scholarly journals Predicting cellular aging following exposure to adversity: Does accumulation, recency, or developmental timing of exposure matter?

2018 ◽  
Author(s):  
Sandro Marini ◽  
Kathryn A. Davis ◽  
Thomas W. Soare ◽  
Matthew J. Suderman ◽  
Andrew J. Simpkin ◽  
...  
Keyword(s):  
Middle Childhood ◽  
Repeated Measures ◽  
Selection Procedure ◽  
Cellular Aging ◽  
Sensitive Period ◽  
Developmental Timing ◽  
Biological Aging ◽  
Sensitive Periods ◽  
Epigenetic Aging ◽  
Epigenetic Age

AbstractExposure to adversity has been linked to accelerated biological aging, which in turn has been shown to predict numerous health problems, including neuropsychiatric disease. In recent years, measures of DNA methylation-based epigenetic age – known as “epigenetic clocks” – have been used to estimate accelerated epigenetic aging. Yet, few studies have been conducted in children. Using data from the Avon Longitudinal Study of Parents and Children (n=973), we explored the prospective association between repeated measures of childhood exposure to seven types of adversity on epigenetic age assessed at age 7 using the Horvath and Hannum epigenetic clocks. With a Least Angle Regression variable selection procedure, we evaluated the effects of the developmental timing, accumulation, and recency of adversity exposure. We found that exposure to sexual or physical abuse, financial stress, or neighborhood disadvantage during sensitive periods in early and middle childhood best explained variability in the deviation of the Hannum epigenetic age from the chronological age. Secondary sex-stratified analyses identified particularly strong sensitive period effects, such that by age 7, girls who were exposed to abuse at age 3.5 were biologically older than their unexposed peers by almost 2 months. These effects were undetected in analyses comparing children “exposed” versus “unexposed” to adversity. Our results suggest that exposure to adversity may alter methylation processes in ways that perturb normal cellular aging and that these effects may be heightened during sensitive periods in development. Research is needed to demonstrate the effect of accelerated epigenetic aging on negative health outcomes following childhood adversity exposure.

scholarly journals The costs of competition: high social status males experience accelerated epigenetic aging in wild baboons

2020 ◽  
Author(s):  
Jordan A. Anderson ◽  
Rachel A. Johnston ◽  
Amanda J. Lea ◽  
Fernando A. Campos ◽  
Tawni N. Voyles ◽  
...  
Keyword(s):  
Dominance Rank ◽  
Natural Populations ◽  
Life History Strategy ◽  
Male Dominance ◽  
Biological Aging ◽  
Epigenetic Clock ◽  
Epigenetic Aging ◽  
Epigenetic Age ◽  
Aging Rates ◽  
Young Life

AbstractAging, for virtually all life, is inescapable. However, within populations, biological aging rates vary. Understanding sources of variation in this process is central to understanding the biodemography of natural populations. We constructed a DNA methylation-based age predictor for an intensively studied wild baboon population in Kenya. Consistent with findings in humans, the resulting “epigenetic clock” closely tracks chronological age, but individuals are predicted to be somewhat older or younger than their known ages. Surprisingly, these deviations are not explained by the strongest predictors of lifespan in this population, early adversity and social integration. Instead, they are best predicted by male dominance rank: high-ranking males are predicted to be older than their true ages, and epigenetic age tracks changes in rank over time. Our results argue that achieving high rank for male baboons—the best predictor of reproductive success—imposes costs consistent with a “live fast, die young” life history strategy.

scholarly journals An epigenetic aging analysis of randomized metformin and weight loss interventions in overweight postmenopausal breast cancer survivors

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jamaji C. Nwanaji-Enwerem ◽  
Felicia Fei-Lei Chung ◽  
Lars Van der Laan ◽  
Alexei Novoloaca ◽  
Cyrille Cuenin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Weight Loss ◽  
Cancer Survivors ◽  
Breast Cancer Survivors ◽  
Controlled Trial ◽  
Postmenopausal Breast Cancer ◽  
Biological Aging ◽  
Epigenetic Aging ◽  
Epigenetic Age ◽  
Registration Number

AbstractMetformin and weight loss relationships with epigenetic age measures—biological aging biomarkers—remain understudied. We performed a post-hoc analysis of a randomized controlled trial among overweight/obese breast cancer survivors (N = 192) assigned to metformin, placebo, weight loss with metformin, or weight loss with placebo interventions for 6 months. Epigenetic age was correlated with chronological age (r = 0.20–0.86; P < 0.005). However, no significant epigenetic aging associations were observed by intervention arms. Consistent with published reports in non-cancer patients, 6 months of metformin therapy may be inadequate to observe expected epigenetic age deceleration. Longer duration studies are needed to better characterize these relationships.Trial Registration: Registry Name: ClincialTrials.Gov.Registration Number: NCT01302379.Date of Registration: February 2011.URL:https://clinicaltrials.gov/ct2/show/NCT01302379

scholarly journals Deconvolution of the epigenetic age discloses distinct inter-personal variability in epigenetic aging patterns

2021 ◽  
Author(s):  
Tamar Shahal ◽  
Elad Segev ◽  
Thomas Konstantinovsky ◽  
Yonit Marcus ◽  
Gabi Shefer ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Interindividual Variability ◽  
Chronological Age ◽  
Biological Aging ◽  
Epigenetic Clock ◽  
Cpg Sites ◽  
Epigenetic Aging ◽  
Epigenetic Age ◽  
Shed Light

Epigenetic age not only correlates with chronological age but predicts morbidity and mortality. We assumed that deconvolution of epigenetic age to its individual components could shed light on the diversity of epigenetic, and by inference, biological aging. Using the Horvath original epigenetic clock, we identified several CpG sites linked to distinct genes that quantitatively explain much of the interpersonal variability in epigenetic aging, with secretagogin and malin showing the most dominant effects. The analysis shows that the same epigenetic age for any given chronological age can be accounted for by variable contributions of identifiable CpG sites; that old epigenetic relative to chronological age is mostly explained by the same CpG sites, mapped to genes showing the highest interindividual variability differences in healthy subjects but not in subjects with type 2 diabetes. This paves the way to form personalized aging cards indicating the sources of accelerated/decelerated epigenetic aging in each examinee, en route to targeting specific sites as indicators, and perhaps treatment targets of personal undesirable age drifting.

scholarly journals Targeted methods for epigenetic age predictions in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yang Han ◽  
Miloš Nikolić ◽  
Michael Gobs ◽  
Julia Franzen ◽  
Gerald de Haan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Model Organism ◽  
Amplicon Sequencing ◽  
Digital Pcr ◽  
Biological Aging ◽  
Epigenetic Aging ◽  
Epigenetic Age ◽  
Trait Locus ◽  
Genomic Regions ◽  
Cg Dinucleotides

AbstractAge-associated DNA methylation reflects aspect of biological aging—therefore epigenetic clocks for mice can elucidate how the aging process in this model organism is affected by specific treatments or genetic background. Initially, age-predictors for mice were trained for genome-wide DNA methylation profiles and we have recently described a targeted assay based on pyrosequencing of DNA methylation at only three age-associated genomic regions. Here, we established alternative approaches using droplet digital PCR (ddPCR) and barcoded bisulfite amplicon sequencing (BBA-seq). At individual CG dinucleotides (CpGs) the correlation of DNA methylation with chronological age was slightly higher for pyrosequencing and ddPCR as compared to BBA-seq. On the other hand, BBA-seq revealed that neighboring CpGs tend to be stochastically modified at murine age-associated regions. Furthermore, the binary sequel of methylated and non-methylated CpGs in individual reads can be used for single-read predictions, which may reflect heterogeneity in epigenetic aging. In comparison to C57BL/6 mice the single-read age-predictions using BBA-seq were also accelerated in the shorter-lived DBA/2 mice, and in C57BL/6 mice with a lifespan quantitative trait locus of DBA/2 mice. Taken together, we describe alternative targeted methods for epigenetic age predictions that provide new perspectives for aging-intervention studies in mice.

scholarly journals Does the epigenetic clock GrimAge predict mortality independent of genetic influences: an 18 year follow-up study in older female twin pairs

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Föhr Tiina ◽  
Waller Katja ◽  
Viljanen Anne ◽  
Sanchez Riikka ◽  
Ollikainen Miina ◽  
...  
Keyword(s):  
Mortality Risk ◽  
Genetic Factors ◽  
Strong Predictor ◽  
Genetic Influences ◽  
Biological Aging ◽  
Epigenetic Clock ◽  
Twin Design ◽  
Epigenetic Aging ◽  
Epigenetic Age

Abstract Background Epigenetic clocks are based on DNA methylation (DNAm). It has been suggested that these clocks are useable markers of biological aging and premature mortality. Because genetic factors explain variations in both epigenetic aging and mortality, this association could also be explained by shared genetic factors. We investigated the influence of genetic and lifestyle factors (smoking, alcohol consumption, physical activity, chronic diseases, body mass index) and education on the association of accelerated epigenetic aging with mortality using a longitudinal twin design. Utilizing a publicly available online tool, we calculated the epigenetic age using two epigenetic clocks, Horvath DNAmAge and DNAm GrimAge, in 413 Finnish twin sisters, aged 63–76 years, at the beginning of the 18-year mortality follow-up. Epigenetic age acceleration was calculated as the residuals from a linear regression model of epigenetic age estimated on chronological age (AAHorvath, AAGrimAge, respectively). Cox proportional hazard models were conducted for individuals and twin pairs. Results The results of the individual-based analyses showed an increased mortality hazard ratio (HR) of 1.31 (CI95: 1.13–1.53) per one standard deviation (SD) increase in AAGrimAge. The results indicated no significant associations of AAHorvath with mortality. Pairwise mortality analyses showed an HR of 1.50 (CI95: 1.02–2.20) per 1 SD increase in AAGrimAge. However, after adjusting for smoking, the HR attenuated substantially and was statistically non-significant (1.29; CI95: 0.84–1.99). Similarly, in multivariable adjusted models the HR (1.42–1.49) was non-significant. In AAHorvath, the non-significant HRs were lower among monozygotic pairs in comparison to dizygotic pairs, while in AAGrimAge there were no systematic differences by zygosity. Further, the pairwise analysis in quartiles showed that the increased within pair difference in AAGrimAge was associated with a higher all-cause mortality risk. Conclusions In conclusion, the findings suggest that DNAm GrimAge is a strong predictor of mortality independent of genetic influences. Smoking, which is known to alter DNAm levels and is built into the DNAm GrimAge algorithm, attenuated the association between epigenetic aging and mortality risk.

scholarly journals Epigenetic Aging and Colorectal Cancer: State of the Art and Perspectives for Future Research

2020 ◽  
Vol 22 (1) ◽  
pp. 200
Author(s):  
Andrea Maugeri ◽  
Martina Barchitta ◽  
Roberta Magnano San Lio ◽  
Giovanni Li Destri ◽  
Antonella Agodi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
State Of The Art ◽  
Biological Aging ◽  
Future Research ◽  
Molecular Response ◽  
Epigenetic Aging ◽  
Epigenetic Age ◽  
The Difference ◽  
Novel Concept ◽  
Risk Of Cancer

Although translational research has identified a large number of potential biomarkers involved in colorectal cancer (CRC) carcinogenesis, a better understanding of the molecular pathways associated with biological aging in colorectal cells and tissues is needed. Here, we aim to summarize the state of the art about the role of age acceleration, defined as the difference between epigenetic age and chronological age, in the development and progression of CRC. Some studies have shown that accelerated biological aging is positively associated with the risk of cancer and death in general. In line with these findings, other studies have shown how the assessment of epigenetic age in people at risk for CRC could be helpful for monitoring the molecular response to preventive interventions. Moreover, it would be interesting to investigate whether aberrant epigenetic aging could help identify CRC patients with a high risk of recurrence and a worst prognosis, as well as those who respond poorly to treatment. Yet, the application of this novel concept is still in its infancy, and further research should be encouraged in anticipation of future applications in clinical practice.

scholarly journals Epigenetic age-predictions in mice using pyrosequencing, droplet digital PCR or barcoded bisulfite amplicon sequencing

2020 ◽  
Author(s):  
Yang Han ◽  
Miloš Nikolić ◽  
Michael Gobs ◽  
Julia Franzen ◽  
Gerald de Haan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Model Organism ◽  
Amplicon Sequencing ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Biological Aging ◽  
Epigenetic Aging ◽  
Epigenetic Age ◽  
Trait Locus ◽  
The Impact

AbstractAge-associated DNA methylation reflects aspects of biological aging - therefore epigenetic clocks for mice can help to elucidate the impact of treatments or genetic background on the aging process in this model organism. Initially, age-predictors for mice were trained on genome-wide DNA methylation profiles, whereas we have recently described a targeted assay based on pyrosequencing of DNA methylation at only three CG dinucleotides (CpGs). Here, we have re-evaluated pyrosequencing approaches in comparison to droplet digital PCR (ddPCR) and barcoded bisulfite amplicon sequencing (BBA-seq). At individual CpGs the correlation of DNA methylation with chronological age was slightly higher for pyrosequencing and ddPCR as compared to BBA-seq. On the other hand, BBA-seq revealed that neighboring CpGs tend to be stochastically modified in murine age-associated regions. Furthermore, the binary sequel of methylated and non-methylated CpGs in individual reads can be used for single-read predictions, which may reflect heterogeneity in epigenetic aging. In comparison to C57BL/6 mice the epigenetic age-predictions using BBA-seq were also accelerated in the shorter-lived DBA/2 mice, and in C57BL/6 mice with a lifespan quantitative trait locus of DBA/2 mice. Taken together, we describe further optimized and alternative targeted methods to determine epigenetic clocks in mice.

scholarly journals Obesity and accelerated epigenetic aging in a high-risk cohort of children

2021 ◽  
Author(s):  
Laura Etzel ◽  
Waylon J. Hastings ◽  
Molly A. Hall ◽  
Christine Heim ◽  
Michael J. Meaney ◽  
...  
Keyword(s):  
High Risk ◽  
Continuous Variable ◽  
Cellular Aging ◽  
Health Study ◽  
Biological Aging ◽  
Blood Leukocytes ◽  
Cell Counts ◽  
Epigenetic Aging ◽  
The Impact ◽  
High Risk Cohort

Background: New insights into mechanisms linking obesity to poor health outcomes suggest a role for cellular aging pathways, casting obesity as a disease of accelerated biological aging. Although obesity has been linked to accelerated epigenetic aging in middle-aged adults, the impact during childhood remains unclear. We tested the association between body mass index (BMI) and accelerated epigenetic aging in a cohort of high-risk children. Participants were children (N=273, aged 8 to 14 years, 82% investigated for maltreatment) recruited to the Child Health Study, an ongoing prospective study of youth investigated for maltreatment and a comparison youth. BMI was measured as a continuous variable. Accelerated epigenetic aging of blood leukocytes was defined as the age-adjusted residuals of several established epigenetic aging clocks (Horvath, Hannum, GrimAge, PhenoAge) along with a newer algorithm, the DunedinPoAm, developed to quantify the pace-of-aging. Hypotheses were tested with generalized linear models. Results: Higher BMI was significantly correlated with older chronological age, maltreatment status, household income, blood cell counts, and three of the accelerated epigenetic aging measures: GrimAge (r=0.29, P<.0001), PhenoAge (r=0.25, P<.0001), and DunedinPoAm (r=0.37, P<.0001). In fully adjusted models, GrimAge (b=.06; P=.007) and DunedinPoAm (b=.0017; P<.0001) remained significantly associated with higher BMI. Maltreatment-status was not independently associated with accelerated epigenetic aging after accounting for other factors. Conclusion: In a high-risk cohort of children, higher BMI predicted epigenetic aging as assessed by two epigenetic aging clocks. These results suggest the association between obesity and accelerated epigenetic aging begins in early life, with implications for future morbidity and mortality risk.

scholarly journals Effects of Smoking Cessation on Epigenetic Aging

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 673-673
Author(s):  
Brian Chen ◽  
Weiye Wang ◽  
Nichole Rigby ◽  
Randal Olson ◽  
Steve Sabes
Keyword(s):  
Dna Methylation ◽  
Experimental Studies ◽  
Biological Aging ◽  
Multiple Time ◽  
Epigenetic Aging ◽  
Epigenetic Age ◽  
Epigenetic Age Acceleration ◽  
Aging Rates ◽  
Multiple Time Points ◽  
Over Time

Abstract “Epigenetic clocks” have become widely used to assess individual rates of biological aging. However, experimental data are limited in humans to identify potential confounding factors that may influence one’s rate of epigenetic aging and multiple health outcomes. We examined multiple epigenetic aging measures among regular smokers who quit smoking for two weeks. DNA methylation markers were assessed in both whole blood and saliva at multiple time points using a customized DNA methylation microarray. Generally, no changes in epigenetic aging rates were detected in the two week observation period with the exception of pronounced decreases over time in rate of Hannum’s clock and Extrinsic Epigenetic Age Acceleration in blood DNA. In saliva DNA, decreases over time were detected in the rates of the GrimAge and DNAmPhenoAge clocks, but we saw an increase in the rate of the Skin and Blood Clock. Additional experimental studies of other common exposures may be useful to better characterize factors that may affect the observed “rate” of epigenetic aging.

scholarly journals Cost-effective epigenetic age profiling in shallow methylation sequencing data

2021 ◽  
Author(s):  
Alexandre Trapp ◽  
Vadim N Gladyshev
Keyword(s):  
High Throughput ◽  
Aging Process ◽  
Large Scale ◽  
Cost Effective ◽  
Cellular Reprogramming ◽  
Biological Aging ◽  
Sequencing Data ◽  
Epigenetic Aging ◽  
Epigenetic Age ◽  
Fold Reduction

There is a critical need for robust, high-throughput assays of biological aging trajectories. Among various approaches, epigenetic aging clocks emerged as reliable molecular trackers of the aging process. However, current methods for epigenetic age profiling are inherently costly and lack throughput. Here, we leverage the scAge framework for accurate prediction of biological age from very few bisulfite sequencing reads in bulk samples, thereby enabling drastic (100-1,000-fold) reduction in sequencing costs per sample. Our approach permits age assessment based on distinct assortments of CpG sites in different samples, without the need for targeted site enrichment or specialized reagents. We demonstrate the efficacy of this method to quantify the age of mouse blood samples across independent cohorts, identify the effect of calorie restriction as an attenuator of the aging process, and discern rejuvenation upon cellular reprogramming. We propose that this framework may be used for epigenetic age prediction in extremely high-throughput applications, enabling robust, large-scale and inexpensive interventions testing and age profiling.

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