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Updated: Jun 17, 2026
Determination of Fatty Acid Oxidation and Lipogenesis in Mouse Primary Hepatocytes
Published on: August 27, 2015
Lifespan-extending interventions induce consistent patterns of fatty acid oxidation in mouse livers
Kengo Watanabe1, Tomasz Wilmanski1, Priyanka Baloni2
1Institute for Systems Biology, Seattle, WA, USA.
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.
Insights
Multiple lifespan-extending interventions tighten biological regulation, particularly in fatty acid oxidation and immune response. Systems-level analysis reveals conserved molecular changes associated with longevity across diverse treatments.
Area of Science:
- Gerontology and Systems Biology
- Molecular Biology and Aging Research
Background:
- Aging is characterized by declining homeostasis and molecular dysregulation.
- Understanding aging requires systems-level investigation of biological processes.
Purpose of the Study:
- To investigate systemic molecular regulation changes under lifespan-extending interventions.
- To identify conserved and distinct regulatory patterns across different longevity interventions.
Main Methods:
- Differential Rank Conservation (DIRAC) analysis of mouse liver proteomics and transcriptomics data.
- Integration of transcriptomics data with a mouse genome-scale metabolic model.
Main Results:
- Mechanistically distinct interventions (acarbose, 17α-estradiol, rapamycin, calorie restriction) generally tighten biological module regulation.
- Conserved tightening patterns observed in fatty acid oxidation, immune response, and stress response modules.
- Discrepancies between protein and transcript DIRAC patterns suggest cap-independent translation's role.
Conclusions:
- Systems-level approaches effectively identify conserved molecular processes in aging and longevity.
- Lifespan-extending interventions converge on tightening regulatory networks, particularly in metabolic and immune pathways.
- Augmented cap-independent translation may contribute to conserved regulatory tightening.
