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 E. 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 Karikkineth, Linda Zukley, Jarod D’Agostino, Mary Kaileh, Chang‐Yi Cui, Isabel Beerman, Luigi Ferrucci, Myriam Gorospe
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.