Ether lipids and sphingolipids drive sex-specific human aging dynamics.

Area of Science:

• Gerontology
• Metabolomics
• Lipidomics

Background:

• Aging involves complex molecular changes, including alterations in lipid metabolism.
• Understanding age-related lipidome dynamics and sex-specific signatures is crucial for healthy aging research.

Purpose of the Study:

• To systematically define lipidome dynamics across the lifespan.
• To identify sex-specific lipidomic signatures associated with aging.
• To investigate the functional implications of age-related lipid shifts.

Main Methods:

• Targeted lipidomic profiling of plasma from 1030 adults (aged 50-98 years).
• Analysis of 543 lipid species and circulating fatty acid composition using mass spectrometry and gas chromatography.
• Identification of age-related lipidomic shifts and sex-specific patterns.

Main Results:

• Significant age-related shifts in lipid metabolism were observed, particularly affecting ceramides and ether-linked phospholipids.
• Three distinct aging crests were identified (55-60, 65-70, 75-80 years), with sex-specific dominance in the 65-70 (men) and 75-80 (women) year crests.
• Lipid enrichment analysis revealed acylcarnitines, sphingolipids, and ether-linked phospholipids as key contributors, indicating impaired lipid functional categories.

Conclusions:

• Lipid metabolism exhibits non-linear dynamics during aging, with functional impairments in bioenergetics, antioxidant defense, and signaling.
• The study provides a comprehensive map of age-related lipidomic changes and sex-specific variations.
• Findings lay the groundwork for developing biomarkers and interventions to promote healthy aging.