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Comparative Study of Protein Aggregation Propensity and Mutation Tolerance Between Naked Mole-Rat and Mouse
The molecular mechanisms of aging and life expectancy have been studied in model organisms with short lifespans. However, long-lived species may provide insights into successful strategies for healthy aging, potentially opening the door for novel therapeutic interventions in age-related diseases. No...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086952/ https://www.ncbi.nlm.nih.gov/pubmed/35482036 http://dx.doi.org/10.1093/gbe/evac057 |
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author | Besse, Savandara Poujol, Raphaël Hussin, Julie G. |
author_facet | Besse, Savandara Poujol, Raphaël Hussin, Julie G. |
author_sort | Besse, Savandara |
collection | PubMed |
description | The molecular mechanisms of aging and life expectancy have been studied in model organisms with short lifespans. However, long-lived species may provide insights into successful strategies for healthy aging, potentially opening the door for novel therapeutic interventions in age-related diseases. Notably, naked mole-rats, the longest-lived rodent, present attenuated aging phenotypes compared with mice. Their resistance toward oxidative stress has been proposed as one hallmark of their healthy aging, suggesting their ability to maintain cell homeostasis, specifically their protein homeostasis. To identify the general principles behind their protein homeostasis robustness, we compared the aggregation propensity and mutation tolerance of naked mole-rat and mouse orthologous proteins. Our analysis showed no proteome-wide differential effects in aggregation propensity and mutation tolerance between these species, but several subsets of proteins with a significant difference in aggregation propensity. We found an enrichment of proteins with higher aggregation propensity in naked mole-rat, and these are functionally involved in the inflammasome complex and nucleic acid binding. On the other hand, proteins with lower aggregation propensity in naked mole-rat have a significantly higher mutation tolerance compared with the rest of the proteins. Among them, we identified proteins known to be associated with neurodegenerative and age-related diseases. These findings highlight the intriguing hypothesis about the capacity of the naked mole-rat proteome to delay aging through its proteomic intrinsic architecture. |
format | Online Article Text |
id | pubmed-9086952 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-90869522022-05-11 Comparative Study of Protein Aggregation Propensity and Mutation Tolerance Between Naked Mole-Rat and Mouse Besse, Savandara Poujol, Raphaël Hussin, Julie G. Genome Biol Evol Research Article The molecular mechanisms of aging and life expectancy have been studied in model organisms with short lifespans. However, long-lived species may provide insights into successful strategies for healthy aging, potentially opening the door for novel therapeutic interventions in age-related diseases. Notably, naked mole-rats, the longest-lived rodent, present attenuated aging phenotypes compared with mice. Their resistance toward oxidative stress has been proposed as one hallmark of their healthy aging, suggesting their ability to maintain cell homeostasis, specifically their protein homeostasis. To identify the general principles behind their protein homeostasis robustness, we compared the aggregation propensity and mutation tolerance of naked mole-rat and mouse orthologous proteins. Our analysis showed no proteome-wide differential effects in aggregation propensity and mutation tolerance between these species, but several subsets of proteins with a significant difference in aggregation propensity. We found an enrichment of proteins with higher aggregation propensity in naked mole-rat, and these are functionally involved in the inflammasome complex and nucleic acid binding. On the other hand, proteins with lower aggregation propensity in naked mole-rat have a significantly higher mutation tolerance compared with the rest of the proteins. Among them, we identified proteins known to be associated with neurodegenerative and age-related diseases. These findings highlight the intriguing hypothesis about the capacity of the naked mole-rat proteome to delay aging through its proteomic intrinsic architecture. Oxford University Press 2022-04-28 /pmc/articles/PMC9086952/ /pubmed/35482036 http://dx.doi.org/10.1093/gbe/evac057 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Besse, Savandara Poujol, Raphaël Hussin, Julie G. Comparative Study of Protein Aggregation Propensity and Mutation Tolerance Between Naked Mole-Rat and Mouse |
title | Comparative Study of Protein Aggregation Propensity and Mutation Tolerance Between Naked Mole-Rat and Mouse |
title_full | Comparative Study of Protein Aggregation Propensity and Mutation Tolerance Between Naked Mole-Rat and Mouse |
title_fullStr | Comparative Study of Protein Aggregation Propensity and Mutation Tolerance Between Naked Mole-Rat and Mouse |
title_full_unstemmed | Comparative Study of Protein Aggregation Propensity and Mutation Tolerance Between Naked Mole-Rat and Mouse |
title_short | Comparative Study of Protein Aggregation Propensity and Mutation Tolerance Between Naked Mole-Rat and Mouse |
title_sort | comparative study of protein aggregation propensity and mutation tolerance between naked mole-rat and mouse |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086952/ https://www.ncbi.nlm.nih.gov/pubmed/35482036 http://dx.doi.org/10.1093/gbe/evac057 |
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