Telomeres and Physical Activity: What 16 RCTs Say

What are telomeres and why do they matter for aging?

Telomeres are the end segments of chromosomes, composed of repeating nucleotide sequences (TTAGGG in humans). They function as protective "caps" that prevent chromosomal degradation and fusion. With each cell division, telomeres shorten because DNA polymerase cannot fully copy the ends of linear chromosomes — this is known as the "end replication problem."

When telomeres reach a critical length, the cell enters senescence (an irreversible halt in division) or undergoes apoptosis. The accumulation of senescent cells is associated with chronic inflammation, impaired tissue regeneration, and a number of age-related conditions. Accelerated telomere shortening is observed under chronic psychological stress, obesity, and a sedentary lifestyle — through mechanisms of oxidative stress and pro-inflammatory cytokines.

Telomerase is an enzyme capable of adding telomeric repeats to chromosome ends. Its activity is high in stem and immune cells, but declines in most somatic cells with age. Lifestyle factors, including physical activity, can modulate telomerase activity.

What did the meta-analysis of 16 RCTs (2025) show?

Sun et al. (Frontiers in Physiology, 2025) conducted a systematic review and meta-analysis of randomized controlled trials examining the effects of physical exercise on telomeric biomarkers of aging. Inclusion criteria: adult participants, measurement of telomere length or telomerase activity before and after intervention, presence of a control group.

Final sample: 16 RCTs, 1908 participants (1005 — intervention, 903 — control). Studies were conducted across diverse populations: healthy adults, older adults, and individuals with metabolic disorders.

Key findings:

• Telomere length: exercise significantly maintained telomere length — standardized mean difference (SMD) = 0.59 (p = 0.01) across 14 studies.
• Telomerase activity: exercise increased enzyme activity — SMD = 0.35 (p < 0.00001) across 9 studies.
• Minimum duration for a significant effect on telomere length: 16 weeks; short-term interventions showed inconsistent results.

Which type of exercise works best?

Sun et al. compared exercise types and found the following picture:

• Aerobic exercise — the most consistent and reproducible effect on telomerase activity: SMD = 0.33 (p = 0.0001). The mechanism is linked to reduced oxidative stress and chronic inflammation through activation of antioxidant enzymes and suppression of pro-inflammatory cytokines.
• HIIT (high-intensity interval training) — the single included study found a higher effect on telomere length (SMD = 0.66, p = 0.01), however the conclusions are based on one study and cannot be considered confirmed.
• Resistance training — non-significant effect: SMD = 0.16 (p = 0.43). This is consistent with data from previous reviews.

Earlier, in 2024, Sánchez-González et al. (JMIR Public Health and Surveillance) published an earlier meta-analysis on the same topic: 7 RCTs, 1320 participants (98% women). The overall effect of exercise on telomere length was non-significant (MD = 0.0058, p = 0.83), however a subgroup analysis of HIIT yielded a significant result (MD = 0.15, 95% CI 0.03–0.26, p = 0.01). The authors rated evidence quality as "very low — low" on the GRADE scale. The discrepancy with the Sun et al. meta-analysis is explained by differences in inclusion criteria and sample composition.

What mechanisms explain this effect?

Physical exercise affects telomeres through at least two interrelated pathways. The first is reduction of oxidative stress: regular exercise activates antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase), which reduces the number of free radicals that directly damage telomeric DNA. The second is the anti-inflammatory effect: moderate aerobic exercise chronically lowers levels of pro-inflammatory cytokines (IL-6, TNF-alpha), which also accelerate telomeric degradation through oxidative stress.

An additional mechanism is telomerase regulation. Acute aerobic exercise transiently increases expression of the catalytic subunit of telomerase (hTERT) in peripheral blood mononuclear cells. With chronic exposure, this effect accumulates and leads to a sustained increase in enzyme activity, as recorded in RCTs.