was amplified to allow calculation of T/S ratio for each subject at both time points. Data are represented as mean ± SD of T/S ratio per group. (B) Telomerase activity was determined by TRAP assay. Data are represented as mean ± SD of telomerase activity expressed as human embryonic kidney cell equivalents.

Figure 5

Cortisol production in acute extreme exercise vs. chronic exercise and training response. (A) Serum concentrations of the stress hormone cortisol were measured in N = 10 male samples of the Berlin Beat of Running marathon study and compared with (B) cortisol concentrations in 40 samples (10 per experimental group) of the chronic exercise study. (C) mRNA expression of the inducible nitric oxide synthase (real-time PCR). (D) Training response is associated with markers of cellular senescence: responders in the training groups with respect to the change of maximum oxygen uptake (ΔVO_2max) after the study compared with baseline were defined as the individuals above the mean of ΔVO_2max as opposed to ‘weak’ responders with a ΔVO_2max below the mean. Comparison of the change in telomerase activity shown as Δ human embryonic kidney cell equivalents between subjects below vs. above the mean of the ΔVO_2max.

Take home figure

In a primary prevention cohort of untrained healthy middle-aged subjects, aerobic endurance training, or intensive interval training for 6 months increased telomerase activity and telomere length, indicating vascular anti-aging effects. No changes were observed in the control and resistance training groups.