Epigenetic clocks galore: a new improved clock predicts age-acceleration in Hutchinson Gilford Progeria Syndrome patients

Teschendorff, Andrew E.

doi:10.18632/aging.101533

Cited by 4 publications

(3 citation statements)

References 9 publications

(3 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For full evaluation, this may require single-cell bisulfite sequencing (scBS-seq) studies, nanopore sequencing analysis, and further technological advancement to be fully realized (discussed in “Challenge 5”). These tissue- and disease-specific clocks in isolated cell types or cell type-aware analyses could enable greater insights into the molecular drivers of biological aging [97]. These processes need to be explored across all organ systems, to identify not only specific but also common mechanisms.…”

Section: Challengementioning

confidence: 99%

DNA methylation aging clocks: challenges and recommendations

et al. 2019

Self Cite

View full text Add to dashboard Buy / Rent full text

Epigenetic clocks comprise a set of CpG sites whose DNA methylation levels measure subject age. These clocks are acknowledged as a highly accurate molecular correlate of chronological age in humans and other vertebrates. Also, extensive research is aimed at their potential to quantify biological aging rates and test longevity or rejuvenating interventions. Here, we discuss key challenges to understand clock mechanisms and biomarker utility. This requires dissecting the drivers and regulators of age-related changes in single-cell, tissue- and disease-specific models, as well as exploring other epigenomic marks, longitudinal and diverse population studies, and non-human models. We also highlight important ethical issues in forensic age determination and predicting the trajectory of biological aging in an individual.

show abstract

Section: Challengementioning

confidence: 99%

DNA methylation aging clocks: challenges and recommendations

et al. 2019

Self Cite

View full text Add to dashboard Buy / Rent full text

show abstract

“…Hence, several observations support the use of DNAm age as a new and promising indicator of biological aging [37][38][39]. In 2018, Horvath's clock was updated allowing for a more accurate estimation of the chronological age by using a variety of different tissues, including whole blood ("Skin and Blood Clock") [40,41].…”

Section: Introductionmentioning

confidence: 99%

Idiopathic early ovarian aging: is there a relation with premenopausal accelerated biological aging in young women with diminished response to ART?

Christensen¹,

Keefe

Wang

et al. 2021

J Assist Reprod Genet

View full text Add to dashboard Buy / Rent full text

Purpose To evaluate whether young women with idiopathic early ovarian aging, as defined by producing fewer oocytes than expected for a given age over multiple in vitro fertilization (IVF) cycles, have changes in telomere length and epigenetic age indicating accelerated biological aging (i.e., increased risk of morbidity and mortality). Methods A prospective cohort study was conducted at two Danish public fertility clinics. A total of 55 young women (≤ 37 years) with at least two IVF cycles with ≤ 5 harvested oocytes despite sufficient stimulation with follicle-stimulating hormone (FSH) were included in the early ovarian aging group. As controls, 52 young women (≤ 37 years) with normal ovarian function, defined by at least eight harvested oocytes, were included. Relative telomere length (rTL) and epigenetic age acceleration (AgeAccel) were measured in white blood cells as markers of premenopausal accelerated biological aging. Results rTL was comparable with a mean of 0.46 (± SD 0.12) in the early ovarian aging group and 0.47 (0.14) in the normal ovarian aging group. The AgeAccel of the early ovarian aging group was, insignificantly, 0.5 years older, but this difference disappeared when adjusting for chronological age. Sub-analysis using Anti-Müllerian hormone (AMH) as selection criterion for the two groups did not change the results. ConclusionWe did not find any indications of accelerated aging in whole blood from young women with idiopathic early ovarian aging. Further investigations in a similar cohort of premenopausal women or other tissues are needed to fully elucidate the potential relationship between premenopausal accelerated biological aging and early ovarian aging.

show abstract

“…To date, many other DNA methylation clocks have been developed for different purposes and tissue targets. 3,4,6–18 Since their inception, epigenetic clocks have been used to analyze DNA methylation profiles of diverse human cohorts, uncovering previously unknown associations between accelerated ageing and a great number of health-related features. 19,20 These associations indicate that epigenetic clocks do not just track chronological age, but also biological features that are relevant to the ageing process.…”

Section: Introductionmentioning

confidence: 99%

Current perspectives on the cellular and molecular features of epigenetic ageing

Raj

Horvath

2020

Exp Biol Med (Maywood)

View full text Add to dashboard Buy / Rent full text

It has been noted for quite some time that DNA methylation levels decline with age. The significance of this change remained unknown until it became possible to measure methylation status of specific sites on the DNA. It was observed that while the methylation of some sites does indeed decrease with age, that of others increase or remain unchanged. The application of machine learning methods to these quantitative changes in multiple sites, allowed the generation of a highly accurate estimator of age, called the epigenetic clock. The application of this clock on large human epidemiological data sets revealed that discordance between the predicted (epigenetic age) and chronological age is associated with many age-related pathologies, particularly when the former is greater than the latter. The epigenetic clock clearly captures to some degree, biological features that accompany the ageing process. Despite the ever-increasing scope of pathologies that are found to be associated with accelerated epigenetic ageing, the basic principles that underlie the ticking of the clock remain elusive. Here, we describe the known molecular and cellular attributes of the clock and consider their properties, and proffer opinions as to how they may be connected and what might be the underlying mechanism. Emerging from these considerations is the inescapable view that epigenetic ageing begins from very early moments after the embryonic stem cell stage and continues un-interrupted through the entire life-course. This appears to be a consequence of processes that are necessary for the development of the organism from conception and to maintain it thereafter through homeostasis. Hence, while the speed of ageing can, and is affected by external factors, the essence of the ageing process itself is an integral part of, and the consequence of the development of life. Impact statement The field of epigenetic ageing is relatively new, and the speed of its expansion presents a challenge in keeping abreast with new discoveries and their implications. Several reviews have already addressed the great number of pathologies, health conditions, life-style, and external stressors that are associated with changes to the rate of epigenetic ageing. While these associations highlight and affirm the ability of epigenetic clock to capture biologically meaningful changes associated with age, they do not inform us about the underlying mechanisms. In this very early period since the development of the clock, there have been rather limited experimental research that are aimed at uncovering the mechanism. Hence, the perspective that we proffer is derived from available but nevertheless limited lines of evidence that together provide a seemingly coherent narrative that can be tested. This, we believe would be helpful towards uncovering the workings of the epigenetic clock.

show abstract

Epigenetic clocks galore: a new improved clock predicts age-acceleration in Hutchinson Gilford Progeria Syndrome patients

Cited by 4 publications

References 9 publications

DNA methylation aging clocks: challenges and recommendations

DNA methylation aging clocks: challenges and recommendations

Idiopathic early ovarian aging: is there a relation with premenopausal accelerated biological aging in young women with diminished response to ART?

Current perspectives on the cellular and molecular features of epigenetic ageing

Contact Info

Product

Resources

About