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Aging hallmarks exhibit organ-specific temporal signatures

Aging is the single greatest cause of disease and death worldwide, and understanding the associated processes could vastly improve quality of life. While the field has identified major categories of aging damage such as altered intercellular communication, loss of proteostasis, and eroded mitochondr...

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Autores principales: Schaum, Nicholas, Lehallier, Benoit, Hahn, Oliver, Pálovics, Róbert, Hosseinzadeh, Shayan, Lee, Song E., Sit, Rene, Lee, Davis P., Losada, Patricia Morán, Zardeneta, Macy E., Fehlmann, Tobias, Webber, James, McGeever, Aaron, Calcuttawala, Kruti, Zhang, Hui, Berdnik, Daniela, Mathur, Vidhu, Tan, Weilun, Zee, Alexander, Tan, Michelle, Pisco, Angela, Karkanias, Jim, Neff, Norma F., Keller, Andreas, Darmanis, Spyros, Quake, Stephen R., Wyss-Coray, Tony
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757734/
https://www.ncbi.nlm.nih.gov/pubmed/32669715
http://dx.doi.org/10.1038/s41586-020-2499-y
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author Schaum, Nicholas
Lehallier, Benoit
Hahn, Oliver
Pálovics, Róbert
Hosseinzadeh, Shayan
Lee, Song E.
Sit, Rene
Lee, Davis P.
Losada, Patricia Morán
Zardeneta, Macy E.
Fehlmann, Tobias
Webber, James
McGeever, Aaron
Calcuttawala, Kruti
Zhang, Hui
Berdnik, Daniela
Mathur, Vidhu
Tan, Weilun
Zee, Alexander
Tan, Michelle
Pisco, Angela
Karkanias, Jim
Neff, Norma F.
Keller, Andreas
Darmanis, Spyros
Quake, Stephen R.
Wyss-Coray, Tony
author_facet Schaum, Nicholas
Lehallier, Benoit
Hahn, Oliver
Pálovics, Róbert
Hosseinzadeh, Shayan
Lee, Song E.
Sit, Rene
Lee, Davis P.
Losada, Patricia Morán
Zardeneta, Macy E.
Fehlmann, Tobias
Webber, James
McGeever, Aaron
Calcuttawala, Kruti
Zhang, Hui
Berdnik, Daniela
Mathur, Vidhu
Tan, Weilun
Zee, Alexander
Tan, Michelle
Pisco, Angela
Karkanias, Jim
Neff, Norma F.
Keller, Andreas
Darmanis, Spyros
Quake, Stephen R.
Wyss-Coray, Tony
author_sort Schaum, Nicholas
collection PubMed
description Aging is the single greatest cause of disease and death worldwide, and understanding the associated processes could vastly improve quality of life. While the field has identified major categories of aging damage such as altered intercellular communication, loss of proteostasis, and eroded mitochondrial function(1), these deleterious processes interact with extraordinary complexity within and between organs. Yet, a comprehensive analysis of aging dynamics organism-wide has been lacking. Here we performed bulk RNA-sequencing of 17 organs and plasma proteomics at 10 ages across the mouse lifespan, and integrated these findings with data from the companion Tabula Muris Senis(2,3). We uncover previously unknown linear and non-linear expression shifts during aging, which cluster in strikingly consistent trajectory groups with coherent biological functions, including extracellular matrix regulation, unfolded protein binding, mitochondrial function, and inflammatory and immune response. Remarkably, these gene sets are expressed similarly across tissues, differing merely in age of onset and amplitude. Widespread immune cell activation is especially pronounced and first detectable in white adipose depots during middle age. Single-cell RNA-sequencing confirms the accumulation of adipose T and B cells, including immunoglobulin J-expressing plasma cells, which also accrue concurrently across diverse organs. Finally, we show how expression shifts in distinct tissues are highly correlated with corresponding protein levels in plasma, thus potentially contributing to aging of the systemic circulation. Together, these data demonstrate a similar yet asynchronous inter- and intra-organ progression of aging, thereby providing a foundation to track systemic sources of declining health at old age.
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spelling pubmed-77577342021-01-15 Aging hallmarks exhibit organ-specific temporal signatures Schaum, Nicholas Lehallier, Benoit Hahn, Oliver Pálovics, Róbert Hosseinzadeh, Shayan Lee, Song E. Sit, Rene Lee, Davis P. Losada, Patricia Morán Zardeneta, Macy E. Fehlmann, Tobias Webber, James McGeever, Aaron Calcuttawala, Kruti Zhang, Hui Berdnik, Daniela Mathur, Vidhu Tan, Weilun Zee, Alexander Tan, Michelle Pisco, Angela Karkanias, Jim Neff, Norma F. Keller, Andreas Darmanis, Spyros Quake, Stephen R. Wyss-Coray, Tony Nature Article Aging is the single greatest cause of disease and death worldwide, and understanding the associated processes could vastly improve quality of life. While the field has identified major categories of aging damage such as altered intercellular communication, loss of proteostasis, and eroded mitochondrial function(1), these deleterious processes interact with extraordinary complexity within and between organs. Yet, a comprehensive analysis of aging dynamics organism-wide has been lacking. Here we performed bulk RNA-sequencing of 17 organs and plasma proteomics at 10 ages across the mouse lifespan, and integrated these findings with data from the companion Tabula Muris Senis(2,3). We uncover previously unknown linear and non-linear expression shifts during aging, which cluster in strikingly consistent trajectory groups with coherent biological functions, including extracellular matrix regulation, unfolded protein binding, mitochondrial function, and inflammatory and immune response. Remarkably, these gene sets are expressed similarly across tissues, differing merely in age of onset and amplitude. Widespread immune cell activation is especially pronounced and first detectable in white adipose depots during middle age. Single-cell RNA-sequencing confirms the accumulation of adipose T and B cells, including immunoglobulin J-expressing plasma cells, which also accrue concurrently across diverse organs. Finally, we show how expression shifts in distinct tissues are highly correlated with corresponding protein levels in plasma, thus potentially contributing to aging of the systemic circulation. Together, these data demonstrate a similar yet asynchronous inter- and intra-organ progression of aging, thereby providing a foundation to track systemic sources of declining health at old age. 2020-07-15 2020-07 /pmc/articles/PMC7757734/ /pubmed/32669715 http://dx.doi.org/10.1038/s41586-020-2499-y Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms Author Information Reprints and permissions information is available at www.nature.com/reprints (http://www.nature.com/reprints) . Readers are welcome to comment on the online version of the paper.
spellingShingle Article
Schaum, Nicholas
Lehallier, Benoit
Hahn, Oliver
Pálovics, Róbert
Hosseinzadeh, Shayan
Lee, Song E.
Sit, Rene
Lee, Davis P.
Losada, Patricia Morán
Zardeneta, Macy E.
Fehlmann, Tobias
Webber, James
McGeever, Aaron
Calcuttawala, Kruti
Zhang, Hui
Berdnik, Daniela
Mathur, Vidhu
Tan, Weilun
Zee, Alexander
Tan, Michelle
Pisco, Angela
Karkanias, Jim
Neff, Norma F.
Keller, Andreas
Darmanis, Spyros
Quake, Stephen R.
Wyss-Coray, Tony
Aging hallmarks exhibit organ-specific temporal signatures
title Aging hallmarks exhibit organ-specific temporal signatures
title_full Aging hallmarks exhibit organ-specific temporal signatures
title_fullStr Aging hallmarks exhibit organ-specific temporal signatures
title_full_unstemmed Aging hallmarks exhibit organ-specific temporal signatures
title_short Aging hallmarks exhibit organ-specific temporal signatures
title_sort aging hallmarks exhibit organ-specific temporal signatures
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757734/
https://www.ncbi.nlm.nih.gov/pubmed/32669715
http://dx.doi.org/10.1038/s41586-020-2499-y
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