Development of a novel aging clock based on chromatin accessibility

Rechsteiner, Cheyenne; Morandini, Francesco; Pérez, Kevin; Praz, Viviane; López-García, Guillermo; Hinte, Laura; Meyenn, Ferdinand von; Ocampo, Alejandro

doi:10.1101/2022.08.11.502778

Cited by 9 publications

(9 citation statements)

References 53 publications

(52 reference statements)

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“…Chromatin accessibility is an important indicator for assessing the degree of aging based on the "loss of heterochromatin" theory (Liu et al, 2022a;Pal and Tyler, 2016;Wang et al, 2022a;Wu et al, 2018;Zhang et al, 2015;Zhang et al, 2020d;Zhang et al, 2022e). Some novel chromatin accessibility-based aging clocks using bulk samples remain to be developed (Rechsteiner et al, 2022). The rapid progress of scATAC-seq sequencing technology has opened up a new era for the aging clock based on single-cell big data.…”

Section: Aging Clocks Based On Single-cell Epigenomementioning

confidence: 99%

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Biomarkers of aging

Bao

Cao

Chen

et al. 2023

Sci. China Life Sci.

117

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Aging biomarkers are a combination of biological parameters to (i) assess age-related changes, (ii) track the physiological aging process, and (iii) predict the transition into a pathological status. Although a broad spectrum of aging biomarkers has been developed, their potential uses and limitations remain poorly characterized. An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research: How old are we? Why do we get old? And how can we age slower? This review aims to address this need. Here, we summarize our current knowledge of biomarkers developed for cellular, organ, and organismal levels of aging, comprising six pillars: physiological characteristics, medical imaging, histological features, cellular alterations, molecular changes, and secretory factors. To fulfill all these requisites, we propose that aging biomarkers should qualify for being specific, systemic, and clinically relevant. Supporting Information The supporting information is available online at 10.1007/s11427-023-2305-0. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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Section: Aging Clocks Based On Single-cell Epigenomementioning

confidence: 99%

“…+ hematopoietic stem cells to determine cell age and perform lineage tracing (Rechsteiner et al, 2022). Current evidence suggests that methylation clocks hold the most promise for development and application.…”

Section: Aging Clocks Based On Single-cell Epigenomementioning

confidence: 99%

Biomarkers of aging

Bao

Cao

Chen

et al. 2023

Sci. China Life Sci.

117

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“…Previously, the foundation for epigenetic age predictors predominantly rested on DNA methylation. However, recent advancements have led to the inception of a model grounded in chromatin accessibility, which has shown promising results [51]. Until this study, a predictor based on histone marks was a void in the research domain.…”

Section: Discussionmentioning

confidence: 97%

Histone mark age of human tissues and cells

de Lima Camillo,

Asif,

Horvath

et al. 2023

Preprint

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Background: Aging involves intricate epigenetic changes, with histone modifications playing a pivotal role in dynamically regulating gene expression. Our research comprehensively analyzes seven key histone modifications across various tissues to understand their behavior during human aging and formulate age prediction models. Results: These histone-centric prediction models exhibit remarkable accuracy and resilience against experimental and artificial noise. They showcase comparable efficacy when compared with DNA methylation age predictors through simulation experiments. Intriguingly, our gene set enrichment analysis pinpoints vital developmental pathways crucial for age prediction. Unlike in DNA methylation age predictors, genes previously recognized in animal studies as integral to aging are amongst the most important features of our models. We also introduce a pan-histone-mark, pan-tissue age predictor that operates across multiple tissues and histone marks, reinforcing that age-related epigenetic markers are not restricted to particular histone modifications. Conclusion: Our findings underscore the potential of histone marks in crafting robust age predictors and shed light on the intricate tapestry of epigenetic alterations in aging.

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“…[36,37] Recently a novel epigenetic ageing clock was developed using chromatin accessibility profiles (ATAC-Seq) generated from peripheral blood mononuclear cells (PBMCs) isolated from young and old donors, which correlated with age-associated gene expression changes more significantly than the DNAm-based ageing clocks. [38] It would be interesting to correlate age-associated changes in histone modifications, chromatin accessibility, and DNAm, given the strong association between these regulatory pathways, [15,39] potentially leading to the development of more comprehensive epigenetic-ageing signatures.…”

Section: Resetting Other Types Of Epigenetic Marksmentioning

confidence: 99%

Epigenetic rejuvenation by partial reprogramming

Puri

Wagner

2023

BioEssays

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Rejuvenation of cells by reprogramming toward the pluripotent state raises increasing attention. In fact, generation of induced pluripotent stem cells (iPSCs) completely reverses age‐associated molecular features, including elongation of telomeres, resetting of epigenetic clocks and age‐associated transcriptomic changes, and even evasion of replicative senescence. However, reprogramming into iPSCs also entails complete de‐differentiation with loss of cellular identity, as well as the risk of teratoma formation in anti‐ageing treatment paradigms. Recent studies indicate that partial reprogramming by limited exposure to reprogramming factors can reset epigenetic ageing clocks while maintaining cellular identity. So far, there is no commonly accepted definition of partial reprogramming, which is alternatively called interrupted reprogramming, and it remains to be elucidated how the process can be controlled and if it resembles a stable intermediate state. In this review, we discuss if the rejuvenation program can be uncoupled from the pluripotency program or if ageing and cell fate determination are inextricably linked. Alternative rejuvenation approaches with reprogramming into a pluripotent state, partial reprogramming, transdifferentiation, and the possibility of selective resetting of cellular clocks are also discussed.

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Development of a novel aging clock based on chromatin accessibility

Cited by 9 publications

References 53 publications

Biomarkers of aging

Biomarkers of aging

Histone mark age of human tissues and cells

Epigenetic rejuvenation by partial reprogramming

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