Proteomes of primary skin fibroblasts from healthy individuals reveal altered cell responses across the life span

Dimitrios Tsitsipatis; Jennifer L. Martindale; Ceereena Ubaida-Mohien; Alexey Lyashkov; Hagai Yanai; Amogh Kashyap; Chang Hoon Shin; Allison B. Herman; Eunbyul Ji; Jen Hao Yang; Rachel Munk; Christopher Dunn; Yevgeniya Lukyanenko; Xiaoling Yang; Chee W. Chia; Ajoy C. Karikkineth; Linda Zukley; Jarod D’Agostino; Mary Kaileh; Chang Yi Cui; Isabel Beerman; Luigi Ferrucci; Myriam Gorospe

doi:10.1111/acel.13609

Proteomes of primary skin fibroblasts from healthy individuals reveal altered cell responses across the life span

Dimitrios Tsitsipatis, Jennifer L. Martindale, Ceereena Ubaida-Mohien, Alexey Lyashkov, Hagai Yanai, Amogh Kashyap, Chang Hoon Shin, Allison B. Herman, Eunbyul Ji, Jen Hao Yang, Rachel Munk, Christopher Dunn, Yevgeniya Lukyanenko, Xiaoling Yang, Chee W. Chia, Ajoy C. Karikkineth, Linda Zukley, Jarod D’Agostino, Mary Kaileh, Chang Yi CuiIsabel Beerman, Luigi Ferrucci, Myriam Gorospe

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Changes in the proteome of different human tissues with advancing age are poorly characterized. Here, we studied the proteins present in primary skin fibroblasts collected from 82 healthy individuals across a wide age spectrum (22–89 years old) who participated in the GESTALT (Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing) study of the National Institute on Aging, NIH. Proteins were extracted from lysed fibroblasts and subjected to liquid chromatography-mass spectrometry analysis, and the expression levels of 9341 proteins were analyzed using linear regression models. We identified key pathways associated with skin fibroblast aging, including autophagy, scavenging of reactive oxygen species (ROS), ribosome biogenesis, DNA replication, and DNA repair. Changes in these prominent pathways were corroborated using molecular and cell culture approaches. Our study establishes a framework of the global proteome governing skin fibroblast aging and points to possible biomarkers and therapeutic targets.

Original language	English
Article number	e13609
Journal	Aging Cell
Volume	21
Issue number	5
DOIs	https://doi.org/10.1111/acel.13609
State	Published - 1 May 2022
Externally published	Yes

Keywords

DNA damage
DNA repair
aging
autophagy
human dermal fibroblasts
proteomics
reactive oxygen species
ribosome biogenesis

ASJC Scopus subject areas

Aging
Cell Biology

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10.1111/acel.13609

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Tsitsipatis, D., Martindale, J. L., Ubaida-Mohien, C., Lyashkov, A., Yanai, H., Kashyap, A., Shin, C. H., Herman, A. B., Ji, E., Yang, J. H., Munk, R., Dunn, C., Lukyanenko, Y., Yang, X., Chia, C. W., Karikkineth, A. C., Zukley, L., D’Agostino, J., Kaileh, M., ... Gorospe, M. (2022). Proteomes of primary skin fibroblasts from healthy individuals reveal altered cell responses across the life span. Aging Cell, 21(5), Article e13609. https://doi.org/10.1111/acel.13609

@article{6b119c1ed2f14f6b8ca40956af635ea6,

title = "Proteomes of primary skin fibroblasts from healthy individuals reveal altered cell responses across the life span",

abstract = "Changes in the proteome of different human tissues with advancing age are poorly characterized. Here, we studied the proteins present in primary skin fibroblasts collected from 82 healthy individuals across a wide age spectrum (22–89 years old) who participated in the GESTALT (Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing) study of the National Institute on Aging, NIH. Proteins were extracted from lysed fibroblasts and subjected to liquid chromatography-mass spectrometry analysis, and the expression levels of 9341 proteins were analyzed using linear regression models. We identified key pathways associated with skin fibroblast aging, including autophagy, scavenging of reactive oxygen species (ROS), ribosome biogenesis, DNA replication, and DNA repair. Changes in these prominent pathways were corroborated using molecular and cell culture approaches. Our study establishes a framework of the global proteome governing skin fibroblast aging and points to possible biomarkers and therapeutic targets.",

keywords = "DNA damage, DNA repair, aging, autophagy, human dermal fibroblasts, proteomics, reactive oxygen species, ribosome biogenesis",

author = "Dimitrios Tsitsipatis and Martindale, {Jennifer L.} and Ceereena Ubaida-Mohien and Alexey Lyashkov and Hagai Yanai and Amogh Kashyap and Shin, {Chang Hoon} and Herman, {Allison B.} and Eunbyul Ji and Yang, {Jen Hao} and Rachel Munk and Christopher Dunn and Yevgeniya Lukyanenko and Xiaoling Yang and Chia, {Chee W.} and Karikkineth, {Ajoy C.} and Linda Zukley and Jarod D{\textquoteright}Agostino and Mary Kaileh and Cui, {Chang Yi} and Isabel Beerman and Luigi Ferrucci and Myriam Gorospe",

note = "Publisher Copyright: Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.",

year = "2022",

month = may,

day = "1",

doi = "10.1111/acel.13609",

language = "English",

volume = "21",

journal = "Aging Cell",

issn = "1474-9718",

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Tsitsipatis, D, Martindale, JL, Ubaida-Mohien, C, Lyashkov, A, Yanai, H, Kashyap, A, Shin, CH, Herman, AB, Ji, E, Yang, JH, Munk, R, Dunn, C, Lukyanenko, Y, Yang, X, Chia, CW, Karikkineth, AC, Zukley, L, D’Agostino, J, Kaileh, M, Cui, CY, Beerman, I, Ferrucci, L & Gorospe, M 2022, 'Proteomes of primary skin fibroblasts from healthy individuals reveal altered cell responses across the life span', Aging Cell, vol. 21, no. 5, e13609. https://doi.org/10.1111/acel.13609

TY - JOUR

T1 - Proteomes of primary skin fibroblasts from healthy individuals reveal altered cell responses across the life span

AU - Tsitsipatis, Dimitrios

AU - Martindale, Jennifer L.

AU - Ubaida-Mohien, Ceereena

AU - Lyashkov, Alexey

AU - Yanai, Hagai

AU - Kashyap, Amogh

AU - Shin, Chang Hoon

AU - Herman, Allison B.

AU - Ji, Eunbyul

AU - Yang, Jen Hao

AU - Munk, Rachel

AU - Dunn, Christopher

AU - Lukyanenko, Yevgeniya

AU - Yang, Xiaoling

AU - Chia, Chee W.

AU - Karikkineth, Ajoy C.

AU - Zukley, Linda

AU - D’Agostino, Jarod

AU - Kaileh, Mary

AU - Cui, Chang Yi

AU - Beerman, Isabel

AU - Ferrucci, Luigi

AU - Gorospe, Myriam

N1 - Publisher Copyright: Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.

PY - 2022/5/1

Y1 - 2022/5/1

N2 - Changes in the proteome of different human tissues with advancing age are poorly characterized. Here, we studied the proteins present in primary skin fibroblasts collected from 82 healthy individuals across a wide age spectrum (22–89 years old) who participated in the GESTALT (Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing) study of the National Institute on Aging, NIH. Proteins were extracted from lysed fibroblasts and subjected to liquid chromatography-mass spectrometry analysis, and the expression levels of 9341 proteins were analyzed using linear regression models. We identified key pathways associated with skin fibroblast aging, including autophagy, scavenging of reactive oxygen species (ROS), ribosome biogenesis, DNA replication, and DNA repair. Changes in these prominent pathways were corroborated using molecular and cell culture approaches. Our study establishes a framework of the global proteome governing skin fibroblast aging and points to possible biomarkers and therapeutic targets.

AB - Changes in the proteome of different human tissues with advancing age are poorly characterized. Here, we studied the proteins present in primary skin fibroblasts collected from 82 healthy individuals across a wide age spectrum (22–89 years old) who participated in the GESTALT (Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing) study of the National Institute on Aging, NIH. Proteins were extracted from lysed fibroblasts and subjected to liquid chromatography-mass spectrometry analysis, and the expression levels of 9341 proteins were analyzed using linear regression models. We identified key pathways associated with skin fibroblast aging, including autophagy, scavenging of reactive oxygen species (ROS), ribosome biogenesis, DNA replication, and DNA repair. Changes in these prominent pathways were corroborated using molecular and cell culture approaches. Our study establishes a framework of the global proteome governing skin fibroblast aging and points to possible biomarkers and therapeutic targets.

KW - DNA damage

KW - DNA repair

KW - aging

KW - autophagy

KW - human dermal fibroblasts

KW - proteomics

KW - reactive oxygen species

KW - ribosome biogenesis

UR - http://www.scopus.com/inward/record.url?scp=85128207877&partnerID=8YFLogxK

U2 - 10.1111/acel.13609

DO - 10.1111/acel.13609

M3 - Article

C2 - 35429111

AN - SCOPUS:85128207877

SN - 1474-9718

VL - 21

JO - Aging Cell

JF - Aging Cell

IS - 5

M1 - e13609

ER -

Proteomes of primary skin fibroblasts from healthy individuals reveal altered cell responses across the life span

Abstract

Keywords

ASJC Scopus subject areas

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