Cell Tree Rings: the structure of somatic evolution as a human
aging timer

J 2024

Cell Tree Rings: the structure of somatic evolution as a human aging timer

CSORDAS, Attila; Botond SIPOS; Terézia KURUCOVÁ; Andrea VOLFOVA; Frantisek ZAMOLA et. al.

Basic information

Original name

Cell Tree Rings: the structure of somatic evolution as a human aging timer

Authors

CSORDAS, Attila (guarantor); Botond SIPOS; Terézia KURUCOVÁ (703 Slovakia, belonging to the institution); Andrea VOLFOVA; Frantisek ZAMOLA; Boris TICHÝ (203 Czech Republic, belonging to the institution) and Damien G HICKS

Edition

GEROSCIENCE, DORDRECHT, SPRINGER, 2024, 2509-2715

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

10605 Developmental biology

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 5.400

RIV identification code

RIV/00216224:14740/24:00135516

Organization unit

Central European Institute of Technology

DOI

https://doi.org/10.1007/s11357-023-01053-4

UT WoS

001135619600001

EID Scopus

2-s2.0-85181475590

Keywords in English

Cell Tree Rings; Geroprotective trials; Biological age

Abstract

In the original language

Biological age is typically estimated using biomarkers whose states have been observed to correlate with chronological age. A persistent limitation of such aging clocks is that it is difficult to establish how the biomarker states are related to the mechanisms of aging. Somatic mutations could potentially form the basis for a more fundamental aging clock since the mutations are both markers and drivers of aging and have a natural timescale. Cell lineage trees inferred from these mutations reflect the somatic evolutionary process, and thus, it has been conjectured, the aging status of the body. Such a timer has been impractical thus far, however, because detection of somatic variants in single cells presents a significant technological challenge. Here, we show that somatic mutations detected using single-cell RNA sequencing (scRNA-seq) from thousands of cells can be used to construct a cell lineage tree whose structure correlates with chronological age. De novo single-nucleotide variants (SNVs) are detected in human peripheral blood mononuclear cells using a modified protocol. A default model based on penalized multiple regression of chronological age on 31 metrics characterizing the phylogenetic tree gives a Pearson correlation of 0.81 and a median absolute error of similar to 4 years between predicted and chronological ages. Testing of the model on a public scRNA-seq dataset yields a Pearson correlation of 0.85. In addition, cell tree age predictions are found to be better predictors of certain clinical biomarkers than chronological age alone, for instance glucose, albumin levels, and leukocyte count. The geometry of the cell lineage tree records the structure of somatic evolution in the individual and represents a new modality of aging timer. In addition to providing a numerical estimate of "cell tree age," it unveils a temporal history of the aging process, revealing how clonal structure evolves over life span. Cell Tree Rings complements existing aging clocks and may help reduce the current uncertainty in the assessment of geroprotective trials.

Links

90267, large research infrastructures

Name: NCMG III

Cite

CSORDAS, Attila; Botond SIPOS; Terézia KURUCOVÁ; Andrea VOLFOVA; Frantisek ZAMOLA; Boris TICHÝ and Damien G HICKS. Cell Tree Rings: the structure of somatic evolution as a human aging timer. GEROSCIENCE. DORDRECHT: SPRINGER, 2024, vol. 46, No 3, p. 3005-3019. ISSN 2509-2715. Available from: https://doi.org/10.1007/s11357-023-01053-4.

@article{2373918,
   author = {Csordas, Attila and Sipos, Botond and Kurucová, Terézia and Volfova, Andrea and Zamola, Frantisek and Tichý, Boris and Hicks, Damien G},
   article_location = {DORDRECHT},
   article_number = {3},
   doi = {https://doi.org/10.1007/s11357-023-01053-4},
   keywords = {Cell Tree Rings; Geroprotective trials; Biological age},
   language = {eng},
   issn = {2509-2715},
   journal = {GEROSCIENCE},
   title = {Cell Tree Rings: the structure of somatic evolution as a human aging timer},
   url = {https://link.springer.com/article/10.1007/s11357-023-01053-4},
   volume = {46},
   year = {2024}
}

TY  - JOUR
ID  - 2373918
AU  - Csordas, Attila - Sipos, Botond - Kurucová, Terézia - Volfova, Andrea - Zamola, Frantisek - Tichý, Boris - Hicks, Damien G
PY  - 2024
TI  - Cell Tree Rings: the structure of somatic evolution as a human aging timer
JF  - GEROSCIENCE
VL  - 46
IS  - 3
SP  - 3005-3019
EP  - 3005-3019
PB  - SPRINGER
SN  - 25092715
KW  - Cell Tree Rings
KW  - Geroprotective trials
KW  - Biological age
UR  - https://link.springer.com/article/10.1007/s11357-023-01053-4
N2  - Biological age is typically estimated using biomarkers whose states have been observed to correlate with chronological age. A persistent limitation of such aging clocks is that it is difficult to establish how the biomarker states are related to the mechanisms of aging. Somatic mutations could potentially form the basis for a more fundamental aging clock since the mutations are both markers and drivers of aging and have a natural timescale. Cell lineage trees inferred from these mutations reflect the somatic evolutionary process, and thus, it has been conjectured, the aging status of the body. Such a timer has been impractical thus far, however, because detection of somatic variants in single cells presents a significant technological challenge. Here, we show that somatic mutations detected using single-cell RNA sequencing (scRNA-seq) from thousands of cells can be used to construct a cell lineage tree whose structure correlates with chronological age. De novo single-nucleotide variants (SNVs) are detected in human peripheral blood mononuclear cells using a modified protocol. A default model based on penalized multiple regression of chronological age on 31 metrics characterizing the phylogenetic tree gives a Pearson correlation of 0.81 and a median absolute error of similar to 4 years between predicted and chronological ages. Testing of the model on a public scRNA-seq dataset yields a Pearson correlation of 0.85. In addition, cell tree age predictions are found to be better predictors of certain clinical biomarkers than chronological age alone, for instance glucose, albumin levels, and leukocyte count. The geometry of the cell lineage tree records the structure of somatic evolution in the individual and represents a new modality of aging timer. In addition to providing a numerical estimate of "cell tree age," it unveils a temporal history of the aging process, revealing how clonal structure evolves over life span. Cell Tree Rings complements existing aging clocks and may help reduce the current uncertainty in the assessment of geroprotective trials.
ER  -

CSORDAS, Attila; Botond SIPOS; Terézia KURUCOVÁ; Andrea VOLFOVA; Frantisek ZAMOLA; Boris TICHÝ and Damien G HICKS. Cell Tree Rings: the structure of somatic evolution as a human aging timer. \textit{GEROSCIENCE}. DORDRECHT: SPRINGER, 2024, vol.~46, No~3, p.~3005-3019. ISSN~2509-2715. Available from: https://doi.org/10.1007/s11357-023-01053-4.

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