Epigenetic clock measuring age acceleration via DNA methylation levels in blood is associated with decreased oocyte yield

Monseur, Brent; Murugappan, Gayathree; Bentley, Jason; Teng, Nelson; Westphal, Lynn M.

doi:10.1007/s10815-020-01763-0

Cited by 17 publications

(16 citation statements)

References 27 publications

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“…Additionally, age acceleration (AgeAccel) ( Monseur et al, 2020 ) is defined as estimated age > 2 years older than chronologic age, which will avoid the number in the AgeAccel group thins quickly (e.g., 14 and 6 cases of AgeAccel if using > 5 and > 10, respectively). As a result, there were 21 SSVD patients with AgeAccel and 31 ones without AgeAccel in the present study.…”

Section: Resultsmentioning

confidence: 99%

Potential of brain age in identifying early cognitive impairment in subcortical small-vessel disease patients

Shi

Mao

Gao

et al. 2022

Front. Aging Neurosci.

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BackgroundReliable and individualized biomarkers are crucial for identifying early cognitive impairment in subcortical small-vessel disease (SSVD) patients. Personalized brain age prediction can effectively reflect cognitive impairment. Thus, the present study aimed to investigate the association of brain age with cognitive function in SSVD patients and assess the potential value of brain age in clinical assessment of SSVD.Materials and methodsA prediction model for brain age using the relevance vector regression algorithm was developed using 35 healthy controls. Subsequently, the prediction model was tested using 51 SSVD patients [24 subjective cognitive impairment (SCI) patients and 27 mild cognitive impairment (MCI) patients] to identify brain age-related imaging features. A support vector machine (SVM)-based classification model was constructed to differentiate MCI from SCI patients. The neurobiological basis of brain age-related imaging features was also investigated based on cognitive assessments and oxidative stress biomarkers.ResultsThe gray matter volume (GMV) imaging features accurately predicted brain age in individual patients with SSVD (R2 = 0.535, p < 0.001). The GMV features were primarily distributed across the subcortical system (e.g., thalamus) and dorsal attention network. SSVD patients with age acceleration showed significantly poorer Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA) scores. The classification model based on GMV features could accurately distinguish MCI patients from SCI patients (area under the curve = 0.883). The classification outputs of the classification model exhibited significant associations with MoCA scores, Trail Making Tests A and B scores, Stroop Color and Word Test C scores, information processing speed total scores, and plasma levels of total antioxidant capacity in SSVD patients.ConclusionBrain age can be accurately quantified using GMV imaging data and shows potential clinical value for identifying early cognitive impairment in SSVD patients.

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Section: Resultsmentioning

confidence: 99%

Potential of brain age in identifying early cognitive impairment in subcortical small-vessel disease patients

Shi

Mao

Gao

et al. 2022

Front. Aging Neurosci.

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“…The relationships between epigenetic biomarkers of aging and male or female infertility are understudied. Monseur et al (2020) reported an association between low oocyte yield and epigenetic age acceleration, and Hanson et al (2020) revealed an association between poor ovarian response to ovarian stimulation in ART and epigenetic age acceleration in white blood cells. However, these studies were underpowered due to their small sample size (Monseur et al , n = 39 and Hanson et al , n = 175), lacked an important control group (e.g.…”

Section: Introductionmentioning

confidence: 99%

Associations between epigenetic age acceleration and infertility

et al. 2022

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STUDY QUESTION Is the use of ART, a proxy for infertility, associated with epigenetic age acceleration? SUMMARY ANSWER The epigenetic age acceleration measured by Dunedin Pace of Aging methylation (DunedinPoAm) differed significantly between non-ART and ART mothers. WHAT IS KNOWN ALREADY Among mothers who used ART, epigenetic age acceleration may be associated with low oocyte yield and poor ovarian response. However, the difference in epigenetic age acceleration between non-ART and ART mothers (or even fathers) has not been examined. STUDY DESIGN, SIZE, DURATION The Norwegian Mother, Father and Child Cohort Study (MoBa) recruited pregnant women and their partners across Norway at around 18 gestational weeks between 1999 and 2008. Approximately 95 000 mothers, 75 000 fathers and 114 000 children were included. Peripheral blood samples were taken from mothers and fathers at ultrasound appointments or from mothers at childbirth, and umbilical cord blood samples were collected from the newborns at birth. PARTICIPANTS/MATERIALS, SETTING, METHODS Among the MoBa participants, we selected 1000 couples who conceived by coitus and 894 couples who conceived by IVF (n = 525) or ICSI (n = 369). We measured their DNA methylation (DNAm) levels using the Illumina MethylationEPIC array and calculated epigenetic age acceleration. A linear mixed model was used to examine the differences in five different epigenetic age accelerations between non-ART and ART parents. MAIN RESULTS AND THE ROLE OF CHANCE We found a significant difference in the epigenetic age acceleration calculated by DunedinPoAm between IVF and non-ART mothers (0.021 years, P-value = 2.89E−06) after adjustment for potential confounders. Further, we detected elevated DunedinPoAm in mothers with tubal factor infertility (0.030 years, P-value = 1.34E−05), ovulation factor (0.023 years, P-value = 0.0018) and unexplained infertility (0.023 years, P-value = 1.39E−04) compared with non-ART mothers. No differences in epigenetic age accelerations between non-ART and ICSI fathers were found. DunedinPoAm also showed stronger associations with smoking, education and parity than the other four epigenetic age accelerations. LIMITATIONS, REASONS FOR CAUTION We were not able to determine the directionality of the causal pathway between the epigenetic age accelerations and infertility. Since parents’ peripheral blood samples were collected after conception, we cannot rule out the possibility that the epigenetic profile of ART mothers was influenced by the ART treatment. Hence, the results should be interpreted with caution, and our results might not be generalizable to non-pregnant women. WIDER IMPLICATIONS OF THE FINDINGS A plausible biological mechanism behind the reported association is that IVF mothers could be closer to menopause than non-ART mothers. The pace of decline of the ovarian reserve that eventually leads to menopause varies between females yet, in general, accelerates after the age of 30, and some studies show an increased risk of infertility in females with low ovarian reserve. STUDY FUNDING/COMPETING INTEREST(S) This study was partly funded by the Research Council of Norway (Women’s fertility, project no. 320656) and through its Centres of Excellence Funding Scheme (project no. 262700). M.C.M. has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement number 947684). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

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“…Individual variation in epigenetic aging appears to be linked to numerous fundamental life history traits [ 12 ] including the precocious onset of puberty [ 23 ], menopause [ 24 ], and mortality [ 25 ]. Even more, epigenetic age appears to reflect aspects of reproductive effort, such as oocyte yield [ 26 ], number of pregnancies [ 27 ], and the birth weight of offspring [ 28 ]. Adverse environments are thought to affect plasticity in life history traits [ 1 ], and given that stressful [ 29 ] and polluted [ 30 ] environments are associated with epigenetic age-acceleration in humans, epigenetic aging presents a potential mechanism linking environmental factors and individual variation in biological aging.…”

Section: Introductionmentioning

confidence: 99%

Exposure to ionizing radiation disrupts normal epigenetic aging in Japanese medaka

Bertucci

Mason

Rhodes

et al. 2021

Aging

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Alterations to the epigenome are a hallmark of biological aging and age-dependent patterning of the DNA methylome (“epigenetic aging”) can be modeled to produce epigenetic age predictors. Rates of epigenetic aging vary amongst individuals and correlate to the onset of age-related disease and all-cause mortality. Yet, the origins of epigenetic-to-chronological age discordance are not empirically resolved. Here, we investigate the relationship between aging, DNA methylation, and environmental exposures in Japanese medaka ( Oryzias latipes ). We find age-associated DNA methylation patterning enriched in genomic regions of low CpG density and that, similar to mammals, most age-related changes occur during early life. We construct an epigenetic clock capable of predicting chronological age with a mean error of 61.1 days (~8.4% of average lifespan). To test the role of environmental factors in driving epigenetic age variation, we exposed medaka to chronic, environmentally relevant doses of ionizing radiation. Because most organisms share an evolutionary history with ionizing radiation, we hypothesized that exposure would reveal fundamental insights into environment-by-epigenetic aging interactions. Radiation exposure disrupted epigenetic aging by accelerating and decelerating normal age-associated patterning and was most pronounced in cytosines that were moderately associated with age. These findings empirically demonstrate the role of DNA methylation in integrating environmental factors into aging trajectories.

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Epigenetic clock measuring age acceleration via DNA methylation levels in blood is associated with decreased oocyte yield

Cited by 17 publications

References 27 publications

Potential of brain age in identifying early cognitive impairment in subcortical small-vessel disease patients

Potential of brain age in identifying early cognitive impairment in subcortical small-vessel disease patients

Associations between epigenetic age acceleration and infertility

Exposure to ionizing radiation disrupts normal epigenetic aging in Japanese medaka

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