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

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.