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.

Základní údaje

Originální název

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

Autoři

CSORDAS, Attila (garant), Botond SIPOS, Terézia KURUCOVÁ (703 Slovensko, domácí), Andrea VOLFOVA, Frantisek ZAMOLA, Boris TICHÝ (203 Česká republika, domácí) a Damien G HICKS

Vydání

GEROSCIENCE, DORDRECHT, SPRINGER, 2024, 2509-2715

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10605 Developmental biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.600 v roce 2022

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1007/s11357-023-01053-4

UT WoS

001135619600001

Klíčová slova anglicky

Cell Tree Rings; Geroprotective trials; Biological age

Štítky

CF GEN, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 8. 4. 2024 09:59, Mgr. Eva Dubská

Anotace

V originále

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.

Návaznosti

90267, velká výzkumná infrastruktura

Název: NCMG III

Citovat

CSORDAS, Attila, Botond SIPOS, Terézia KURUCOVÁ, Andrea VOLFOVA, Frantisek ZAMOLA, Boris TICHÝ a Damien G HICKS. Cell Tree Rings: the structure of somatic evolution as a human aging timer. GEROSCIENCE. DORDRECHT: SPRINGER, 2024, roč. 2024, Jan, s. 1-15. ISSN 2509-2715. Dostupné z: https://dx.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 = {Jan},
   doi = {http://dx.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 = {2024},
   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  - 2024
IS  - Jan
SP  - 1-15
EP  - 1-15
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 a Damien G HICKS. Cell Tree Rings: the structure of somatic evolution as a human aging timer. \textit{GEROSCIENCE}. DORDRECHT: SPRINGER, 2024, roč.~2024, Jan, s.~1-15. ISSN~2509-2715. Dostupné z: https://dx.doi.org/10.1007/s11357-023-01053-4.

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