10
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Exploring Epigenetic Age in Response to Intensive Relaxing Training: A Pilot Study to Slow Down Biological Age

      research-article

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          DNA methylation (DNAm) is an emerging estimator of biological aging, i.e., the often-defined “epigenetic clock”, with a unique accuracy for chronological age estimation (DNAmAge). In this pilot longitudinal study, we examine the hypothesis that intensive relaxing training of 60 days in patients after myocardial infarction and in healthy subjects may influence leucocyte DNAmAge by turning back the epigenetic clock. Moreover, we compare DNAmAge with another mechanism of biological age, leucocyte telomere length (LTL) and telomerase. DNAmAge is reduced after training in healthy subjects ( p = 0.053), but not in patients. LTL is preserved after intervention in healthy subjects, while it continues to decrease in patients ( p = 0.051). The conventional negative correlation between LTL and chronological age becomes positive after training in both patients ( p < 0.01) and healthy subjects ( p < 0.05). In our subjects, DNAmAge is not associated with LTL. Our findings would suggest that intensive relaxing practices influence different aging molecular mechanisms, i.e., DNAmAge and LTL, with a rejuvenating effect. Our study reveals that DNAmAge may represent an accurate tool to measure the effectiveness of lifestyle-based interventions in the prevention of age-related diseases.

          Related collections

          Most cited references41

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          DNA methylation age of blood predicts all-cause mortality in later life

          Background DNA methylation levels change with age. Recent studies have identified biomarkers of chronological age based on DNA methylation levels. It is not yet known whether DNA methylation age captures aspects of biological age. Results Here we test whether differences between people’s chronological ages and estimated ages, DNA methylation age, predict all-cause mortality in later life. The difference between DNA methylation age and chronological age (Δage) was calculated in four longitudinal cohorts of older people. Meta-analysis of proportional hazards models from the four cohorts was used to determine the association between Δage and mortality. A 5-year higher Δage is associated with a 21% higher mortality risk, adjusting for age and sex. After further adjustments for childhood IQ, education, social class, hypertension, diabetes, cardiovascular disease, and APOE e4 status, there is a 16% increased mortality risk for those with a 5-year higher Δage. A pedigree-based heritability analysis of Δage was conducted in a separate cohort. The heritability of Δage was 0.43. Conclusions DNA methylation-derived measures of accelerated aging are heritable traits that predict mortality independently of health status, lifestyle factors, and known genetic factors. Electronic supplementary material The online version of this article (doi:10.1186/s13059-015-0584-6) contains supplementary material, which is available to authorized users.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions.

            Although the fact that genetic predisposition and environmental exposures interact to shape development and function of the human brain and, ultimately, the risk of psychiatric disorders has drawn wide interest, the corresponding molecular mechanisms have not yet been elucidated. We found that a functional polymorphism altering chromatin interaction between the transcription start site and long-range enhancers in the FK506 binding protein 5 (FKBP5) gene, an important regulator of the stress hormone system, increased the risk of developing stress-related psychiatric disorders in adulthood by allele-specific, childhood trauma-dependent DNA demethylation in functional glucocorticoid response elements of FKBP5. This demethylation was linked to increased stress-dependent gene transcription followed by a long-term dysregulation of the stress hormone system and a global effect on the function of immune cells and brain areas associated with stress regulation. This identification of molecular mechanisms of genotype-directed long-term environmental reactivity will be useful for designing more effective treatment strategies for stress-related disorders.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Aging of blood can be tracked by DNA methylation changes at just three CpG sites

              Background Human aging is associated with DNA methylation changes at specific sites in the genome. These epigenetic modifications may be used to track donor age for forensic analysis or to estimate biological age. Results We perform a comprehensive analysis of methylation profiles to narrow down 102 age-related CpG sites in blood. We demonstrate that most of these age-associated methylation changes are reversed in induced pluripotent stem cells (iPSCs). Methylation levels at three age-related CpGs - located in the genes ITGA2B, ASPA and PDE4C - were subsequently analyzed by bisulfite pyrosequencing of 151 blood samples. This epigenetic aging signature facilitates age predictions with a mean absolute deviation from chronological age of less than 5 years. This precision is higher than age predictions based on telomere length. Variation of age predictions correlates moderately with clinical and lifestyle parameters supporting the notion that age-associated methylation changes are associated more with biological age than with chronological age. Furthermore, patients with acquired aplastic anemia or dyskeratosis congenita - two diseases associated with progressive bone marrow failure and severe telomere attrition - are predicted to be prematurely aged. Conclusions Our epigenetic aging signature provides a simple biomarker to estimate the state of aging in blood. Age-associated DNA methylation changes are counteracted in iPSCs. On the other hand, over-estimation of chronological age in bone marrow failure syndromes is indicative for exhaustion of the hematopoietic cell pool. Thus, epigenetic changes upon aging seem to reflect biological aging of blood.
                Bookmark

                Author and article information

                Journal
                Int J Environ Res Public Health
                Int J Environ Res Public Health
                ijerph
                International Journal of Environmental Research and Public Health
                MDPI
                1661-7827
                1660-4601
                23 August 2019
                September 2019
                : 16
                : 17
                : 3074
                Affiliations
                [1 ]Occupational Medicine, Department of Cardiac, Thoracic, and Vascular Sciences and Public Health, University Hospital of Padua, Via Giustiniani, 2, 35128 Padova, Italy
                [2 ]Clinical Cardiology, Department of Cardiac, Thoracic, and Vascular Sciences and Public Health, University Hospital of Padua, Via Giustiniani, 2, 35128 Padova, Italy
                Author notes
                [* ]Correspondence: sofia.pavanello@ 123456unipd.it ; Tel.: +39-049-8216600
                Author information
                https://orcid.org/0000-0003-4828-7875
                Article
                ijerph-16-03074
                10.3390/ijerph16173074
                6747190
                31450859
                055e031a-b84e-484b-a6fa-b17290b295c0
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 12 July 2019
                : 20 August 2019
                Categories
                Article

                Public health
                epigenetic age,dna methylation age,relaxing training,telomere length,myocardial infarction patient,telomerase

                Comments

                Comment on this article