Cell-type specific epigenetic clocks to quantify biological age at cell-type resolution DOI Creative Commons
Huige Tong, Xiaolong Guo, Macsue Jacques

et al.

Aging, Journal Year: 2024, Volume and Issue: 16(22), P. 13452 - 13504

Published: Dec. 29, 2024

The ability to accurately quantify biological age could help monitor and control healthy aging. Epigenetic clocks have emerged as promising tools for estimating age, yet they been developed from heterogeneous bulk tissues, are thus composites of two aging processes, one reflecting the change cell-type composition with another individual cell-types. There is a need dissect these components epigenetic clocks, develop that can yield estimates at resolution. Here we demonstrate in blood brain, approximately 39% 12% an clock's accuracy driven by underlying shifts lymphocyte neuronal subsets, respectively. Using brain liver tissue prototypes, build validate neuron hepatocyte specific DNA methylation improved chronological corresponding cell tissue-types. We find glia display acceleration Alzheimer's Disease effect being strongest temporal lobe. Moreover, CpGs small but significant overlap causal DamAge-clock, mapping key genes implicated neurodegeneration. clock found accelerated under various pathological conditions. In contrast, non-cell-type do not age-acceleration, or only so marginally. summary, this work highlights importance dissecting quantifying

Language: Английский

rDNA Copy Number Variation and Methylation During Normal and Premature Aging DOI Creative Commons

Alva B. C. Geisen,

Nathalie Acevedo, Junko Oshima

et al.

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

ABSTRACT Ribosomal RNA is the main component of ribosome, which essential for protein synthesis. The diploid human genome contains several hundred copies rDNA transcription unit (TU). Droplet digital PCR and deep bisulfite sequencing were used to determine absolute copy number (CN) methylation status individual TU in blood samples healthy individuals. CN ranged from 243 895 (median 469). There was no difference between males females gain or loss with age (15–71 years). a completely unmethylated (0%) lowly methylated (1%–10%) promoter region significantly decreased, whereas higher (11%–100%) increased age. presumably active hypomethylated (0%–10%) varied 94 277 180), independent CN. In contrast, inactive hypermethylated strongly Promoter hypermethylation compensates some extent enormous variation among Patients Werner syndrome, premature aging syndrome displayed same age‐related changes as controls. role modulating factor health disease largely unexplored. particular, very low high may be associated risk.

Language: Английский

Citations

0
DNA methylation differences between cord and adult white blood cells reflect postnatal immune cell maturation DOI Creative Commons
Meaghan J. Jones, Chaini Konwar, Rebecca Asiimwe

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Feb. 14, 2025

Epigenetic modifications such as DNA methylation are both cell type and developmental age specific. Here, we show that the immunological maturation of blood types influences changes from naive cord to fully functional adult blood. Lymphoid cells in showed more variability than suggesting an antigen-dependent lymphoid throughout lifespan. Fewer between were observed myeloid cells, particularly monocytes, which demonstrated least number We also noted differences epigenetic ages by immune within same individuals, specifically where monocytes epigenetically oldest compared other types. In addition, provide a publicly available resource community R Shiny web application interactively explore patterns white for six Comparison profiles isolated reveals develop antigen-driven during maturation, while especially stable.

Language: Английский

Citations

0
Immune cell composition is an important contributor to epigenetic age variation DOI Creative Commons
Saara Marttila

Epigenomics, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 3

Published: March 6, 2025

KEYWORDS: Epigenetic ageepigenetic clockepigenetic age deviationbiological ageDNA methylationimmune cellimmune cell composition

Citations

0
Cell-type specific epigenetic clocks to quantify biological age at cell-type resolution DOI Creative Commons
Huige Tong, Xiaolong Guo, Macsue Jacques

et al.

Aging, Journal Year: 2024, Volume and Issue: 16(22), P. 13452 - 13504

Published: Dec. 29, 2024

The ability to accurately quantify biological age could help monitor and control healthy aging. Epigenetic clocks have emerged as promising tools for estimating age, yet they been developed from heterogeneous bulk tissues, are thus composites of two aging processes, one reflecting the change cell-type composition with another individual cell-types. There is a need dissect these components epigenetic clocks, develop that can yield estimates at resolution. Here we demonstrate in blood brain, approximately 39% 12% an clock's accuracy driven by underlying shifts lymphocyte neuronal subsets, respectively. Using brain liver tissue prototypes, build validate neuron hepatocyte specific DNA methylation improved chronological corresponding cell tissue-types. We find glia display acceleration Alzheimer's Disease effect being strongest temporal lobe. Moreover, CpGs small but significant overlap causal DamAge-clock, mapping key genes implicated neurodegeneration. clock found accelerated under various pathological conditions. In contrast, non-cell-type do not age-acceleration, or only so marginally. summary, this work highlights importance dissecting quantifying

Language: Английский

Citations

1