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

被引：10

作者：

Tsitsipatis, Dimitrios ^{[1
]}

Martindale, Jennifer L. ^{[1
]}

Ubaida-Mohien, Ceereena ^{[2
]}

Lyashkov, Alexey ^{[2
]}

Yanai, Hagai ^{[2
]}

Kashyap, Amogh ^{[2
]}

Shin, Chang Hoon ^{[1
]}

Herman, Allison B. ^{[1
]}

Ji, Eunbyul ^{[1
]}

Yang, Jen-Hao ^{[1
]}

Munk, Rachel ^{[1
]}

Dunn, Christopher ^{[3
]}

Lukyanenko, Yevgeniya ^{[2
]}

Yang, Xiaoling ^{[1
]}

Chia, Chee W. ^{[4
]}

Karikkineth, Ajoy C. ^{[4
]}

Zukley, Linda ^{[4
]}

D'Agostino, Jarod ^{[4
]}

Kaileh, Mary ^{[3
]}

Cui, Chang-Yi ^{[1
]}

Beerman, Isabel ^{[2
]}

Ferrucci, Luigi ^{[2
]}

Gorospe, Myriam ^{[1
]}

机构：

[1] NIA, Lab Genet & Genom, NIH, Intramural Res Program, Baltimore, MD 21224 USA

[2] NIA, Translat Gerontol Branch, NIH, Intramural Res Program, Baltimore, MD 21224 USA

[3] NIA, Lab Mol Biol & Immunol, NIH, Intramural Res Program, Baltimore, MD 21224 USA

[4] NIA, Clin Res Core, NIH, Intramural Res Program, Baltimore, MD 21224 USA

来源：

AGING CELL | 2022年 / 21卷 / 05期

基金：

美国国家卫生研究院;

关键词：

aging; autophagy; DNA damage; DNA repair; human dermal fibroblasts; proteomics; reactive oxygen species; ribosome biogenesis; FREE-RADICAL THEORY; SUPEROXIDE-DISMUTASE; RIBOSOME BIOGENESIS; STATISTICAL-MODEL; OXIDATIVE STRESS; DNA-DAMAGE; OVEREXPRESSION; AUTOPHAGY; PROTEINS; SENESCENCE;

D O I：

10.1111/acel.13609

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：18

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