DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy

Lin, Qiong; Weidner, Carola I.; Costa, Ivan G.; Marioni, Riccardo E.; Ferreira, Marcelo U.; Deary, Ian J.; Wagner, Wolfgang

doi:10.18632/aging.100908

Cited by 130 publications

(129 citation statements)

References 26 publications

(54 reference statements)

Supporting

Mentioning

126

Contrasting

Order By: Relevance

“…To date, multiple epigenetic predictors of age have been proposed in order to estimate the correct chronological, as well as biological, age of the organism, but these have only applied to a single source of DNA, such as saliva or blood [20,[33][34][35]. According to the epigenetic clock, both embryonic and induced-pluripotent stem cells display a DNA methylation age close to zero [19], consistent with the erasure of lineagespecific DNA methylation marks observed during the reprogramming process [36].…”

Section: The Epigenetic Clockmentioning

confidence: 99%

Interindividual epigenetic variability: Sound or noise?

Tejedor

Fraga

2017

BioEssays

View full text Add to dashboard Buy / Rent full text

Interindividual variability is an inherent characteristic of biological systems. Whereas the underlying molecular sources of interindividual variability remain poorly understood, recent work by Ecker et al. (Ecker S, Chen L, Pancaldi V, Bagger FO, et al. 2017. Genome Biol 18: 18.) sheds light on the characterization of this phenomenon in a complex biological scenario. By combining data from the BLUEPRINT Epigenome Project with a novel analytical approach, these authors were able to measure the degree of transcriptional and epigenetic variability across a wide panel of samples and types of immune cell. Interestingly, neutrophils displayed increased variability compared to monocytes and T cells, which may be related to the crucial role of the former as an initial mediator of immune responses. Here we review recent literature in this area, and discuss some important issues raised by these innovative analyses. Furthermore, we summarize other potential sources of epigenetic variability, such as epigenetic drift and the epigenetic clock, as well as the current ongoing direction of the field. Differential molecular variability of immune cell typesA recent report by Ecker and co-workers has unraveled, in a genome-wide manner, the extent of transcriptional and epigenetic variability in three major immune cell types [11]. Taking advantage of the publicly available BLUEPRINT Human Variation Panel, the authors analyzed RNA-seq and array-based DNA methylation data from 125 donors using transcriptomic and epigenomic datasets matched across

show abstract

Section: The Epigenetic Clockmentioning

confidence: 99%

Interindividual epigenetic variability: Sound or noise?

Tejedor

Fraga

2017

BioEssays

View full text Add to dashboard Buy / Rent full text

show abstract

“…DNA methylation and gene expression have been used to develop molecular markers or signatures associated with chronological age (Bocklandt et al., 2011; Hannum et al., 2013; Horvath, 2013; Lin et al., 2016; Weidner et al., 2014). The “epigenetic clock,” a biomarker index that combines weighted information of a subset of DNA methylation sites raised great interest because it is both strongly associated with chronological age across multiple tissues and populations and independent of age, predicts multiple health outcomes, including cardiovascular disease, cancer, and mortality (Chen et al., 2016; Levine et al., 2015; Perna et al., 2016).…”

Section: Introductionmentioning

confidence: 99%

Plasma proteomic signature of age in healthy humans

Tanaka¹,

Biancotto²,

Moaddel³

et al. 2018

Aging Cell

254

276

View full text Add to dashboard Buy / Rent full text

To characterize the proteomic signature of chronological age, 1,301 proteins were measured in plasma using the SOMAscan assay (SomaLogic, Boulder, CO, USA) in a population of 240 healthy men and women, 22–93 years old, who were disease‐ and treatment‐free and had no physical and cognitive impairment. Using a p ≤ 3.83 × 10−5 significance threshold, 197 proteins were positively associated, and 20 proteins were negatively associated with age. Growth differentiation factor 15 (GDF15) had the strongest, positive association with age (GDF15; 0.018 ± 0.001, p = 7.49 × 10−56). In our sample, GDF15 was not associated with other cardiovascular risk factors such as cholesterol or inflammatory markers. The functional pathways enriched in the 217 age‐associated proteins included blood coagulation, chemokine and inflammatory pathways, axon guidance, peptidase activity, and apoptosis. Using elastic net regression models, we created a proteomic signature of age based on relative concentrations of 76 proteins that highly correlated with chronological age (r = 0.94). The generalizability of our findings needs replication in an independent cohort.

show abstract

“…However, regulation of the epigenetic landscape can turn specific genes on and off in a reversible manner [17,18]. Particularly DNA methylation patterns are suggested to change in an age dependent manner including local hypermethylation and global hypomethylation [19][20][21]. Latter notably emerges at repetitive DNA sequences and thus is believed to be responsible for reactivating retro transposon elements during age resulting in a higher incidence of cancer [22,23].…”

Section: Introductionmentioning

confidence: 99%

“…This decrease in DNA methylation can be measured by the DNA methylation of the repetitive element LINE-1 which is spread throughout the genome [24]. Apart from global methylation patterns local DNA methylation of very specific DNA sites can also be correlated with the age of individuals [19,21,25]. Weidner et al could identify a set of three age-related CpGs-located in the genes ITGA2B, ASPA and PDE4C-which correlated very precisely with a variety of physiological parameters of biological aging [25].…”

Section: Introductionmentioning

confidence: 99%

EGCG Containing Combined Dietary Supplement Affects Telomeres and Epigenetic Regulation

Pointner¹,

Magnet²,

Tomeva³

et al. 2017

J Nutr Food Sci

View full text Add to dashboard Buy / Rent full text

Objective: In vitro and in vivo studies in rodents have demonstrated many health promoting properties of individual phytochemicals including antioxidative and chemopreventive effects. Recently combination of substances is claimed to enhance activity.The objective of this study was to investigate health benefits of a daily consumption of a combination of a large variety of phytochemicals (TimeBlock ® ). To assess potential changes we analyzed specific biomarkers that are associated with aging, oxidative stress and DNA stability: Methylation of LINE-1, c-Myc, IL-6, MLH1, DNMT1, ITGA2B and telomere length. Methods:For this study 110 healthy participants of both sexes between 31-76 years were recruited, 101 subjects were included in further analysis. A small reference group (n=20) without intervention within the same age interval served as control. Participants received a plant based dietary supplement (TimeBlock ® ) for 6 months by oral administration. Ingredients included extracts from green tea (EGCG), wheatgrass (tocotrienols), barley grass (folic acid), tomatoes (lycopene), tagetes (zeaxanthin, lutein), algae, shiitake mushrooms (vitamin D) and grape seeds (resveratrol). Capillary blood samples were collected from all participants before administration and within 6 days after the end of the study period following DNA extraction, bisulfite conversion and qPCR as well as high resolution melting curve analysis addressing analysis of LINE-1, c-Myc, IL-6, MLH1, DNMT1, ITGA2B and telomere length. Nutrition, lifestyle and health status were assessed with a standardized food and lifestyle questionnaire. Results and discussion:Our results confirmed the positive effect of plant derived antioxidants on telomeres and inflammation frequency. An age-specific drift of analyzed markers could be observed. While methylation of c-Myc-a key factor in telomerase regulation-was not affected by administration, total telomere length showed a significant increase, which we suggest to be linked with an increased cell turnover and accelerated apoptosis of senescent or mutated cells without enhancing telomerase activity. Further, methylation of mismatch repair protein gene MLH1 showed a strong negative correlation with telomere length, supporting the influence of MMR on telomere regulation. Conclusion:The results of the present study indicate that a combined administration of a variety of phytochemicals can be a potential preventive and therapeutic agent, as each substance exhibits different modes of action and in combination, health promoting effects could be potentiated. Addressing different mechanisms of aging, specific phytochemicals could be used as new therapeutic approach against age-related diseases.

show abstract

DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy

Cited by 130 publications

References 26 publications

Interindividual epigenetic variability: Sound or noise?

Interindividual epigenetic variability: Sound or noise?

Plasma proteomic signature of age in healthy humans

EGCG Containing Combined Dietary Supplement Affects Telomeres and Epigenetic Regulation

Contact Info

Product

Resources

About