Somatic mutation as an explanation for epigenetic aging
DNA methylation marks have recently been used to build models known as "epigenetic clocks" which predict calendar age. As methylation of cytosine promotes C-to-T mutations, we hypothesized that the methylation changes observed with age should reflect the accrual of somatic mutations, and the two should yield analogous aging estimates. In analysis of multimodal data from 9,331 human individuals, we find that CpG mutations indeed coincide with changes in methylation, not only at the mutated site but also with pervasive remodeling of the methylome out to ±10 kilobases. This one-to-many mapping enables mutation-based predictions of age that agree with epigenetic clocks, including which individuals are aging faster or slower than expected. Moreover, genomic loci where mutations accumulate with age also tend to have methylation patterns that are especially predictive of age. These results suggest a close coupling between the accumulation of sporadic somatic mutations and the widespread changes in methylation observed over the course of life.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
|---|---|
| Enthalten in: |
bioRxiv : the preprint server for biology - (2023) vom: 09. Dez. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Koch, Zane [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Revised 25.12.2023 published: Electronic Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.1101/2023.12.08.569638 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM365967890 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM365967890 | ||
| 003 | DE-627 | ||
| 005 | 20231227140957.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231227s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2023.12.08.569638 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1238.xml |
| 035 | |a (DE-627)NLM365967890 | ||
| 035 | |a (NLM)38106096 | ||
| 035 | |a (PII)2023.12.08.569638 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Koch, Zane |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Somatic mutation as an explanation for epigenetic aging |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 25.12.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a DNA methylation marks have recently been used to build models known as "epigenetic clocks" which predict calendar age. As methylation of cytosine promotes C-to-T mutations, we hypothesized that the methylation changes observed with age should reflect the accrual of somatic mutations, and the two should yield analogous aging estimates. In analysis of multimodal data from 9,331 human individuals, we find that CpG mutations indeed coincide with changes in methylation, not only at the mutated site but also with pervasive remodeling of the methylome out to ±10 kilobases. This one-to-many mapping enables mutation-based predictions of age that agree with epigenetic clocks, including which individuals are aging faster or slower than expected. Moreover, genomic loci where mutations accumulate with age also tend to have methylation patterns that are especially predictive of age. These results suggest a close coupling between the accumulation of sporadic somatic mutations and the widespread changes in methylation observed over the course of life | ||
| 650 | 4 | |a Preprint | |
| 700 | 1 | |a Li, Adam |e verfasserin |4 aut | |
| 700 | 1 | |a Evans, Daniel S |e verfasserin |4 aut | |
| 700 | 1 | |a Cummings, Steven |e verfasserin |4 aut | |
| 700 | 1 | |a Ideker, Trey |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv : the preprint server for biology |d 2020 |g (2023) vom: 09. Dez. |w (DE-627)NLM31090014X |7 nnns |
| 773 | 1 | 8 | |g year:2023 |g day:09 |g month:12 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2023.12.08.569638 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2023 |b 09 |c 12 | ||