Dataset Information

Human skin fibroblast proteome in healthy aging

ABSTRACT: The changes in the proteome of different human tissues with advancing age are poorly characterized. Here, we studied the proteins present in skin fibroblasts collected from 82 healthy individuals across a wide age spectrum (22 to 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 by linear regression models. Several differentially expressed proteins were implicated in processes that change with age, including autophagy, scavenging of reactive oxygen species (ROS), ribosome biogenesis, DNA replication, and DNA repair. Changes on these prominent pathways were further assessed using molecular and cell-culture approaches. Our study establishes a framework of the global proteome governing the homeostasis of the aged skin.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Myriam Gorospe

PROVIDER: MSV000088401 | MassIVE | Wed Nov 17 11:13:00 GMT 2021

SECONDARY ACCESSION(S): PXD029785

REPOSITORIES: MassIVE

ACCESS DATA

Publications

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

Tsitsipatis Dimitrios D Martindale Jennifer L JL Ubaida-Mohien Ceereena C Lyashkov Alexey A Yanai Hagai H Kashyap Amogh A Shin Chang Hoon CH Herman Allison B AB Ji Eunbyul E Yang Jen-Hao JH Munk Rachel R Dunn Christopher C Lukyanenko Yevgeniya Y Yang Xiaoling X Chia Chee W CW Karikkineth Ajoy C AC Zukley Linda L D'Agostino Jarod J Kaileh Mary M Cui Chang-Yi CY Beerman Isabel I Ferrucci Luigi L Gorospe Myriam M

Aging cell 20220415 5

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 spectro ...[more]

PMID: 35429111

Similar Datasets

Project description:Kollarovic2016 - Cell fate decision at G1-S transition This model is described in the article: To senesce or not to senesce: how primary human fibroblasts decide their cell fate after DNA damage. Kollarovic G, Studencka M, Ivanova L, Lauenstein C, Heinze K, Lapytsko A, Talemi SR, Figueiredo AS, Schaber J. Aging (Albany NY) 2016 Jan; Abstract: Excessive DNA damage can induce an irreversible cell cycle arrest, called senescence, which is generally perceived as an important tumour-suppressor mechanism. However, it is unclear how cells decide whether to senesce or not after DNA damage. By combining experimental data with a parameterized mathematical model we elucidate this cell fate decision at the G1-S transition. Our model provides a quantitative and conceptually new understanding of how human fibroblasts decide whether DNA damage is beyond repair and senesce. Model and data imply that the G1-S transition is regulated by a bistable hysteresis switch with respect to Cdk2 activity, which in turn is controlled by the Cdk2/p21 ratio rather than cyclin abundance. We experimentally confirm the resulting predictions that to induce senescence i) in healthy cells both high initial and elevated background DNA damage are necessary and sufficient, and ii) in already damaged cells much lower additional DNA damage is sufficient. Our study provides a mechanistic explanation of a) how noise in protein abundances allows cells to overcome the G1-S arrest even with substantial DNA damage, potentially leading to neoplasia, and b) how accumulating DNA damage with age increasingly sensitizes cells for senescence. This model is hosted on BioModels Database and identified by: BIOMD0000000632. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

Human skin fibroblast proteome in healthy aging

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure