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

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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

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Project description:Aging is characterized by a gradual decline in function, partly due to molecular damage that accumulates over time. Human skin is highly susceptible to both chronological aging and environmental damage in the form of UV photoaging. This results in detrimental structural and physiological changes with age. In this study we sought to comprehensively address both chronological and photoaging at the single-cell level, and to explore genetic and environmental factors, revealing their influences on the aging process. We included samples from young, middle-aged, and old individuals, and with these samples, we compared chronological aging and photoaging. Utilizing single-cell RNA sequencing, we created a comprehensive human skin cell atlas, that offers insights into the cellular composition and functions. We investigated the renewal ability of epidermis stem cells as they age and extended the study to fibroblasts, hair follicles, and endothelial cells. Examining the genetic landscape of aging in keratinocytes, we identified two distinct "gene modules" with altered gene expression during aging. Furthermore, we uncovered that skin aging involves interactions between epidermal keratinocytes and dermal fibroblasts, as well as extensive communication of keratinocytes with various other skin cell types as revealed through ligand-receptor pairs. Interactions, such as COL17A1-A1b1complex, highlighted a direct link between keratinocytes and fibroblast stimulation for collagen production. Most importantly, A key gene, MYO1, associated with skin aging was identified, leading to the development of an innovative mRNA treatment aimed at promoting skin rejuvenation by targeting this gene. Experimental results demonstrated that the mRNA treatment reduces basal stem cell senescence, increases basal stem cell proliferation, and enhances collagen production in fibroblasts via keratinocyte-fibroblast communication. The MYO1-targeted treatment is validated as an effective strategy for reversing skin aging by targeting cellular mechanisms.