Lifespan-extending interventions induce consistent patterns of fatty acid oxidation in mouse livers

Kengo Watanabe; Tomasz Wilmanski; Priyanka Baloni; Max Robinson; Gonzalo G. Garcia; Michael R. Hoopmann; Mukul K. Midha; David H. Baxter; Michal Maes; Seamus R. Morrone; Kelly M. Crebs; Charu Kapil; Ulrike Kusebauch; Jack Wiedrick; Jodi Lapidus; Lance Pflieger; Christopher Lausted; Jared C. Roach; Gwênlyn Glusman; Steven R. Cummings; Nicholas J. Schork; Nathan D. Price; Leroy Hood; Richard A. Miller; Robert L. Moritz; Noa Rappaport

doi:10.1038/s42003-023-05128-y

Lifespan-extending interventions induce consistent patterns of fatty acid oxidation in mouse livers

Kengo Watanabe, Tomasz Wilmanski, Priyanka Baloni, Max Robinson, Gonzalo G. Garcia, Michael R. Hoopmann, Mukul K. Midha, David H. Baxter, Michal Maes, Seamus R. Morrone, Kelly M. Crebs, Charu Kapil, Ulrike Kusebauch, Jack Wiedrick, Jodi Lapidus, Lance Pflieger, Christopher Lausted, Jared C. Roach, Gwênlyn Glusman, Steven R. CummingsNicholas J. Schork, Nathan D. Price, Leroy Hood, Richard A. Miller, Robert L. Moritz, Noa Rappaport

School Of Public Health

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

1 Scopus citations

Abstract

Aging manifests as progressive deteriorations in homeostasis, requiring systems-level perspectives to investigate the gradual molecular dysregulation of underlying biological processes. Here, we report systemic changes in the molecular regulation of biological processes under multiple lifespan-extending interventions. Differential Rank Conservation (DIRAC) analyses of mouse liver proteomics and transcriptomics data show that mechanistically distinct lifespan-extending interventions (acarbose, 17α-estradiol, rapamycin, and calorie restriction) generally tighten the regulation of biological modules. These tightening patterns are similar across the interventions, particularly in processes such as fatty acid oxidation, immune response, and stress response. Differences in DIRAC patterns between proteins and transcripts highlight specific modules which may be tightened via augmented cap-independent translation. Moreover, the systemic shifts in fatty acid metabolism are supported through integrated analysis of liver transcriptomics data with a mouse genome-scale metabolic model. Our findings highlight the power of systems-level approaches for identifying and characterizing the biological processes involved in aging and longevity.

Original language	English (US)
Article number	768
Journal	Communications Biology
Volume	6
Issue number	1
DOIs	https://doi.org/10.1038/s42003-023-05128-y
State	Published - Dec 2023

ASJC Scopus subject areas

Medicine (miscellaneous)
General Biochemistry, Genetics and Molecular Biology
General Agricultural and Biological Sciences

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Watanabe, K., Wilmanski, T., Baloni, P., Robinson, M., Garcia, G. G., Hoopmann, M. R., Midha, M. K., Baxter, D. H., Maes, M., Morrone, S. R., Crebs, K. M., Kapil, C., Kusebauch, U., Wiedrick, J., Lapidus, J., Pflieger, L., Lausted, C., Roach, J. C., Glusman, G., ... Rappaport, N. (2023). Lifespan-extending interventions induce consistent patterns of fatty acid oxidation in mouse livers. Communications Biology, 6(1), Article 768. https://doi.org/10.1038/s42003-023-05128-y

Watanabe, K, Wilmanski, T, Baloni, P, Robinson, M, Garcia, GG, Hoopmann, MR, Midha, MK, Baxter, DH, Maes, M, Morrone, SR, Crebs, KM, Kapil, C, Kusebauch, U, Wiedrick, J, Lapidus, J, Pflieger, L, Lausted, C, Roach, JC, Glusman, G, Cummings, SR, Schork, NJ, Price, ND, Hood, L, Miller, RA, Moritz, RL & Rappaport, N 2023, 'Lifespan-extending interventions induce consistent patterns of fatty acid oxidation in mouse livers', Communications Biology, vol. 6, no. 1, 768. https://doi.org/10.1038/s42003-023-05128-y

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abstract = "Aging manifests as progressive deteriorations in homeostasis, requiring systems-level perspectives to investigate the gradual molecular dysregulation of underlying biological processes. Here, we report systemic changes in the molecular regulation of biological processes under multiple lifespan-extending interventions. Differential Rank Conservation (DIRAC) analyses of mouse liver proteomics and transcriptomics data show that mechanistically distinct lifespan-extending interventions (acarbose, 17α-estradiol, rapamycin, and calorie restriction) generally tighten the regulation of biological modules. These tightening patterns are similar across the interventions, particularly in processes such as fatty acid oxidation, immune response, and stress response. Differences in DIRAC patterns between proteins and transcripts highlight specific modules which may be tightened via augmented cap-independent translation. Moreover, the systemic shifts in fatty acid metabolism are supported through integrated analysis of liver transcriptomics data with a mouse genome-scale metabolic model. Our findings highlight the power of systems-level approaches for identifying and characterizing the biological processes involved in aging and longevity.",

author = "Kengo Watanabe and Tomasz Wilmanski and Priyanka Baloni and Max Robinson and Garcia, {Gonzalo G.} and Hoopmann, {Michael R.} and Midha, {Mukul K.} and Baxter, {David H.} and Michal Maes and Morrone, {Seamus R.} and Crebs, {Kelly M.} and Charu Kapil and Ulrike Kusebauch and Jack Wiedrick and Jodi Lapidus and Lance Pflieger and Christopher Lausted and Roach, {Jared C.} and Gw{\^e}nlyn Glusman and Cummings, {Steven R.} and Schork, {Nicholas J.} and Price, {Nathan D.} and Leroy Hood and Miller, {Richard A.} and Moritz, {Robert L.} and Noa Rappaport",

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AU - Baloni, Priyanka

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AU - Garcia, Gonzalo G.

AU - Hoopmann, Michael R.

AU - Midha, Mukul K.

AU - Baxter, David H.

AU - Maes, Michal

AU - Morrone, Seamus R.

AU - Crebs, Kelly M.

AU - Kapil, Charu

AU - Kusebauch, Ulrike

AU - Wiedrick, Jack

AU - Lapidus, Jodi

AU - Pflieger, Lance

AU - Lausted, Christopher

AU - Roach, Jared C.

AU - Glusman, Gwênlyn

AU - Cummings, Steven R.

AU - Schork, Nicholas J.

AU - Price, Nathan D.

AU - Hood, Leroy

AU - Miller, Richard A.

AU - Moritz, Robert L.

AU - Rappaport, Noa

PY - 2023/12

Y1 - 2023/12

N2 - Aging manifests as progressive deteriorations in homeostasis, requiring systems-level perspectives to investigate the gradual molecular dysregulation of underlying biological processes. Here, we report systemic changes in the molecular regulation of biological processes under multiple lifespan-extending interventions. Differential Rank Conservation (DIRAC) analyses of mouse liver proteomics and transcriptomics data show that mechanistically distinct lifespan-extending interventions (acarbose, 17α-estradiol, rapamycin, and calorie restriction) generally tighten the regulation of biological modules. These tightening patterns are similar across the interventions, particularly in processes such as fatty acid oxidation, immune response, and stress response. Differences in DIRAC patterns between proteins and transcripts highlight specific modules which may be tightened via augmented cap-independent translation. Moreover, the systemic shifts in fatty acid metabolism are supported through integrated analysis of liver transcriptomics data with a mouse genome-scale metabolic model. Our findings highlight the power of systems-level approaches for identifying and characterizing the biological processes involved in aging and longevity.

AB - Aging manifests as progressive deteriorations in homeostasis, requiring systems-level perspectives to investigate the gradual molecular dysregulation of underlying biological processes. Here, we report systemic changes in the molecular regulation of biological processes under multiple lifespan-extending interventions. Differential Rank Conservation (DIRAC) analyses of mouse liver proteomics and transcriptomics data show that mechanistically distinct lifespan-extending interventions (acarbose, 17α-estradiol, rapamycin, and calorie restriction) generally tighten the regulation of biological modules. These tightening patterns are similar across the interventions, particularly in processes such as fatty acid oxidation, immune response, and stress response. Differences in DIRAC patterns between proteins and transcripts highlight specific modules which may be tightened via augmented cap-independent translation. Moreover, the systemic shifts in fatty acid metabolism are supported through integrated analysis of liver transcriptomics data with a mouse genome-scale metabolic model. Our findings highlight the power of systems-level approaches for identifying and characterizing the biological processes involved in aging and longevity.

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Lifespan-extending interventions induce consistent patterns of fatty acid oxidation in mouse livers

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