Circulating cell-free DNA, telomere length and bilirubin in the Vienna Active Ageing Study: exploratory analysis of a randomized, controlled trial

Abstract

Telomere length (TL) in blood cells is widely used in human studies as a molecular marker of ageing. Circulating cell-free DNA (cfDNA) as well as unconjugated bilirubin (UCB) are dynamic blood constituents whose involvement in age-associated diseases is largely unexplored. To our knowledge, there are no published studies integrating all three parameters, especially in individuals of advanced age. Here we present a secondary analysis from the Vienna Active Aging Study (VAAS), a randomized controlled intervention trial in institutionalized elderly individuals (n = 101). Using an exploratory approach we combine three blood-based molecular markers (TL, UCB and cfDNA) with a range of primary and secondary outcomes from the intervention. We further look at the changes occurring in these parameters after 6-month resistance exercise training with or without supplementation. A correlation between UCB and TL was evident at baseline (p < 0.05), and both were associated with increased chromosomal anomalies such as nucleoplasmatic bridges and nuclear buds (p < 0.05). Of the three main markers explored in this paper, only cfDNA decreased significantly (p < 0.05) after 6-month training and dietary intervention. No clear relationship could be established between cfDNA and either UCB or TL. The trial was registered at ClinicalTrials.gov (NCT01775111).

Resistance Training Diminishes the Expression of Exosome CD63 Protein without Modification of Plasma miR-146a-5p and cfDNA in the Elderly

“…However, Jylhävä and colleagues recruited nonagenarians, aged from 90 to 99 years old, while our elderly participants were ~70 years old. In agreement with our results, Tosevska et al [ 35 ] showed no change in plasma cfDNA levels in older adults following a 6-month resistance training, although the literature has recently demonstrated that both acute aerobics and resistance exercise elicit an elevation in the circulating cfDNA as a potential biomarker for obesity-associated inflammatory responses [ 49 ] and also muscle damage-related performance decrement [ 50 ], respectively. Since skeletal muscle is the primary source of cfDNA release to exercise, future research should investigate the effects of training modalities and intensities/durations to optimize the health benefits of physiological adaptation attributable to age-related muscle loss.…”

“…Additionally, several studies have investigated the effects of exercise on the release of age-related biomarkers, such as cfDNA, or inflammaging-related mitochondrial miRNAs, such as miR-146a-5p. For instance, the plasma level of cfDNA was decreased in older adults following a combination of 6-month resistance training and nutritional supplementation (protein and micronutrients [e.g., vitamins C and E]) [ 35 ]. Furthermore, Morais Junior et al [ 36 ] examined acute effect of 1-week resistance exercise protocol in elderly subjects and found an increase in the circulating level of miR-146a-5p.…”

The effect of a 12-week resistance training intervention on leukocyte telomere length

“…In support of the possible association between resistance training and TL, 12 weeks of low frequency, moderate intensity, explosive-type resistance training prevented telomere shortening (Dimauro et al, 2016). However, TL was unchanged in both sedentary and elderly individuals following separate 6-month resistance training interventions (Tosevska et al, 2016;Werner et al, 2018).…”

Serum anti-inflammatory and inflammatory markers have no causal impact on telomere length: a Mendelian randomization study

“…This beneficial effect might be attributed to the radical scavenging activity of bilirubin, which in turn may delay telomere shortening by maintaining a balanced redox. Two other studies found a positive association between unconjugated bilirubin and TL [53,54] whereas a significant relationship between total and indirect bilirubin with TL was not found [55,56]. SUA may also represent a risk factor for cardiovascular disease [57,58].…”