Neuron-specific chromatin disruption at CpG islands and aging-related regions in Kabuki syndrome mice DOI Creative Commons
Leandros Boukas, Teresa Romeo Luperchio, Afrooz Razi

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Авг. 3, 2023

Many Mendelian developmental disorders caused by coding variants in epigenetic regulators have now been discovered. Epigenetic are broadly expressed, and each of these typically exhibits phenotypic manifestations from many different organ systems. An open question is whether the chromatin disruption - root pathogenesis similar disease-relevant cell types. This possible principle, since all cell-types subject to effects same causative gene, that has kind function (e.g. methylates histones) disrupted germline variant. We focus on mouse models for Kabuki syndrome types 1 2, find accessibility abnormalities neurons mostly distinct those B or T cells. not because neuronal occur at regulatory elements only active neurons. Neurons, but cells, show preferential CpG islands linked aging. A sensitive analysis reveals regions B/T cells do exhibit changes neurons, very subtle uncertain functional significance. Finally, we able identify a small set three Our findings reveal cellular-context-specific effect regulators, suggest blood-derived "episignatures" may be well-suited understanding mechanistic basis neurodevelopment machinery.

Язык: Английский

Nature of epigenetic aging from a single-cell perspective DOI
Andrei E. Tarkhov,

Thomas Lindstrom-Vautrin,

Sirui Zhang

и другие.

Nature Aging, Год журнала: 2024, Номер 4(6), С. 854 - 870

Опубликована: Май 9, 2024

Язык: Английский

Процитировано

29
The long and winding road of reprogramming-induced rejuvenation DOI Creative Commons
Ali D. Yucel, Vadim N. Gladyshev

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 2, 2024

Abstract Organismal aging is inherently connected to the of its constituent cells and systems. Reducing biological age organism may be assisted by reducing - an approach exemplified partial cell reprogramming through expression Yamanaka factors or exposure chemical cocktails. It crucial protect type identity during reprogramming, as need retain rapidly regain their functions following treatment. Another critical issue ability quantify reprogrammed older acquire younger states. We discuss recent advances in reprogramming-induced rejuvenation offer a review this procedure relationship fundamental nature aging. further comparatively analyze full transdifferentiation approaches, assess safety concerns emphasize importance distinguishing from dedifferentiation. Finally, we highlight translational opportunities that offers.

Язык: Английский

Процитировано

13
Nature of epigenetic aging from a single-cell perspective DOI Creative Commons
Andrei E. Tarkhov,

Thomas Lindstrom-Vautrin,

Sirui Zhang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Сен. 28, 2022

Abstract Age-related changes in DNA methylation (DNAm) form the basis for development of most robust predictors age, epigenetic clocks, but a clear mechanistic exactly what part aging process they quantify is lacking. Here, to clarify nature aging, we juxtapose dynamics tissue and single-cell DNAm (scDNAm) with scDNAm during early development, corroborate our analyses RNAseq analysis within same multi-omics dataset. We show that involves co-regulated changes, it dominated by stochastic component, this agrees transcriptional coordination patterns. further support finding direct modeling trajectories akin radiocarbon decay. Finally, describe algorithm identification CpG clusters showing consistent transcriptomic patterns, providing new opportunities targeting evaluating longevity interventions.

Язык: Английский

Процитировано

16
Axolotl epigenetic clocks offer insights into the nature of negligible senescence DOI

Yuliia Haluza,

Joseph A. Zoller, Ake T. Lu

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 10, 2024

Renowned for their regenerative abilities, axolotls also exhibit exceptional longevity, resistance to age-related diseases and apparent lack of physiological declines through lifespan, have thus been considered organisms negligible senescence. Whether display epigenetic hallmarks ageing remains unknown. Here, we probe the axolotl DNA methylome throughout lifespan present its first clocks. Both at tissue-specific or pan-tissue levels, clocks are biphasic, capable predicting age during early life but not rest lifespan. We show that evolutionarily conserved features life, yet is remarkably stable across including Polycomb Repressive Complex 2 (PRC2) target sites, suggesting this species deviates from known patterns ageing. Lastly, uncover structure-specific rejuvenation events upon regeneration. This study provides molecular insights into senescence furthers our understanding interplay between regeneration

Язык: Английский

Процитировано

2
Somatic mutation as an explanation for epigenetic aging DOI Creative Commons
Zane Koch, Adam Li, Daniel S. Evans

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Дек. 9, 2023

Abstract DNA methylation marks have recently been used to build models known as “epigenetic clocks” which predict calendar age. As of cytosine promotes C-to-T mutations, we hypothesized that the changes observed with age should reflect accrual somatic and two yield analogous aging estimates. In analysis multimodal data from 9,331 human individuals, find CpG mutations indeed coincide in methylation, not only at mutated site but also pervasive remodeling methylome out ±10 kilobases. This one-to-many mapping enables mutation-based predictions agree epigenetic clocks, including individuals are faster or slower than expected. Moreover, genomic loci where accumulate tend patterns especially predictive These results suggest a close coupling between accumulation sporadic widespread over course life.

Язык: Английский

Процитировано

3
Neuron-specific chromatin disruption at CpG islands and aging-related regions in Kabuki syndrome mice DOI
Leandros Boukas, Teresa Romeo Luperchio, Afrooz Razi

и другие.

Genome Research, Год журнала: 2024, Номер 34(5), С. 696 - 710

Опубликована: Май 1, 2024

Many Mendelian developmental disorders caused by coding variants in epigenetic regulators have now been discovered. Epigenetic are broadly expressed, and each of these typically shows phenotypic manifestations from many different organ systems. An open question is whether the chromatin disruption—the root pathogenesis—is similar disease-relevant cell types. This possible principle, because all types subject to effects same causative gene, which has kind function (e.g., methylates histones) disrupted germline variant. We focus on mouse models for Kabuki syndrome 1 2 find that accessibility changes neurons mostly distinct B or T cells. not neuronal occur at regulatory elements only active neurons. Neurons, but cells, show preferential disruption CpG islands linked aging. A sensitive analysis reveals B/T cells do neurons, very subtle uncertain functional significance. Finally, we able identify a small set three Our findings reveal cellular-context-specific effect suggest blood-derived episignatures, although useful diagnostically, may be well suited understanding mechanistic basis neurodevelopment machinery.

Язык: Английский

Процитировано

0
Neuron-specific chromatin disruption at CpG islands and aging-related regions in Kabuki syndrome mice DOI Creative Commons
Leandros Boukas, Teresa Romeo Luperchio, Afrooz Razi

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Авг. 3, 2023

Many Mendelian developmental disorders caused by coding variants in epigenetic regulators have now been discovered. Epigenetic are broadly expressed, and each of these typically exhibits phenotypic manifestations from many different organ systems. An open question is whether the chromatin disruption - root pathogenesis similar disease-relevant cell types. This possible principle, since all cell-types subject to effects same causative gene, that has kind function (e.g. methylates histones) disrupted germline variant. We focus on mouse models for Kabuki syndrome types 1 2, find accessibility abnormalities neurons mostly distinct those B or T cells. not because neuronal occur at regulatory elements only active neurons. Neurons, but cells, show preferential CpG islands linked aging. A sensitive analysis reveals regions B/T cells do exhibit changes neurons, very subtle uncertain functional significance. Finally, we able identify a small set three Our findings reveal cellular-context-specific effect regulators, suggest blood-derived "episignatures" may be well-suited understanding mechanistic basis neurodevelopment machinery.

Язык: Английский

Процитировано

1