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Deep proteome profiling reveals signatures of age and sex differences in paw skin and sciatic nerve of naïve mice

The age and sex of studied animals profoundly impact experimental outcomes in biomedical research. However, most preclinical studies in mice use a wide-spanning age range from 4 to 20 weeks and do not assess male and female mice in parallel. This raises concerns regarding reproducibility and neglect...

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Autores principales: Xian, Feng, Sondermann, Julia Regina, Gomez Varela, David, Schmidt, Manuela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9711526/
https://www.ncbi.nlm.nih.gov/pubmed/36448997
http://dx.doi.org/10.7554/eLife.81431
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author Xian, Feng
Sondermann, Julia Regina
Gomez Varela, David
Schmidt, Manuela
author_facet Xian, Feng
Sondermann, Julia Regina
Gomez Varela, David
Schmidt, Manuela
author_sort Xian, Feng
collection PubMed
description The age and sex of studied animals profoundly impact experimental outcomes in biomedical research. However, most preclinical studies in mice use a wide-spanning age range from 4 to 20 weeks and do not assess male and female mice in parallel. This raises concerns regarding reproducibility and neglects potentially relevant age and sex differences, which are largely unknown at the molecular level in naïve mice. Here, we employed an optimized quantitative proteomics workflow in order to deeply profile mouse paw skin and sciatic nerves (SCN) – two tissues implicated in nociception and pain as well as diseases linked to inflammation, injury, and demyelination. Remarkably, we uncovered significant differences when comparing male and female mice at adolescent (4 weeks) and adult (14 weeks) age. Our analysis deciphered protein subsets and networks that were correlated with the age and/or sex of mice. Notably, among these were proteins/biological pathways with known (patho)physiological relevance, e.g., homeostasis and epidermal signaling in skin, and, in SCN, multiple myelin proteins and regulators of neuronal development. Extensive comparisons with available databases revealed that various proteins associated with distinct skin diseases and pain exhibited significant abundance changes in dependence on age and/or sex. Taken together, our study uncovers hitherto unknown sex and age differences at the level of proteins and protein networks. Overall, we provide a unique proteome resource that facilitates mechanistic insights into somatosensory and skin biology, and integrates age and sex as biological variables – a prerequisite for successful preclinical studies in mouse disease models.
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spelling pubmed-97115262022-12-01 Deep proteome profiling reveals signatures of age and sex differences in paw skin and sciatic nerve of naïve mice Xian, Feng Sondermann, Julia Regina Gomez Varela, David Schmidt, Manuela eLife Computational and Systems Biology The age and sex of studied animals profoundly impact experimental outcomes in biomedical research. However, most preclinical studies in mice use a wide-spanning age range from 4 to 20 weeks and do not assess male and female mice in parallel. This raises concerns regarding reproducibility and neglects potentially relevant age and sex differences, which are largely unknown at the molecular level in naïve mice. Here, we employed an optimized quantitative proteomics workflow in order to deeply profile mouse paw skin and sciatic nerves (SCN) – two tissues implicated in nociception and pain as well as diseases linked to inflammation, injury, and demyelination. Remarkably, we uncovered significant differences when comparing male and female mice at adolescent (4 weeks) and adult (14 weeks) age. Our analysis deciphered protein subsets and networks that were correlated with the age and/or sex of mice. Notably, among these were proteins/biological pathways with known (patho)physiological relevance, e.g., homeostasis and epidermal signaling in skin, and, in SCN, multiple myelin proteins and regulators of neuronal development. Extensive comparisons with available databases revealed that various proteins associated with distinct skin diseases and pain exhibited significant abundance changes in dependence on age and/or sex. Taken together, our study uncovers hitherto unknown sex and age differences at the level of proteins and protein networks. Overall, we provide a unique proteome resource that facilitates mechanistic insights into somatosensory and skin biology, and integrates age and sex as biological variables – a prerequisite for successful preclinical studies in mouse disease models. eLife Sciences Publications, Ltd 2022-11-30 /pmc/articles/PMC9711526/ /pubmed/36448997 http://dx.doi.org/10.7554/eLife.81431 Text en © 2022, Xian, Sondermann et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Computational and Systems Biology
Xian, Feng
Sondermann, Julia Regina
Gomez Varela, David
Schmidt, Manuela
Deep proteome profiling reveals signatures of age and sex differences in paw skin and sciatic nerve of naïve mice
title Deep proteome profiling reveals signatures of age and sex differences in paw skin and sciatic nerve of naïve mice
title_full Deep proteome profiling reveals signatures of age and sex differences in paw skin and sciatic nerve of naïve mice
title_fullStr Deep proteome profiling reveals signatures of age and sex differences in paw skin and sciatic nerve of naïve mice
title_full_unstemmed Deep proteome profiling reveals signatures of age and sex differences in paw skin and sciatic nerve of naïve mice
title_short Deep proteome profiling reveals signatures of age and sex differences in paw skin and sciatic nerve of naïve mice
title_sort deep proteome profiling reveals signatures of age and sex differences in paw skin and sciatic nerve of naïve mice
topic Computational and Systems Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9711526/
https://www.ncbi.nlm.nih.gov/pubmed/36448997
http://dx.doi.org/10.7554/eLife.81431
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