A class of anti-inflammatory lipids decrease with aging in the central nervous system

Dan Tan; Srihari Konduri; Meric Erikci Ertunc; Pan Zhang; Justin Wang; Tina Chang; Antonio F.M. Pinto; Andrea Rocha; Cynthia J. Donaldson; Joan M. Vaughan; Raissa G. Ludwig; Elizabeth Willey; Manasi Iyer; Peter C. Gray; Pamela Maher; Nicola J. Allen; J. Bradley Zuchero; Andrew Dillin; Marcelo A. Mori; Steven G. Kohama; Dionicio Siegel; Alan Saghatelian

doi:10.1038/s41589-022-01165-6

A class of anti-inflammatory lipids decrease with aging in the central nervous system

Dan Tan, Srihari Konduri, Meric Erikci Ertunc, Pan Zhang, Justin Wang, Tina Chang, Antonio F.M. Pinto, Andrea Rocha, Cynthia J. Donaldson, Joan M. Vaughan, Raissa G. Ludwig, Elizabeth Willey, Manasi Iyer, Peter C. Gray, Pamela Maher, Nicola J. Allen, J. Bradley Zuchero, Andrew Dillin, Marcelo A. Mori, Steven G. KohamaDionicio Siegel, Alan Saghatelian

Oregon National Primate Research Center

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Lipids contribute to the structure, development, and function of healthy brains. Dysregulated lipid metabolism is linked to aging and diseased brains. However, our understanding of lipid metabolism in aging brains remains limited. Here we examined the brain lipidome of mice across their lifespan using untargeted lipidomics. Co-expression network analysis highlighted a progressive decrease in 3-sulfogalactosyl diacylglycerols (SGDGs) and SGDG pathway members, including the potential degradation products lyso-SGDGs. SGDGs show an age-related decline specifically in the central nervous system and are associated with myelination. We also found that an SGDG dramatically suppresses LPS-induced gene expression and release of pro-inflammatory cytokines from macrophages and microglia by acting on the NF-κB pathway. The detection of SGDGs in human and macaque brains establishes their evolutionary conservation. This work enhances interest in SGDGs regarding their roles in aging and inflammatory diseases and highlights the complexity of the brain lipidome and potential biological functions in aging. [Figure not available: see fulltext.]

Original language	English (US)
Pages (from-to)	187-197
Number of pages	11
Journal	Nature Chemical Biology
Volume	19
Issue number	2
DOIs	https://doi.org/10.1038/s41589-022-01165-6
State	Published - Feb 2023

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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Tan, D., Konduri, S., Erikci Ertunc, M., Zhang, P., Wang, J., Chang, T., Pinto, A. F. M., Rocha, A., Donaldson, C. J., Vaughan, J. M., Ludwig, R. G., Willey, E., Iyer, M., Gray, P. C., Maher, P., Allen, N. J., Zuchero, J. B., Dillin, A., Mori, M. A., ... Saghatelian, A. (2023). A class of anti-inflammatory lipids decrease with aging in the central nervous system. Nature Chemical Biology, 19(2), 187-197. https://doi.org/10.1038/s41589-022-01165-6

Tan, D, Konduri, S, Erikci Ertunc, M, Zhang, P, Wang, J, Chang, T, Pinto, AFM, Rocha, A, Donaldson, CJ, Vaughan, JM, Ludwig, RG, Willey, E, Iyer, M, Gray, PC, Maher, P, Allen, NJ, Zuchero, JB, Dillin, A, Mori, MA, Kohama, SG, Siegel, D & Saghatelian, A 2023, 'A class of anti-inflammatory lipids decrease with aging in the central nervous system', Nature Chemical Biology, vol. 19, no. 2, pp. 187-197. https://doi.org/10.1038/s41589-022-01165-6

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title = "A class of anti-inflammatory lipids decrease with aging in the central nervous system",

abstract = "Lipids contribute to the structure, development, and function of healthy brains. Dysregulated lipid metabolism is linked to aging and diseased brains. However, our understanding of lipid metabolism in aging brains remains limited. Here we examined the brain lipidome of mice across their lifespan using untargeted lipidomics. Co-expression network analysis highlighted a progressive decrease in 3-sulfogalactosyl diacylglycerols (SGDGs) and SGDG pathway members, including the potential degradation products lyso-SGDGs. SGDGs show an age-related decline specifically in the central nervous system and are associated with myelination. We also found that an SGDG dramatically suppresses LPS-induced gene expression and release of pro-inflammatory cytokines from macrophages and microglia by acting on the NF-κB pathway. The detection of SGDGs in human and macaque brains establishes their evolutionary conservation. This work enhances interest in SGDGs regarding their roles in aging and inflammatory diseases and highlights the complexity of the brain lipidome and potential biological functions in aging. [Figure not available: see fulltext.]",

author = "Dan Tan and Srihari Konduri and {Erikci Ertunc}, Meric and Pan Zhang and Justin Wang and Tina Chang and Pinto, {Antonio F.M.} and Andrea Rocha and Donaldson, {Cynthia J.} and Vaughan, {Joan M.} and Ludwig, {Raissa G.} and Elizabeth Willey and Manasi Iyer and Gray, {Peter C.} and Pamela Maher and Allen, {Nicola J.} and Zuchero, {J. Bradley} and Andrew Dillin and Mori, {Marcelo A.} and Kohama, {Steven G.} and Dionicio Siegel and Alan Saghatelian",

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AU - Konduri, Srihari

AU - Erikci Ertunc, Meric

AU - Zhang, Pan

AU - Wang, Justin

AU - Chang, Tina

AU - Pinto, Antonio F.M.

AU - Rocha, Andrea

AU - Donaldson, Cynthia J.

AU - Vaughan, Joan M.

AU - Ludwig, Raissa G.

AU - Willey, Elizabeth

AU - Iyer, Manasi

AU - Gray, Peter C.

AU - Maher, Pamela

AU - Allen, Nicola J.

AU - Zuchero, J. Bradley

AU - Dillin, Andrew

AU - Mori, Marcelo A.

AU - Kohama, Steven G.

AU - Siegel, Dionicio

AU - Saghatelian, Alan

PY - 2023/2

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N2 - Lipids contribute to the structure, development, and function of healthy brains. Dysregulated lipid metabolism is linked to aging and diseased brains. However, our understanding of lipid metabolism in aging brains remains limited. Here we examined the brain lipidome of mice across their lifespan using untargeted lipidomics. Co-expression network analysis highlighted a progressive decrease in 3-sulfogalactosyl diacylglycerols (SGDGs) and SGDG pathway members, including the potential degradation products lyso-SGDGs. SGDGs show an age-related decline specifically in the central nervous system and are associated with myelination. We also found that an SGDG dramatically suppresses LPS-induced gene expression and release of pro-inflammatory cytokines from macrophages and microglia by acting on the NF-κB pathway. The detection of SGDGs in human and macaque brains establishes their evolutionary conservation. This work enhances interest in SGDGs regarding their roles in aging and inflammatory diseases and highlights the complexity of the brain lipidome and potential biological functions in aging. [Figure not available: see fulltext.]

AB - Lipids contribute to the structure, development, and function of healthy brains. Dysregulated lipid metabolism is linked to aging and diseased brains. However, our understanding of lipid metabolism in aging brains remains limited. Here we examined the brain lipidome of mice across their lifespan using untargeted lipidomics. Co-expression network analysis highlighted a progressive decrease in 3-sulfogalactosyl diacylglycerols (SGDGs) and SGDG pathway members, including the potential degradation products lyso-SGDGs. SGDGs show an age-related decline specifically in the central nervous system and are associated with myelination. We also found that an SGDG dramatically suppresses LPS-induced gene expression and release of pro-inflammatory cytokines from macrophages and microglia by acting on the NF-κB pathway. The detection of SGDGs in human and macaque brains establishes their evolutionary conservation. This work enhances interest in SGDGs regarding their roles in aging and inflammatory diseases and highlights the complexity of the brain lipidome and potential biological functions in aging. [Figure not available: see fulltext.]

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A class of anti-inflammatory lipids decrease with aging in the central nervous system

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